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Canakinumab (Ilaris) tapering tested in systemic JIA trial
A trial that tested two ways of tapering canakinumab (Ilaris) monotherapy in children with systemic juvenile idiopathic arthritis (sJIA) showed that both approaches might be feasible, but the lack of a control arm means that more data are needed before putting either into routine clinical practice.
Pierre Quartier, MD, and associates reported in Arthritis & Rheumatology. That’s with the proviso that children are taking canakinumab at the recommended dose of 4 mg/kg every 4 weeks and achieve clinical remission before any tapering is started.
The researchers found that 70%-80% of children who were in complete clinical remission (CR) maintained this for 6 months after the first dose-tapering step had been taken. However, at least one-fifth of study participants experienced a disease flare during treatment withdrawal, and only one-third were able to discontinue treatment altogether, which suggests continued treatment is needed.
“The results are a step in the right direction,” commented Athimaleipet Ramanan, MBBS, a consultant pediatric rheumatologist who was not involved in the study. They “offer the first vision of whether we can actually taper a medication” in sJIA because “until now we have not had any evidence for this,” he added.
“What we really need to know, which the study doesn’t tell you, is: Is decreasing the dose better than stopping?” said Dr. Ramanan, of the Bristol (England) Royal Hospital for Children.
Another thing that is important to know is: Does reducing the dose lead to the development of anti-drug antibodies? he said.
“There were some concerns that, when you give less of a monoclonal antibody, you might get more neutralizing anti-drug antibodies or you might make a drug more immunogenic,” he said. These data perhaps suggest that this isn’t the case because only one child on one occasion had detectable non-neutralizing anti-drug antibodies during the entire study, and that was 11 weeks after the last dose of canakinumab had been given.
Study results and design
Canakinumab is a monoclonal antibody that inhibits interleukin-1 (IL-1) that has been approved in the United States and Europe for the treatment of sJIA since 2013. Reducing a child’s exposure to canakinumab once their disease is under control is an attractive proposition given the treat-to-target approach used increasingly throughout modern rheumatologic practice. It could also help reduce the cost of what is an expensive treatment, compared with other available options for sJIA such as the interleukin-6 inhibitor tocilizumab (Actemra) or another IL-1 inhibitor anakinra (Kineret), which is not FDA-approved for use in sJIA and requires weekly injections.
“We don’t want to the disease to reappear, to flare, but we also don’t want to overuse treatments in these patients,” explained Dr. Quartier of Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris in an interview.
The study he coconducted, given the acronym B-SPECIFIC-4 Patients, was an open-label study that consisted of two parts. In part 1, 182 children were given subcutaneous canakinumab 4 mg/kg every 4 weeks. In part 2, 76 children who were in complete CR after canakinumab treatment were randomized to one of two tapering strategies. In one arm, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg given every 4 weeks before eventually discontinuing treatment, and in other arm the duration between dosing was increased by 4-week intervals, from 4 to 8 weeks, then 12 weeks, then discontinuation.
If children were taking glucocorticoids or methotrexate, the treating physicians were encouraged to stop these medications if possible, with 34%-39% and 42%-59% of children, respectively, being able to do so. The rate depended on whether children had received canakinumab before entering the study because some had been recruited from a long-term extension study while others were naive to the biologic; all had inactive disease at study entry.
This was the first study to evaluate the effectiveness of canakinumab in enabling the discontinuation of methotrexate, but the primary objective was to assess whether more than 40% of randomized patients in either discontinuation arm remained in CR for 24 weeks after the first step of discontinuation. This was achieved in 71% of children who were in the dose-reduction arm and in 84% of children in the dose-prolongation arm (P ≤ .0001 for each arm vs. 40%).
Prior exposure to canakinumab did not seem to affect the maintenance of CR, but it was also found that more children who maintained CR at their second but not their first attempt at tapering were in CR than those who were still in CR at the first step (76% and 89% in the dose-reduction and dose-prolongation arms, respectively).
Among the two dosing regimens, failure occurred in 18% of children in the dose-reduction arm at the first step, 10% at the second, and 8% at the third, whereas 2.7% of children in the dose-prolongation arm experienced regimen failure at the first step, 6.1% at the second, and 15% at the third.
No substantial difference between the two tapering approaches was observed because the study was not powered to look at this. There was also no control arm, such as a group continuing treatment while the other groups tapered, or as Dr. Ramanan had pointed out, stopping canakinumab altogether.
“As long as the treatment was continued, even at very low dosage, most patients remained in inactive disease,” Dr. Quartier said. He added, however, that only a minority of patients could stop treatment completely. Treatment should not be stopped abruptly, he advised, because this was associated with a substantial number of disease flares that needed treatment to be reinstated.
These findings suggest that “a certain level of sustained inhibition of the IL-1 pathway seems important for the maintenance of CR in most sJIA patients,” Dr. Quartier and coinvestigators wrote in their article.
They added: “We believe that these results are relevant for clinical practice, particularly for designing personalized tapering strategies that can allow an adequate control of disease while minimizing the side effects of certain medications, notably glucocorticoids.”
The study was funded by Novartis in collaboration with the Pediatric Rheumatology International Trials Organization and the Pediatric Rheumatology Collaborative Study Group. Dr. Quartier was an investigator for the trial and has received research and consultancy fees from Novartis, among other pharmaceutical companies. Two of his coauthors are employees of Novartis. Dr. Ramanan has acted as an investigator in prior canakinumab trials and has received consultancy fees from Novartis and multiple other companies.
SOURCE: Quartier P et al. Arthritis Rheumatol. 2020 Aug 11. doi: 10.1002/art.41488.
A trial that tested two ways of tapering canakinumab (Ilaris) monotherapy in children with systemic juvenile idiopathic arthritis (sJIA) showed that both approaches might be feasible, but the lack of a control arm means that more data are needed before putting either into routine clinical practice.
Pierre Quartier, MD, and associates reported in Arthritis & Rheumatology. That’s with the proviso that children are taking canakinumab at the recommended dose of 4 mg/kg every 4 weeks and achieve clinical remission before any tapering is started.
The researchers found that 70%-80% of children who were in complete clinical remission (CR) maintained this for 6 months after the first dose-tapering step had been taken. However, at least one-fifth of study participants experienced a disease flare during treatment withdrawal, and only one-third were able to discontinue treatment altogether, which suggests continued treatment is needed.
“The results are a step in the right direction,” commented Athimaleipet Ramanan, MBBS, a consultant pediatric rheumatologist who was not involved in the study. They “offer the first vision of whether we can actually taper a medication” in sJIA because “until now we have not had any evidence for this,” he added.
“What we really need to know, which the study doesn’t tell you, is: Is decreasing the dose better than stopping?” said Dr. Ramanan, of the Bristol (England) Royal Hospital for Children.
Another thing that is important to know is: Does reducing the dose lead to the development of anti-drug antibodies? he said.
“There were some concerns that, when you give less of a monoclonal antibody, you might get more neutralizing anti-drug antibodies or you might make a drug more immunogenic,” he said. These data perhaps suggest that this isn’t the case because only one child on one occasion had detectable non-neutralizing anti-drug antibodies during the entire study, and that was 11 weeks after the last dose of canakinumab had been given.
Study results and design
Canakinumab is a monoclonal antibody that inhibits interleukin-1 (IL-1) that has been approved in the United States and Europe for the treatment of sJIA since 2013. Reducing a child’s exposure to canakinumab once their disease is under control is an attractive proposition given the treat-to-target approach used increasingly throughout modern rheumatologic practice. It could also help reduce the cost of what is an expensive treatment, compared with other available options for sJIA such as the interleukin-6 inhibitor tocilizumab (Actemra) or another IL-1 inhibitor anakinra (Kineret), which is not FDA-approved for use in sJIA and requires weekly injections.
“We don’t want to the disease to reappear, to flare, but we also don’t want to overuse treatments in these patients,” explained Dr. Quartier of Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris in an interview.
The study he coconducted, given the acronym B-SPECIFIC-4 Patients, was an open-label study that consisted of two parts. In part 1, 182 children were given subcutaneous canakinumab 4 mg/kg every 4 weeks. In part 2, 76 children who were in complete CR after canakinumab treatment were randomized to one of two tapering strategies. In one arm, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg given every 4 weeks before eventually discontinuing treatment, and in other arm the duration between dosing was increased by 4-week intervals, from 4 to 8 weeks, then 12 weeks, then discontinuation.
If children were taking glucocorticoids or methotrexate, the treating physicians were encouraged to stop these medications if possible, with 34%-39% and 42%-59% of children, respectively, being able to do so. The rate depended on whether children had received canakinumab before entering the study because some had been recruited from a long-term extension study while others were naive to the biologic; all had inactive disease at study entry.
This was the first study to evaluate the effectiveness of canakinumab in enabling the discontinuation of methotrexate, but the primary objective was to assess whether more than 40% of randomized patients in either discontinuation arm remained in CR for 24 weeks after the first step of discontinuation. This was achieved in 71% of children who were in the dose-reduction arm and in 84% of children in the dose-prolongation arm (P ≤ .0001 for each arm vs. 40%).
Prior exposure to canakinumab did not seem to affect the maintenance of CR, but it was also found that more children who maintained CR at their second but not their first attempt at tapering were in CR than those who were still in CR at the first step (76% and 89% in the dose-reduction and dose-prolongation arms, respectively).
Among the two dosing regimens, failure occurred in 18% of children in the dose-reduction arm at the first step, 10% at the second, and 8% at the third, whereas 2.7% of children in the dose-prolongation arm experienced regimen failure at the first step, 6.1% at the second, and 15% at the third.
No substantial difference between the two tapering approaches was observed because the study was not powered to look at this. There was also no control arm, such as a group continuing treatment while the other groups tapered, or as Dr. Ramanan had pointed out, stopping canakinumab altogether.
“As long as the treatment was continued, even at very low dosage, most patients remained in inactive disease,” Dr. Quartier said. He added, however, that only a minority of patients could stop treatment completely. Treatment should not be stopped abruptly, he advised, because this was associated with a substantial number of disease flares that needed treatment to be reinstated.
These findings suggest that “a certain level of sustained inhibition of the IL-1 pathway seems important for the maintenance of CR in most sJIA patients,” Dr. Quartier and coinvestigators wrote in their article.
They added: “We believe that these results are relevant for clinical practice, particularly for designing personalized tapering strategies that can allow an adequate control of disease while minimizing the side effects of certain medications, notably glucocorticoids.”
The study was funded by Novartis in collaboration with the Pediatric Rheumatology International Trials Organization and the Pediatric Rheumatology Collaborative Study Group. Dr. Quartier was an investigator for the trial and has received research and consultancy fees from Novartis, among other pharmaceutical companies. Two of his coauthors are employees of Novartis. Dr. Ramanan has acted as an investigator in prior canakinumab trials and has received consultancy fees from Novartis and multiple other companies.
SOURCE: Quartier P et al. Arthritis Rheumatol. 2020 Aug 11. doi: 10.1002/art.41488.
A trial that tested two ways of tapering canakinumab (Ilaris) monotherapy in children with systemic juvenile idiopathic arthritis (sJIA) showed that both approaches might be feasible, but the lack of a control arm means that more data are needed before putting either into routine clinical practice.
Pierre Quartier, MD, and associates reported in Arthritis & Rheumatology. That’s with the proviso that children are taking canakinumab at the recommended dose of 4 mg/kg every 4 weeks and achieve clinical remission before any tapering is started.
The researchers found that 70%-80% of children who were in complete clinical remission (CR) maintained this for 6 months after the first dose-tapering step had been taken. However, at least one-fifth of study participants experienced a disease flare during treatment withdrawal, and only one-third were able to discontinue treatment altogether, which suggests continued treatment is needed.
“The results are a step in the right direction,” commented Athimaleipet Ramanan, MBBS, a consultant pediatric rheumatologist who was not involved in the study. They “offer the first vision of whether we can actually taper a medication” in sJIA because “until now we have not had any evidence for this,” he added.
“What we really need to know, which the study doesn’t tell you, is: Is decreasing the dose better than stopping?” said Dr. Ramanan, of the Bristol (England) Royal Hospital for Children.
Another thing that is important to know is: Does reducing the dose lead to the development of anti-drug antibodies? he said.
“There were some concerns that, when you give less of a monoclonal antibody, you might get more neutralizing anti-drug antibodies or you might make a drug more immunogenic,” he said. These data perhaps suggest that this isn’t the case because only one child on one occasion had detectable non-neutralizing anti-drug antibodies during the entire study, and that was 11 weeks after the last dose of canakinumab had been given.
Study results and design
Canakinumab is a monoclonal antibody that inhibits interleukin-1 (IL-1) that has been approved in the United States and Europe for the treatment of sJIA since 2013. Reducing a child’s exposure to canakinumab once their disease is under control is an attractive proposition given the treat-to-target approach used increasingly throughout modern rheumatologic practice. It could also help reduce the cost of what is an expensive treatment, compared with other available options for sJIA such as the interleukin-6 inhibitor tocilizumab (Actemra) or another IL-1 inhibitor anakinra (Kineret), which is not FDA-approved for use in sJIA and requires weekly injections.
“We don’t want to the disease to reappear, to flare, but we also don’t want to overuse treatments in these patients,” explained Dr. Quartier of Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris in an interview.
The study he coconducted, given the acronym B-SPECIFIC-4 Patients, was an open-label study that consisted of two parts. In part 1, 182 children were given subcutaneous canakinumab 4 mg/kg every 4 weeks. In part 2, 76 children who were in complete CR after canakinumab treatment were randomized to one of two tapering strategies. In one arm, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg given every 4 weeks before eventually discontinuing treatment, and in other arm the duration between dosing was increased by 4-week intervals, from 4 to 8 weeks, then 12 weeks, then discontinuation.
If children were taking glucocorticoids or methotrexate, the treating physicians were encouraged to stop these medications if possible, with 34%-39% and 42%-59% of children, respectively, being able to do so. The rate depended on whether children had received canakinumab before entering the study because some had been recruited from a long-term extension study while others were naive to the biologic; all had inactive disease at study entry.
This was the first study to evaluate the effectiveness of canakinumab in enabling the discontinuation of methotrexate, but the primary objective was to assess whether more than 40% of randomized patients in either discontinuation arm remained in CR for 24 weeks after the first step of discontinuation. This was achieved in 71% of children who were in the dose-reduction arm and in 84% of children in the dose-prolongation arm (P ≤ .0001 for each arm vs. 40%).
Prior exposure to canakinumab did not seem to affect the maintenance of CR, but it was also found that more children who maintained CR at their second but not their first attempt at tapering were in CR than those who were still in CR at the first step (76% and 89% in the dose-reduction and dose-prolongation arms, respectively).
Among the two dosing regimens, failure occurred in 18% of children in the dose-reduction arm at the first step, 10% at the second, and 8% at the third, whereas 2.7% of children in the dose-prolongation arm experienced regimen failure at the first step, 6.1% at the second, and 15% at the third.
No substantial difference between the two tapering approaches was observed because the study was not powered to look at this. There was also no control arm, such as a group continuing treatment while the other groups tapered, or as Dr. Ramanan had pointed out, stopping canakinumab altogether.
“As long as the treatment was continued, even at very low dosage, most patients remained in inactive disease,” Dr. Quartier said. He added, however, that only a minority of patients could stop treatment completely. Treatment should not be stopped abruptly, he advised, because this was associated with a substantial number of disease flares that needed treatment to be reinstated.
These findings suggest that “a certain level of sustained inhibition of the IL-1 pathway seems important for the maintenance of CR in most sJIA patients,” Dr. Quartier and coinvestigators wrote in their article.
They added: “We believe that these results are relevant for clinical practice, particularly for designing personalized tapering strategies that can allow an adequate control of disease while minimizing the side effects of certain medications, notably glucocorticoids.”
The study was funded by Novartis in collaboration with the Pediatric Rheumatology International Trials Organization and the Pediatric Rheumatology Collaborative Study Group. Dr. Quartier was an investigator for the trial and has received research and consultancy fees from Novartis, among other pharmaceutical companies. Two of his coauthors are employees of Novartis. Dr. Ramanan has acted as an investigator in prior canakinumab trials and has received consultancy fees from Novartis and multiple other companies.
SOURCE: Quartier P et al. Arthritis Rheumatol. 2020 Aug 11. doi: 10.1002/art.41488.
FROM ARTHRITIS & RHEUMATOLOGY
How prostate cancer treatments affect quality of life
according to a presentation at the virtual annual congress of the European Association of Urology (EAU).
Results of EUPROMS – the first patient-driven, international, prostate cancer quality of life study – showed that fatigue, insomnia, urinary incontinence, and sexual function were worse with certain types of treatments.
“Quality of life is negatively impacted by any treatment for prostate cancer other than active surveillance,” said André Deschamps, the chairman of the patient advocacy movement Europa Uomo, which conducted the study with support from Erasmus University Medical Center in Rotterdam, the Netherlands.
Active surveillance “should be promoted as the first option for treatment for those men where it can be offered safely,” Mr. Deschamps said when presenting the study at the EAU congress.
The study showed that quality of life related to urinary incontinence was lowest in patients who had undergone radical prostatectomy, and sexual function was greatly affected by radiotherapy. Radiotherapy and chemotherapy had the greatest impact on patients’ levels of fatigue, and chemotherapy was associated with “the worst possible outcomes in quality of life,” Mr. Deschamps said.
Conversely, “reported quality of life scores are the best in patients where the cancer is discovered in an early, curable stage. Hence, efforts toward early detection and awareness are essential to avoid unnecessary deterioration in quality of life,” Mr. Deschamps said.
About the survey and respondents
Between August and November 2019, 2,943 prostate cancer patients from 24 European countries completed a web-based survey made available via the Europa Uomo website. The survey took around 20 minutes to complete and used three validated quality of life questionnaires, the EORTC-QLQ-C30, the EQ-5D-5L, and EPIC-26.
“The questionnaires were available in 19 languages, so every patient could answer in their mother tongue,” Mr. Deschamps pointed out, highlighting that this was a Europe-wide survey and was estimated to account for 0.1% of the patient population in Europe.
Countries with the highest number of respondents were Norway (n = 506), Sweden (n = 386), Belgium (n = 339), Germany (n = 253), Netherlands (n = 244), France (n = 234), Denmark (n = 188), the United Kingdom (n = 187), and Poland (n = 109).
The average age of respondents was 70 years at the time of the survey and 64 years at the time of diagnosis. Most patients (82%) were living with a partner.
Two-thirds of patients had received only one treatment for prostate cancer. This was most often radical prostatectomy, external beam radiotherapy, or active surveillance. Among the 22% of patients who had received two treatments, the therapies were most often a combination of surgery and radiotherapy, androgen deprivation therapy (ADT) and radiotherapy or chemotherapy, and active surveillance and surgery.
Fatigue and insomnia
According to the EORTC-QLQ-C30 symptoms questionnaire, fatigue and insomnia were particular problems for men with prostate cancer, as denoted by scores of 25 and 24, respectively, out of a possible 100. Low scores are associated with worse fatigue and insomnia.
The researchers focused their attention on how specific cancer treatments might influence fatigue. They found that radiotherapy doubled and chemotherapy tripled the number of patients reporting fatigue, when compared with active surveillance. The incidence of fatigue was 22% (n = 304), 33% (n = 246), and 11% (n = 179), respectively.
As for insomnia, “it’s bit of a mixed view,” Mr. Deschamps said. “We believe that the progression of disease is more important for insomnia. The only thing you can say is that chemotherapy leads to an increase in reported insomnia.”
Urinary continence and sexual function
The EPIC-26 questionnaire was used to look at the health-related quality of life domains of urinary and sexual function. Sexual function was the most impacted area.
“We often hear that decline in sexual functioning is a relatively small problem for prostate cancer patients, and the effect on their quality of life should not be exaggerated,” Mr. Deschamps said in a press statement.
“We also hear that prostate cancer is typically a disease of ‘old men,’ implying that the loss of sexual function is less relevant. This survey paints a different picture,” he added.
Higher EPIC-26 scores signify better function. For urinary incontinence, the score was 100/100 for active surveillance but 65/100 when active surveillance was combined with surgery and 71/100 for surgery alone. The combination of surgery and radiotherapy carried a score of 73/100 for urinary incontinence. Radiotherapy on its own had a score of 92/100, suggesting it was the addition of the surgery that was having a significant effect. The score for radiotherapy plus ADT was 100/100, and the score for chemotherapy was 86/100.
Chemotherapy appeared to have the worst effect on sexual function, with a score of just 12/100. Radiotherapy was not far behind at 17/100, and surgery alone was 21/100. When radiotherapy and surgery were combined, the score was 15/100.
Sexual function scores were also low for all the other treatments considered – 18/100 for radiotherapy and ADT, 26/100 for active surveillance and surgery, and 57/100 for active surveillance alone.
Implications for practice
“The data collected and the analysis done provide patients and healthcare professionals with a ‘snapshot’ on the impact of treatments based on the experience of fellow patients,” Mr. Deschamps said. “We hope these results will be used to establish and disseminate realistic expectations on the effects of different treatments for prostate cancer on [quality of life].”
“This study is important because it was initiated by patients and meant for patients,” noted Monique Roobol, PhD, professor of decision-making in urology at the Erasmus University Medical Center in Rotterdam, the Netherlands, where the survey data were analyzed.
“The questionnaires were completed unrelated to a hospital visit, which means respondents had more freedom to answer and provide insight into the effect of treatment on quality of life over a longer period,” she added.
“For me, the key point is that, as health care professionals, we have underestimated the impact on the quality of life for patients treated for prostate cancer,” said Hein van Poppel, MD, PhD, of University Hospitals Leuven (Belgium), who chaired the session in which the data were presented.
Arnulf Stenzl, MD, of Tübingen (Germany) University said in a statement that the survey provided valuable information. “It uses the same questionnaires used in standard clinical settings, but it is both qualitatively and quantitatively different to the kind of study usually undertaken, so it needs to be read alongside these previous studies,” Dr. Stenzl said.
There were several strong points, he said, such as the fact that EUPROMS was the largest study of its kind and thus would “reflect the impact of treatment on a wide range of patients, with different health systems.”
As an official EAU spokesperson, Dr. Stenzl added, “We completely agree that early detection and treatment is essential if we are to avoid problems with quality of life later on. It shows that, for many men, quality of life can be poor after most prostate cancer treatment, especially in advanced disease. This message is clear, and we need to listen to the voices of these patients.”
EUPROMS was conducted by Europa Uomo in conjunction with the Erasmus University Medical Centre in Rotterdam, the Netherlands. Funding was received from Bayer, Ipsen, and Janssen. The companies had no influence over any aspect of the study. The commentators did not have conflicts of interest to disclose.
according to a presentation at the virtual annual congress of the European Association of Urology (EAU).
Results of EUPROMS – the first patient-driven, international, prostate cancer quality of life study – showed that fatigue, insomnia, urinary incontinence, and sexual function were worse with certain types of treatments.
“Quality of life is negatively impacted by any treatment for prostate cancer other than active surveillance,” said André Deschamps, the chairman of the patient advocacy movement Europa Uomo, which conducted the study with support from Erasmus University Medical Center in Rotterdam, the Netherlands.
Active surveillance “should be promoted as the first option for treatment for those men where it can be offered safely,” Mr. Deschamps said when presenting the study at the EAU congress.
The study showed that quality of life related to urinary incontinence was lowest in patients who had undergone radical prostatectomy, and sexual function was greatly affected by radiotherapy. Radiotherapy and chemotherapy had the greatest impact on patients’ levels of fatigue, and chemotherapy was associated with “the worst possible outcomes in quality of life,” Mr. Deschamps said.
Conversely, “reported quality of life scores are the best in patients where the cancer is discovered in an early, curable stage. Hence, efforts toward early detection and awareness are essential to avoid unnecessary deterioration in quality of life,” Mr. Deschamps said.
About the survey and respondents
Between August and November 2019, 2,943 prostate cancer patients from 24 European countries completed a web-based survey made available via the Europa Uomo website. The survey took around 20 minutes to complete and used three validated quality of life questionnaires, the EORTC-QLQ-C30, the EQ-5D-5L, and EPIC-26.
“The questionnaires were available in 19 languages, so every patient could answer in their mother tongue,” Mr. Deschamps pointed out, highlighting that this was a Europe-wide survey and was estimated to account for 0.1% of the patient population in Europe.
Countries with the highest number of respondents were Norway (n = 506), Sweden (n = 386), Belgium (n = 339), Germany (n = 253), Netherlands (n = 244), France (n = 234), Denmark (n = 188), the United Kingdom (n = 187), and Poland (n = 109).
The average age of respondents was 70 years at the time of the survey and 64 years at the time of diagnosis. Most patients (82%) were living with a partner.
Two-thirds of patients had received only one treatment for prostate cancer. This was most often radical prostatectomy, external beam radiotherapy, or active surveillance. Among the 22% of patients who had received two treatments, the therapies were most often a combination of surgery and radiotherapy, androgen deprivation therapy (ADT) and radiotherapy or chemotherapy, and active surveillance and surgery.
Fatigue and insomnia
According to the EORTC-QLQ-C30 symptoms questionnaire, fatigue and insomnia were particular problems for men with prostate cancer, as denoted by scores of 25 and 24, respectively, out of a possible 100. Low scores are associated with worse fatigue and insomnia.
The researchers focused their attention on how specific cancer treatments might influence fatigue. They found that radiotherapy doubled and chemotherapy tripled the number of patients reporting fatigue, when compared with active surveillance. The incidence of fatigue was 22% (n = 304), 33% (n = 246), and 11% (n = 179), respectively.
As for insomnia, “it’s bit of a mixed view,” Mr. Deschamps said. “We believe that the progression of disease is more important for insomnia. The only thing you can say is that chemotherapy leads to an increase in reported insomnia.”
Urinary continence and sexual function
The EPIC-26 questionnaire was used to look at the health-related quality of life domains of urinary and sexual function. Sexual function was the most impacted area.
“We often hear that decline in sexual functioning is a relatively small problem for prostate cancer patients, and the effect on their quality of life should not be exaggerated,” Mr. Deschamps said in a press statement.
“We also hear that prostate cancer is typically a disease of ‘old men,’ implying that the loss of sexual function is less relevant. This survey paints a different picture,” he added.
Higher EPIC-26 scores signify better function. For urinary incontinence, the score was 100/100 for active surveillance but 65/100 when active surveillance was combined with surgery and 71/100 for surgery alone. The combination of surgery and radiotherapy carried a score of 73/100 for urinary incontinence. Radiotherapy on its own had a score of 92/100, suggesting it was the addition of the surgery that was having a significant effect. The score for radiotherapy plus ADT was 100/100, and the score for chemotherapy was 86/100.
Chemotherapy appeared to have the worst effect on sexual function, with a score of just 12/100. Radiotherapy was not far behind at 17/100, and surgery alone was 21/100. When radiotherapy and surgery were combined, the score was 15/100.
Sexual function scores were also low for all the other treatments considered – 18/100 for radiotherapy and ADT, 26/100 for active surveillance and surgery, and 57/100 for active surveillance alone.
Implications for practice
“The data collected and the analysis done provide patients and healthcare professionals with a ‘snapshot’ on the impact of treatments based on the experience of fellow patients,” Mr. Deschamps said. “We hope these results will be used to establish and disseminate realistic expectations on the effects of different treatments for prostate cancer on [quality of life].”
“This study is important because it was initiated by patients and meant for patients,” noted Monique Roobol, PhD, professor of decision-making in urology at the Erasmus University Medical Center in Rotterdam, the Netherlands, where the survey data were analyzed.
“The questionnaires were completed unrelated to a hospital visit, which means respondents had more freedom to answer and provide insight into the effect of treatment on quality of life over a longer period,” she added.
“For me, the key point is that, as health care professionals, we have underestimated the impact on the quality of life for patients treated for prostate cancer,” said Hein van Poppel, MD, PhD, of University Hospitals Leuven (Belgium), who chaired the session in which the data were presented.
Arnulf Stenzl, MD, of Tübingen (Germany) University said in a statement that the survey provided valuable information. “It uses the same questionnaires used in standard clinical settings, but it is both qualitatively and quantitatively different to the kind of study usually undertaken, so it needs to be read alongside these previous studies,” Dr. Stenzl said.
There were several strong points, he said, such as the fact that EUPROMS was the largest study of its kind and thus would “reflect the impact of treatment on a wide range of patients, with different health systems.”
As an official EAU spokesperson, Dr. Stenzl added, “We completely agree that early detection and treatment is essential if we are to avoid problems with quality of life later on. It shows that, for many men, quality of life can be poor after most prostate cancer treatment, especially in advanced disease. This message is clear, and we need to listen to the voices of these patients.”
EUPROMS was conducted by Europa Uomo in conjunction with the Erasmus University Medical Centre in Rotterdam, the Netherlands. Funding was received from Bayer, Ipsen, and Janssen. The companies had no influence over any aspect of the study. The commentators did not have conflicts of interest to disclose.
according to a presentation at the virtual annual congress of the European Association of Urology (EAU).
Results of EUPROMS – the first patient-driven, international, prostate cancer quality of life study – showed that fatigue, insomnia, urinary incontinence, and sexual function were worse with certain types of treatments.
“Quality of life is negatively impacted by any treatment for prostate cancer other than active surveillance,” said André Deschamps, the chairman of the patient advocacy movement Europa Uomo, which conducted the study with support from Erasmus University Medical Center in Rotterdam, the Netherlands.
Active surveillance “should be promoted as the first option for treatment for those men where it can be offered safely,” Mr. Deschamps said when presenting the study at the EAU congress.
The study showed that quality of life related to urinary incontinence was lowest in patients who had undergone radical prostatectomy, and sexual function was greatly affected by radiotherapy. Radiotherapy and chemotherapy had the greatest impact on patients’ levels of fatigue, and chemotherapy was associated with “the worst possible outcomes in quality of life,” Mr. Deschamps said.
Conversely, “reported quality of life scores are the best in patients where the cancer is discovered in an early, curable stage. Hence, efforts toward early detection and awareness are essential to avoid unnecessary deterioration in quality of life,” Mr. Deschamps said.
About the survey and respondents
Between August and November 2019, 2,943 prostate cancer patients from 24 European countries completed a web-based survey made available via the Europa Uomo website. The survey took around 20 minutes to complete and used three validated quality of life questionnaires, the EORTC-QLQ-C30, the EQ-5D-5L, and EPIC-26.
“The questionnaires were available in 19 languages, so every patient could answer in their mother tongue,” Mr. Deschamps pointed out, highlighting that this was a Europe-wide survey and was estimated to account for 0.1% of the patient population in Europe.
Countries with the highest number of respondents were Norway (n = 506), Sweden (n = 386), Belgium (n = 339), Germany (n = 253), Netherlands (n = 244), France (n = 234), Denmark (n = 188), the United Kingdom (n = 187), and Poland (n = 109).
The average age of respondents was 70 years at the time of the survey and 64 years at the time of diagnosis. Most patients (82%) were living with a partner.
Two-thirds of patients had received only one treatment for prostate cancer. This was most often radical prostatectomy, external beam radiotherapy, or active surveillance. Among the 22% of patients who had received two treatments, the therapies were most often a combination of surgery and radiotherapy, androgen deprivation therapy (ADT) and radiotherapy or chemotherapy, and active surveillance and surgery.
Fatigue and insomnia
According to the EORTC-QLQ-C30 symptoms questionnaire, fatigue and insomnia were particular problems for men with prostate cancer, as denoted by scores of 25 and 24, respectively, out of a possible 100. Low scores are associated with worse fatigue and insomnia.
The researchers focused their attention on how specific cancer treatments might influence fatigue. They found that radiotherapy doubled and chemotherapy tripled the number of patients reporting fatigue, when compared with active surveillance. The incidence of fatigue was 22% (n = 304), 33% (n = 246), and 11% (n = 179), respectively.
As for insomnia, “it’s bit of a mixed view,” Mr. Deschamps said. “We believe that the progression of disease is more important for insomnia. The only thing you can say is that chemotherapy leads to an increase in reported insomnia.”
Urinary continence and sexual function
The EPIC-26 questionnaire was used to look at the health-related quality of life domains of urinary and sexual function. Sexual function was the most impacted area.
“We often hear that decline in sexual functioning is a relatively small problem for prostate cancer patients, and the effect on their quality of life should not be exaggerated,” Mr. Deschamps said in a press statement.
“We also hear that prostate cancer is typically a disease of ‘old men,’ implying that the loss of sexual function is less relevant. This survey paints a different picture,” he added.
Higher EPIC-26 scores signify better function. For urinary incontinence, the score was 100/100 for active surveillance but 65/100 when active surveillance was combined with surgery and 71/100 for surgery alone. The combination of surgery and radiotherapy carried a score of 73/100 for urinary incontinence. Radiotherapy on its own had a score of 92/100, suggesting it was the addition of the surgery that was having a significant effect. The score for radiotherapy plus ADT was 100/100, and the score for chemotherapy was 86/100.
Chemotherapy appeared to have the worst effect on sexual function, with a score of just 12/100. Radiotherapy was not far behind at 17/100, and surgery alone was 21/100. When radiotherapy and surgery were combined, the score was 15/100.
Sexual function scores were also low for all the other treatments considered – 18/100 for radiotherapy and ADT, 26/100 for active surveillance and surgery, and 57/100 for active surveillance alone.
Implications for practice
“The data collected and the analysis done provide patients and healthcare professionals with a ‘snapshot’ on the impact of treatments based on the experience of fellow patients,” Mr. Deschamps said. “We hope these results will be used to establish and disseminate realistic expectations on the effects of different treatments for prostate cancer on [quality of life].”
“This study is important because it was initiated by patients and meant for patients,” noted Monique Roobol, PhD, professor of decision-making in urology at the Erasmus University Medical Center in Rotterdam, the Netherlands, where the survey data were analyzed.
“The questionnaires were completed unrelated to a hospital visit, which means respondents had more freedom to answer and provide insight into the effect of treatment on quality of life over a longer period,” she added.
“For me, the key point is that, as health care professionals, we have underestimated the impact on the quality of life for patients treated for prostate cancer,” said Hein van Poppel, MD, PhD, of University Hospitals Leuven (Belgium), who chaired the session in which the data were presented.
Arnulf Stenzl, MD, of Tübingen (Germany) University said in a statement that the survey provided valuable information. “It uses the same questionnaires used in standard clinical settings, but it is both qualitatively and quantitatively different to the kind of study usually undertaken, so it needs to be read alongside these previous studies,” Dr. Stenzl said.
There were several strong points, he said, such as the fact that EUPROMS was the largest study of its kind and thus would “reflect the impact of treatment on a wide range of patients, with different health systems.”
As an official EAU spokesperson, Dr. Stenzl added, “We completely agree that early detection and treatment is essential if we are to avoid problems with quality of life later on. It shows that, for many men, quality of life can be poor after most prostate cancer treatment, especially in advanced disease. This message is clear, and we need to listen to the voices of these patients.”
EUPROMS was conducted by Europa Uomo in conjunction with the Erasmus University Medical Centre in Rotterdam, the Netherlands. Funding was received from Bayer, Ipsen, and Janssen. The companies had no influence over any aspect of the study. The commentators did not have conflicts of interest to disclose.
FROM EAU20
Better continence rate gives robotic prostatectomy the edge
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
FROM EAU20
NSAID continuation linked to less knee OA pain
in a randomized trial.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.
Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).
“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.
They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.
“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.
The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.
The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.
The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.
“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.
Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).
“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.
“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.
Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.
“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.
He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.
“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”
Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.
It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”
Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.
SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.
in a randomized trial.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.
Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).
“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.
They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.
“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.
The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.
The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.
The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.
“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.
Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).
“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.
“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.
Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.
“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.
He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.
“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”
Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.
It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”
Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.
SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.
in a randomized trial.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.
Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).
“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.
They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.
“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.
The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.
The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.
The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.
“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.
Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).
“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.
“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.
Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.
“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.
He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.
“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”
Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.
It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”
Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.
SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.
FROM JAMA INTERNAL MEDICINE
Robotic renal surgery bests open partial nephrectomy
RAPN was associated with a 61% decrease in intraoperative complications and a 71% decrease in overall complications in the IRON study.
Alessandro Larcher, MD, of San Raffaele Hospital and the Urological Research Institute in Milan, presented results from IRON during a live poster session at the virtual annual congress of the European Association of Urology.
The IRON study was performed in nine high-volume centers and involved 3,468 patients with renal cell cancer. Patients were recruited if they had a localized renal cell mass (cT1-2) with no nodal involvement or metastases. There were 2,405 patients who underwent RAPN and 1,063 who underwent OPN.
Intraoperative complications occurred in 5.7% of patients who underwent RAPN and in 9.3% of those who underwent OPN. Overall complications occurred in 33% and 18%, respectively (P < .001 for both).
“The complication profile was invariably in favor of robot-assisted surgery,” Dr. Larcher observed.
Patients who underwent RAPN had less estimated median blood loss (150 mL vs. 180 mL, P < .001) as well as lower rates of hemorrhagic complications (6.4% vs. 9%, P < .01) and urinary leakage (0.8% vs. 4.6%, P < .01).
The operative time was longer with RAPN than with OPN, at a median of 150 minutes and 120 minutes, respectively (P < .001). However, patients remained in the hospital for less time with RAPN than with OPN, at a median of 4 days and 6 days, respectively (P < .01).
RAPN was associated with fewer surgical complications than OPN according to the Clavien-Dindo system. Grade 2 or higher complications occurred in 12% and 20% of patients, respectively (P < .001). Grade 3 or higher complications occurred in 4% and 6.1%, respectively (P < .001).
“The benefit with respect to the complication risk reduction in the case of robot-assisted surgery was not affected by the tumor complexity, by the dimension of the mass, the comorbidities of the patients, or the baseline renal function,” Dr. Larcher said. “[T]he advantage after robot-assisted surgery is consistent regardless of all these features.”
Early renal function was better after OPN, but there was no significant difference between the two groups at 1 year of follow-up. The median ischemia time was 15 minutes with OPN and 16 minutes with RAPN (P < .001).
Postoperatively, the median estimated glomerular filtration rate was 78 mL/min/1.73m2 with OPN and 76 mL/min/1.73m2 with RAPN (P < .001). At 1 year, the median estimated glomerular filtration rate was 68 and 71 mL/min/1.73m2, respectively (P = .5).
Dr. Larcher noted that there was no difference between RAPN and OPN in terms of 5-year oncologic outcomes. Local recurrence occurred in 1.6% and 2.1% of patients, respectively (P = .06); systemic progression was seen in 1.8% and 4.5%, respectively (P = .5); and clinical progression was observed in 3.2% and 6.6%, respectively (P = .9).
“[IRON is] a really powerful study. It’s one of those studies that kind of has to be done,” said Ben Challacombe, MBBS, a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London who chaired the poster session during which these findings were presented.
Dr. Challacombe, who specializes in the treatment of kidney and prostatic disease using robotic surgery, noted that about 75% of procedures in the United Kingdom are now being performed with robotic assistance and queried what percentage of procedures should still be done by open surgery.
“I would turn it,” Dr. Larcher said. “What is the percentage of surgeons that should use one technique or the other?” In the IRON study, as well as other studies, surgical expertise, training, and center volumes were important.
“What the data are telling us is that those who are really confident in robotic surgeries can achieve even better outcomes, also in very complex cases,” Dr. Larcher said. “I think it’s not any longer dependent on the tumor factors. The answer to the question is only determined by human factors.”
The IRON study was supported by a grant from Intuitive. Dr. Larcher declared no conflicts of interest. Dr. Challacombe did not present any disclosures.
SOURCE: Larcher A et al. EAU20, Abstract 30. Eur Urol Open Sci 2020;19(Suppl 2):e142.
RAPN was associated with a 61% decrease in intraoperative complications and a 71% decrease in overall complications in the IRON study.
Alessandro Larcher, MD, of San Raffaele Hospital and the Urological Research Institute in Milan, presented results from IRON during a live poster session at the virtual annual congress of the European Association of Urology.
The IRON study was performed in nine high-volume centers and involved 3,468 patients with renal cell cancer. Patients were recruited if they had a localized renal cell mass (cT1-2) with no nodal involvement or metastases. There were 2,405 patients who underwent RAPN and 1,063 who underwent OPN.
Intraoperative complications occurred in 5.7% of patients who underwent RAPN and in 9.3% of those who underwent OPN. Overall complications occurred in 33% and 18%, respectively (P < .001 for both).
“The complication profile was invariably in favor of robot-assisted surgery,” Dr. Larcher observed.
Patients who underwent RAPN had less estimated median blood loss (150 mL vs. 180 mL, P < .001) as well as lower rates of hemorrhagic complications (6.4% vs. 9%, P < .01) and urinary leakage (0.8% vs. 4.6%, P < .01).
The operative time was longer with RAPN than with OPN, at a median of 150 minutes and 120 minutes, respectively (P < .001). However, patients remained in the hospital for less time with RAPN than with OPN, at a median of 4 days and 6 days, respectively (P < .01).
RAPN was associated with fewer surgical complications than OPN according to the Clavien-Dindo system. Grade 2 or higher complications occurred in 12% and 20% of patients, respectively (P < .001). Grade 3 or higher complications occurred in 4% and 6.1%, respectively (P < .001).
“The benefit with respect to the complication risk reduction in the case of robot-assisted surgery was not affected by the tumor complexity, by the dimension of the mass, the comorbidities of the patients, or the baseline renal function,” Dr. Larcher said. “[T]he advantage after robot-assisted surgery is consistent regardless of all these features.”
Early renal function was better after OPN, but there was no significant difference between the two groups at 1 year of follow-up. The median ischemia time was 15 minutes with OPN and 16 minutes with RAPN (P < .001).
Postoperatively, the median estimated glomerular filtration rate was 78 mL/min/1.73m2 with OPN and 76 mL/min/1.73m2 with RAPN (P < .001). At 1 year, the median estimated glomerular filtration rate was 68 and 71 mL/min/1.73m2, respectively (P = .5).
Dr. Larcher noted that there was no difference between RAPN and OPN in terms of 5-year oncologic outcomes. Local recurrence occurred in 1.6% and 2.1% of patients, respectively (P = .06); systemic progression was seen in 1.8% and 4.5%, respectively (P = .5); and clinical progression was observed in 3.2% and 6.6%, respectively (P = .9).
“[IRON is] a really powerful study. It’s one of those studies that kind of has to be done,” said Ben Challacombe, MBBS, a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London who chaired the poster session during which these findings were presented.
Dr. Challacombe, who specializes in the treatment of kidney and prostatic disease using robotic surgery, noted that about 75% of procedures in the United Kingdom are now being performed with robotic assistance and queried what percentage of procedures should still be done by open surgery.
“I would turn it,” Dr. Larcher said. “What is the percentage of surgeons that should use one technique or the other?” In the IRON study, as well as other studies, surgical expertise, training, and center volumes were important.
“What the data are telling us is that those who are really confident in robotic surgeries can achieve even better outcomes, also in very complex cases,” Dr. Larcher said. “I think it’s not any longer dependent on the tumor factors. The answer to the question is only determined by human factors.”
The IRON study was supported by a grant from Intuitive. Dr. Larcher declared no conflicts of interest. Dr. Challacombe did not present any disclosures.
SOURCE: Larcher A et al. EAU20, Abstract 30. Eur Urol Open Sci 2020;19(Suppl 2):e142.
RAPN was associated with a 61% decrease in intraoperative complications and a 71% decrease in overall complications in the IRON study.
Alessandro Larcher, MD, of San Raffaele Hospital and the Urological Research Institute in Milan, presented results from IRON during a live poster session at the virtual annual congress of the European Association of Urology.
The IRON study was performed in nine high-volume centers and involved 3,468 patients with renal cell cancer. Patients were recruited if they had a localized renal cell mass (cT1-2) with no nodal involvement or metastases. There were 2,405 patients who underwent RAPN and 1,063 who underwent OPN.
Intraoperative complications occurred in 5.7% of patients who underwent RAPN and in 9.3% of those who underwent OPN. Overall complications occurred in 33% and 18%, respectively (P < .001 for both).
“The complication profile was invariably in favor of robot-assisted surgery,” Dr. Larcher observed.
Patients who underwent RAPN had less estimated median blood loss (150 mL vs. 180 mL, P < .001) as well as lower rates of hemorrhagic complications (6.4% vs. 9%, P < .01) and urinary leakage (0.8% vs. 4.6%, P < .01).
The operative time was longer with RAPN than with OPN, at a median of 150 minutes and 120 minutes, respectively (P < .001). However, patients remained in the hospital for less time with RAPN than with OPN, at a median of 4 days and 6 days, respectively (P < .01).
RAPN was associated with fewer surgical complications than OPN according to the Clavien-Dindo system. Grade 2 or higher complications occurred in 12% and 20% of patients, respectively (P < .001). Grade 3 or higher complications occurred in 4% and 6.1%, respectively (P < .001).
“The benefit with respect to the complication risk reduction in the case of robot-assisted surgery was not affected by the tumor complexity, by the dimension of the mass, the comorbidities of the patients, or the baseline renal function,” Dr. Larcher said. “[T]he advantage after robot-assisted surgery is consistent regardless of all these features.”
Early renal function was better after OPN, but there was no significant difference between the two groups at 1 year of follow-up. The median ischemia time was 15 minutes with OPN and 16 minutes with RAPN (P < .001).
Postoperatively, the median estimated glomerular filtration rate was 78 mL/min/1.73m2 with OPN and 76 mL/min/1.73m2 with RAPN (P < .001). At 1 year, the median estimated glomerular filtration rate was 68 and 71 mL/min/1.73m2, respectively (P = .5).
Dr. Larcher noted that there was no difference between RAPN and OPN in terms of 5-year oncologic outcomes. Local recurrence occurred in 1.6% and 2.1% of patients, respectively (P = .06); systemic progression was seen in 1.8% and 4.5%, respectively (P = .5); and clinical progression was observed in 3.2% and 6.6%, respectively (P = .9).
“[IRON is] a really powerful study. It’s one of those studies that kind of has to be done,” said Ben Challacombe, MBBS, a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London who chaired the poster session during which these findings were presented.
Dr. Challacombe, who specializes in the treatment of kidney and prostatic disease using robotic surgery, noted that about 75% of procedures in the United Kingdom are now being performed with robotic assistance and queried what percentage of procedures should still be done by open surgery.
“I would turn it,” Dr. Larcher said. “What is the percentage of surgeons that should use one technique or the other?” In the IRON study, as well as other studies, surgical expertise, training, and center volumes were important.
“What the data are telling us is that those who are really confident in robotic surgeries can achieve even better outcomes, also in very complex cases,” Dr. Larcher said. “I think it’s not any longer dependent on the tumor factors. The answer to the question is only determined by human factors.”
The IRON study was supported by a grant from Intuitive. Dr. Larcher declared no conflicts of interest. Dr. Challacombe did not present any disclosures.
SOURCE: Larcher A et al. EAU20, Abstract 30. Eur Urol Open Sci 2020;19(Suppl 2):e142.
FROM EAU20
Bisphosphonates may have limited ‘protective’ effect against knee OA progression
New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).
In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.
While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).
“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.
“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.
Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
Study details
The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.
The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.
The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.
Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.
“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.
Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.
Results in perspective
“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.
“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.
“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.
“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.
In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.
One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.
“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.
But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.
“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.
So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.
“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”
She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”
The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.
SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).
In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.
While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).
“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.
“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.
Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
Study details
The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.
The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.
The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.
Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.
“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.
Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.
Results in perspective
“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.
“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.
“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.
“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.
In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.
One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.
“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.
But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.
“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.
So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.
“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”
She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”
The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.
SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).
In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.
While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).
“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.
“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.
Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
Study details
The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.
The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.
The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.
Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.
“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.
Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.
Results in perspective
“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.
“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.
“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.
“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.
In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.
One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.
“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.
But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.
“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.
So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.
“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”
She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”
The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.
SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
FROM THE JOURNAL OF BONE AND MINERAL RESEARCH
Intravesical BCG dosing frequency ‘critical’ in bladder cancer
The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.
More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.
At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.
“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.
“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.
Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.
Trial details
NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.
The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.
Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.
Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.
“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.
Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.
“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
Post hoc analysis
Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.
The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).
However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).
Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.
Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.
“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.
“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”
“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.
The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.
SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/
The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.
More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.
At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.
“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.
“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.
Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.
Trial details
NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.
The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.
Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.
Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.
“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.
Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.
“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
Post hoc analysis
Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.
The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).
However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).
Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.
Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.
“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.
“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”
“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.
The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.
SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/
The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.
More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.
At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.
“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.
“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.
Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.
Trial details
NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.
The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.
Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.
Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.
“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.
Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.
“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
Post hoc analysis
Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.
The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).
However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).
Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.
Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.
“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.
“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”
“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.
The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.
SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/
FROM EAU20
PSMA PET/CT may be new ‘gold standard’ for prostate cancer staging
The accuracy was 92% for PSMA PET/CT and 65% for CT and bone scintigraphy (P < .001), according to data reported at the virtual annual congress of the European Association of Urology and published in The Lancet.
In addition, PSMA PET/CT had greater effects on treatment. First-line imaging led to treatment changes in 28% of the PSMA PET/CT group and 15% of the CT/bone scan group. Second-line imaging led to treatment changes in 27% and 5% of patients, respectively.
“My strong view is that this is practice-changing data,” said study investigator Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne.
Highly relevant secondary outcomes were included in the study, Dr. Hofman said, and results were all in favor of PSMA PET/CT over conventional imaging.
PSMA PET/CT was associated with a lower rate of equivocal or uncertain findings (7% vs. 23%), and half the radiation dose was needed with PSMA PET/CT (8 mSv vs. 19 mSv). Furthermore, PSMA PET/CT was more accurate when used after CT/bone scan than when CT/bone scan was used after PSMA PET/CT (19% vs. 2%).
“PSMA PET/CT has emerged as a potential new gold standard for imaging prostate cancer,” Dr. Hofman said. The images it can produce were “striking” compared to conventional CT, he added. Pelvic and abdominal metastases that are barely visible on CT were “lighting up very brightly” on PSMA PET/CT, he said.
The study also showed that PSMA PET/CT was superior to CT/bone scans for picking up metastases throughout the body. The detection rate was 91% and 59%, respectively, for pelvic nodal metastases and 95% and 74%, respectively, for distant metastases.
Study details
ProPSMA is a multicenter, phase 3 trial directly comparing PSMA PET/CT and the standard of imaging. Of 339 men assessed for inclusion across 10 centers in Australia, 302 were randomized. They had a median age of 69 years. All patients had high-risk prostate cancer, which was defined as a prostate-specific antigen level of 20 ng/mL, Gleason Grade Group 3-5, or clinical stage T3 or higher. They were all about to undergo either surgery or radiotherapy with the intention of curing their prostate cancer.
PSMA PET/CT was performed using the gallium-68-labelled PSMA-11 tracer, but the results would likely be no different if another tracer were used, Dr. Hofman said in the discussion following his talk.
Of the three available tracers, there were minor differences, mostly in how they were excreted. However, “they’re all extremely good. I’m not sure anyone’s ever going to undertake a head-to-head study comparing them,” Dr. Hofman said.
“Whichever one you can access, at the cheapest cost, I think, is going to be the best one in your center,” he added. “That really does vary geographically, but I really don’t think one is better or worse than the other.”
Praise and criticism
The latest European guidelines acknowledge that PSMA PET/CT is more sensitive for detecting lymph node and bone metastases than the classical workup of abdominopelvic CT and bone scintigraphy, according to invited discussant Matthias Heck, PD Dr. med, of the Technical University of Munich in Germany.
“Molecular imaging using PSMA PET/CT facilitates the detection of small lymph node metastasis, with the size of a few millimeters,” Dr. Heck said.
Although he commended the ProPSMA investigators, Dr. Heck had one criticism of the study design that may have resulted in over-sensitivity of PSMA PET/CT.
“As a urologist, I want to address as a discussion point the low number of histopathologic validation in the ProPSMA study,” he said. “Pelvic lymph node sampling was performed only in 66% of patients treated with radical prostatectomy for high-risk prostate cancer. Hard criteria to define the presence of metastasis were only used in 23% of patients with metastases. Therefore, it is possible that the sensitivity was overestimated by using mainly soft criteria.”
The sensitivity of PSMA PET/CT was 85%, while that of CT/bone scan was 38%. The respective specificities were 98% and 91%.
“What I like most about this study is that, when we perform a PSMA PET/CT, you see the whole body; you don’t see only pelvic lymph nodes,” Dr. Heck said. Since it was not possible to validate distant metastasis by histopathology, he added, this imaging method could clearly help determine the best treatment.
“If we have distant metastasis in the bones or in the lymph nodes outside of the pelvis, it’s clearly unnecessary to direct this patient to undergo local treatment, and we need to think about other treatments,” Dr. Heck said. “Therefore, I think it’s a very important question that is being raised by this study, and we all need to look at the whole body of the patient and not focus only on the pelvic lymph nodes.”
The study was funded by the Prostate Cancer Foundation of Australia. Dr. Hofman said he has no relevant conflicts of interest. Dr. Heck disclosed relationships with Astellas, Janssen, Ipsen, Amgen, Bayer, Heise, Merck, Sanofi, and Takeda.
SOURCES: Hofman M et al. Lancet. March 22, doi: https://doi.org/10.1016/S0140-6736(20)30314-7.
The accuracy was 92% for PSMA PET/CT and 65% for CT and bone scintigraphy (P < .001), according to data reported at the virtual annual congress of the European Association of Urology and published in The Lancet.
In addition, PSMA PET/CT had greater effects on treatment. First-line imaging led to treatment changes in 28% of the PSMA PET/CT group and 15% of the CT/bone scan group. Second-line imaging led to treatment changes in 27% and 5% of patients, respectively.
“My strong view is that this is practice-changing data,” said study investigator Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne.
Highly relevant secondary outcomes were included in the study, Dr. Hofman said, and results were all in favor of PSMA PET/CT over conventional imaging.
PSMA PET/CT was associated with a lower rate of equivocal or uncertain findings (7% vs. 23%), and half the radiation dose was needed with PSMA PET/CT (8 mSv vs. 19 mSv). Furthermore, PSMA PET/CT was more accurate when used after CT/bone scan than when CT/bone scan was used after PSMA PET/CT (19% vs. 2%).
“PSMA PET/CT has emerged as a potential new gold standard for imaging prostate cancer,” Dr. Hofman said. The images it can produce were “striking” compared to conventional CT, he added. Pelvic and abdominal metastases that are barely visible on CT were “lighting up very brightly” on PSMA PET/CT, he said.
The study also showed that PSMA PET/CT was superior to CT/bone scans for picking up metastases throughout the body. The detection rate was 91% and 59%, respectively, for pelvic nodal metastases and 95% and 74%, respectively, for distant metastases.
Study details
ProPSMA is a multicenter, phase 3 trial directly comparing PSMA PET/CT and the standard of imaging. Of 339 men assessed for inclusion across 10 centers in Australia, 302 were randomized. They had a median age of 69 years. All patients had high-risk prostate cancer, which was defined as a prostate-specific antigen level of 20 ng/mL, Gleason Grade Group 3-5, or clinical stage T3 or higher. They were all about to undergo either surgery or radiotherapy with the intention of curing their prostate cancer.
PSMA PET/CT was performed using the gallium-68-labelled PSMA-11 tracer, but the results would likely be no different if another tracer were used, Dr. Hofman said in the discussion following his talk.
Of the three available tracers, there were minor differences, mostly in how they were excreted. However, “they’re all extremely good. I’m not sure anyone’s ever going to undertake a head-to-head study comparing them,” Dr. Hofman said.
“Whichever one you can access, at the cheapest cost, I think, is going to be the best one in your center,” he added. “That really does vary geographically, but I really don’t think one is better or worse than the other.”
Praise and criticism
The latest European guidelines acknowledge that PSMA PET/CT is more sensitive for detecting lymph node and bone metastases than the classical workup of abdominopelvic CT and bone scintigraphy, according to invited discussant Matthias Heck, PD Dr. med, of the Technical University of Munich in Germany.
“Molecular imaging using PSMA PET/CT facilitates the detection of small lymph node metastasis, with the size of a few millimeters,” Dr. Heck said.
Although he commended the ProPSMA investigators, Dr. Heck had one criticism of the study design that may have resulted in over-sensitivity of PSMA PET/CT.
“As a urologist, I want to address as a discussion point the low number of histopathologic validation in the ProPSMA study,” he said. “Pelvic lymph node sampling was performed only in 66% of patients treated with radical prostatectomy for high-risk prostate cancer. Hard criteria to define the presence of metastasis were only used in 23% of patients with metastases. Therefore, it is possible that the sensitivity was overestimated by using mainly soft criteria.”
The sensitivity of PSMA PET/CT was 85%, while that of CT/bone scan was 38%. The respective specificities were 98% and 91%.
“What I like most about this study is that, when we perform a PSMA PET/CT, you see the whole body; you don’t see only pelvic lymph nodes,” Dr. Heck said. Since it was not possible to validate distant metastasis by histopathology, he added, this imaging method could clearly help determine the best treatment.
“If we have distant metastasis in the bones or in the lymph nodes outside of the pelvis, it’s clearly unnecessary to direct this patient to undergo local treatment, and we need to think about other treatments,” Dr. Heck said. “Therefore, I think it’s a very important question that is being raised by this study, and we all need to look at the whole body of the patient and not focus only on the pelvic lymph nodes.”
The study was funded by the Prostate Cancer Foundation of Australia. Dr. Hofman said he has no relevant conflicts of interest. Dr. Heck disclosed relationships with Astellas, Janssen, Ipsen, Amgen, Bayer, Heise, Merck, Sanofi, and Takeda.
SOURCES: Hofman M et al. Lancet. March 22, doi: https://doi.org/10.1016/S0140-6736(20)30314-7.
The accuracy was 92% for PSMA PET/CT and 65% for CT and bone scintigraphy (P < .001), according to data reported at the virtual annual congress of the European Association of Urology and published in The Lancet.
In addition, PSMA PET/CT had greater effects on treatment. First-line imaging led to treatment changes in 28% of the PSMA PET/CT group and 15% of the CT/bone scan group. Second-line imaging led to treatment changes in 27% and 5% of patients, respectively.
“My strong view is that this is practice-changing data,” said study investigator Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne.
Highly relevant secondary outcomes were included in the study, Dr. Hofman said, and results were all in favor of PSMA PET/CT over conventional imaging.
PSMA PET/CT was associated with a lower rate of equivocal or uncertain findings (7% vs. 23%), and half the radiation dose was needed with PSMA PET/CT (8 mSv vs. 19 mSv). Furthermore, PSMA PET/CT was more accurate when used after CT/bone scan than when CT/bone scan was used after PSMA PET/CT (19% vs. 2%).
“PSMA PET/CT has emerged as a potential new gold standard for imaging prostate cancer,” Dr. Hofman said. The images it can produce were “striking” compared to conventional CT, he added. Pelvic and abdominal metastases that are barely visible on CT were “lighting up very brightly” on PSMA PET/CT, he said.
The study also showed that PSMA PET/CT was superior to CT/bone scans for picking up metastases throughout the body. The detection rate was 91% and 59%, respectively, for pelvic nodal metastases and 95% and 74%, respectively, for distant metastases.
Study details
ProPSMA is a multicenter, phase 3 trial directly comparing PSMA PET/CT and the standard of imaging. Of 339 men assessed for inclusion across 10 centers in Australia, 302 were randomized. They had a median age of 69 years. All patients had high-risk prostate cancer, which was defined as a prostate-specific antigen level of 20 ng/mL, Gleason Grade Group 3-5, or clinical stage T3 or higher. They were all about to undergo either surgery or radiotherapy with the intention of curing their prostate cancer.
PSMA PET/CT was performed using the gallium-68-labelled PSMA-11 tracer, but the results would likely be no different if another tracer were used, Dr. Hofman said in the discussion following his talk.
Of the three available tracers, there were minor differences, mostly in how they were excreted. However, “they’re all extremely good. I’m not sure anyone’s ever going to undertake a head-to-head study comparing them,” Dr. Hofman said.
“Whichever one you can access, at the cheapest cost, I think, is going to be the best one in your center,” he added. “That really does vary geographically, but I really don’t think one is better or worse than the other.”
Praise and criticism
The latest European guidelines acknowledge that PSMA PET/CT is more sensitive for detecting lymph node and bone metastases than the classical workup of abdominopelvic CT and bone scintigraphy, according to invited discussant Matthias Heck, PD Dr. med, of the Technical University of Munich in Germany.
“Molecular imaging using PSMA PET/CT facilitates the detection of small lymph node metastasis, with the size of a few millimeters,” Dr. Heck said.
Although he commended the ProPSMA investigators, Dr. Heck had one criticism of the study design that may have resulted in over-sensitivity of PSMA PET/CT.
“As a urologist, I want to address as a discussion point the low number of histopathologic validation in the ProPSMA study,” he said. “Pelvic lymph node sampling was performed only in 66% of patients treated with radical prostatectomy for high-risk prostate cancer. Hard criteria to define the presence of metastasis were only used in 23% of patients with metastases. Therefore, it is possible that the sensitivity was overestimated by using mainly soft criteria.”
The sensitivity of PSMA PET/CT was 85%, while that of CT/bone scan was 38%. The respective specificities were 98% and 91%.
“What I like most about this study is that, when we perform a PSMA PET/CT, you see the whole body; you don’t see only pelvic lymph nodes,” Dr. Heck said. Since it was not possible to validate distant metastasis by histopathology, he added, this imaging method could clearly help determine the best treatment.
“If we have distant metastasis in the bones or in the lymph nodes outside of the pelvis, it’s clearly unnecessary to direct this patient to undergo local treatment, and we need to think about other treatments,” Dr. Heck said. “Therefore, I think it’s a very important question that is being raised by this study, and we all need to look at the whole body of the patient and not focus only on the pelvic lymph nodes.”
The study was funded by the Prostate Cancer Foundation of Australia. Dr. Hofman said he has no relevant conflicts of interest. Dr. Heck disclosed relationships with Astellas, Janssen, Ipsen, Amgen, Bayer, Heise, Merck, Sanofi, and Takeda.
SOURCES: Hofman M et al. Lancet. March 22, doi: https://doi.org/10.1016/S0140-6736(20)30314-7.
FROM EAU20
EULAR gives pointers on intra-articular injection best practices
New EULAR recommendations for the intra-articular (IA) treatment of arthropathies aim to facilitate uniformity and quality of care for this mainstay of rheumatologic practice, according to a report on the new guidance that was presented at the annual European Congress of Rheumatology, held online this year due to COVID-19.
Until now there were no official recommendations on how best to use it in everyday practice. “This is the first time that there’s been a joint effort to develop evidence-based recommendations,” Jacqueline Usón, MD, PhD, associate professor medicine at Rey Juan Carlos University in Madrid, said in an interview. “Everything that we are saying is pretty logical, but it’s nice to see it put in recommendations based on evidence.”
IA therapy has been around for decades and is key for treating adults with a number of different conditions where synovitis, effusion, pain, or all three, are present, such as inflammatory arthritis and osteoarthritis, Dr. Usón observed during her presentation.
“Today, commonly used injectables are not only corticosteroids but also local anesthetics, hyaluronic acid, blood products, and maybe pharmaceuticals,” she said, adding that “there is a wide variation in the way intra-articular therapies are used and delivered to patients.” Health professionals also have very different views and habits depending on geographic locations and health care systems, she observed. Ironing out the variation was one of the main objectives of the recommendations.
As one of the two conveners of the EULAR task force behind the recommendations, Dr. Usón, herself a rheumatologist at University Hospital of Móstoles, pointed out that the task force brought together a range of specialties – rheumatologists, orthopedic surgeons, radiologists, nuclear medicine specialists, among others, as well as patients – to ensure that the best advice could be given.
The task force followed EULAR standard operating procedures for developing recommendations, with discussion groups, systematic literature reviews, and Delphi technique-based consensus all being employed. The literature search considered publications from 1946 up until 2019.
“We agreed on the need for more background information from health professionals and patients, so we developed two surveys: One for health professionals with 160 items, [for which] we obtained 186 responses from 26 countries; and the patient survey was made up of 44 items, translated into 10 different languages, and we obtained 200 responses,” she said.
The results of the systematic literature review and surveys were used to help form expert consensus, leading to 5 overarching principles and 11 recommendations that look at before, during, and after intra-articular therapy.
Five overarching principles
The first overarching principle recognizes the widespread use of IA therapies and that their use is specific to the disease that is being treated and “may not be interchangeable across indications,” Dr. Usón said. The second principle concerns improving patient-centered outcomes, which are “those that are relevant to the patient,” and include the benefits, harms, preferences, or implications for self-management.
“Contextual factors are important and contribute to the effect of IAT [intra-articular treatment],” she said, discussing the third principle. “These include effective communication, patient expectations, or settings [where the procedure takes place]. In addition, one should take into account that the route of delivery has in itself a placebo effect. We found that in different RCTs [randomized controlled trials], the pooled placebo effect of IA saline is moderate to large.”
The fourth principle looks at ensuring that patients and clinicians make an informed and shared decision, which is again highlighted by the first recommendation. The fifth, and last, overarching principle acknowledges that IA injections may be given by a range of health care professionals.
Advice for before, during, and after injection
Patients need to be “fully informed of the nature of the procedure, the injectable used, and potential effects – benefits and risks – [and] informed consent should be obtained and documented,” said Dr. Usón, outlining the first recommendation. “That seems common,” she said in the interview, “but when we did the survey, we realize that many patients didn’t [give consent], and the doctors didn’t even ask for it. This is why it’s a very general statement, and it’s our first recommendation. The agreement was 99%!”
The recommendations also look at the optimal settings for performing injections, such as providing a professional and private, well-lighted room, and having a resuscitation kit nearby in case patients faint. Accuracy is important, Dr. Usón said, and imaging, such as ultrasound, should be used where available to ensure accurate injection into the joint. This is an area where further research could be performed, she said, urging young rheumatologists and health professionals to consider this. “Intra-articular therapy is something that you learn and do, but you never really investigate in it,” she said.
One recommendation states that when intra-articular injections are being given to pregnant patients, the safety of injected compound must be considered, both for the mother and for the fetus. There is another recommendation on the need to perform IA injections under aseptic conditions, and another stating that patients should be offered local anesthetics, after explaining the pros and cons.
Special populations of patients are also considered, Dr. Usón said. For example, the guidance advises warning patients with diabetes of the risk of transient glycemia after IA glucocorticoids and the need to monitor their blood glucose levels carefully for a couple of days afterward.
As a rule, “IAT is not a contraindication to people with clotting or bleeding disorders, or taking antithrombotic medications,” she said, unless they are at a high risk of bleeding.
Importantly, the recommendations cover when IAT can be performed after joint replacement surgery (after at least 3 months), and the need to “avoid overuse of injected joints” while also avoiding complete immobilization for at least 24 hours afterward. The recommendations very generally cover re-injections, but not how long intervals between injections should be. When asked about interval duration after her presentation, Dr. Usón said that the usual advice is to give IA injections no more than 2-3 times a year, but it depends on the injectable.
“It wasn’t our intention to review the efficacy and the safety of the different injectables, nor to review the use of IAT in different types of joint diseases,” she said. “We do lack a lot of information, a lot of evidence in this, and I really would hope that new rheumatologists start looking into and start investigating in this topic,” she added.
Recommendations will increase awareness of good clinical practice
“IA injections are commonly administered in the rheumatology setting. This is because [IA injection] is often a useful treatment for acute flare of arthritis, particularly when it is limited to a few joints,” observed Ai Lyn Tan, MD, associate professor and honorary consultant rheumatologist at the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine.
IA injection “also relieves symptoms relatively quickly for patients; however, the response can be variable, and there are side effects associated with IA injections,” Dr. Tan added in an interview.
There is a lack of universally accepted recommendations, Dr. Tan observed, noting that while there might be some local guidelines on how to safely perform IA injections these were often not standardized and were subject to being continually updated to try to improve the experience for patients.
“It is therefore timely to learn about the new EULAR recommendations for IA injections. The advantage of this will be to increase awareness of good clinical practice for performing IA injections.”
Dr. Tan had no relevant conflicts of interest.
SOURCE: EULAR COVID-19 Recommendations. E-congress content available until Sept. 1, 2020.
New EULAR recommendations for the intra-articular (IA) treatment of arthropathies aim to facilitate uniformity and quality of care for this mainstay of rheumatologic practice, according to a report on the new guidance that was presented at the annual European Congress of Rheumatology, held online this year due to COVID-19.
Until now there were no official recommendations on how best to use it in everyday practice. “This is the first time that there’s been a joint effort to develop evidence-based recommendations,” Jacqueline Usón, MD, PhD, associate professor medicine at Rey Juan Carlos University in Madrid, said in an interview. “Everything that we are saying is pretty logical, but it’s nice to see it put in recommendations based on evidence.”
IA therapy has been around for decades and is key for treating adults with a number of different conditions where synovitis, effusion, pain, or all three, are present, such as inflammatory arthritis and osteoarthritis, Dr. Usón observed during her presentation.
“Today, commonly used injectables are not only corticosteroids but also local anesthetics, hyaluronic acid, blood products, and maybe pharmaceuticals,” she said, adding that “there is a wide variation in the way intra-articular therapies are used and delivered to patients.” Health professionals also have very different views and habits depending on geographic locations and health care systems, she observed. Ironing out the variation was one of the main objectives of the recommendations.
As one of the two conveners of the EULAR task force behind the recommendations, Dr. Usón, herself a rheumatologist at University Hospital of Móstoles, pointed out that the task force brought together a range of specialties – rheumatologists, orthopedic surgeons, radiologists, nuclear medicine specialists, among others, as well as patients – to ensure that the best advice could be given.
The task force followed EULAR standard operating procedures for developing recommendations, with discussion groups, systematic literature reviews, and Delphi technique-based consensus all being employed. The literature search considered publications from 1946 up until 2019.
“We agreed on the need for more background information from health professionals and patients, so we developed two surveys: One for health professionals with 160 items, [for which] we obtained 186 responses from 26 countries; and the patient survey was made up of 44 items, translated into 10 different languages, and we obtained 200 responses,” she said.
The results of the systematic literature review and surveys were used to help form expert consensus, leading to 5 overarching principles and 11 recommendations that look at before, during, and after intra-articular therapy.
Five overarching principles
The first overarching principle recognizes the widespread use of IA therapies and that their use is specific to the disease that is being treated and “may not be interchangeable across indications,” Dr. Usón said. The second principle concerns improving patient-centered outcomes, which are “those that are relevant to the patient,” and include the benefits, harms, preferences, or implications for self-management.
“Contextual factors are important and contribute to the effect of IAT [intra-articular treatment],” she said, discussing the third principle. “These include effective communication, patient expectations, or settings [where the procedure takes place]. In addition, one should take into account that the route of delivery has in itself a placebo effect. We found that in different RCTs [randomized controlled trials], the pooled placebo effect of IA saline is moderate to large.”
The fourth principle looks at ensuring that patients and clinicians make an informed and shared decision, which is again highlighted by the first recommendation. The fifth, and last, overarching principle acknowledges that IA injections may be given by a range of health care professionals.
Advice for before, during, and after injection
Patients need to be “fully informed of the nature of the procedure, the injectable used, and potential effects – benefits and risks – [and] informed consent should be obtained and documented,” said Dr. Usón, outlining the first recommendation. “That seems common,” she said in the interview, “but when we did the survey, we realize that many patients didn’t [give consent], and the doctors didn’t even ask for it. This is why it’s a very general statement, and it’s our first recommendation. The agreement was 99%!”
The recommendations also look at the optimal settings for performing injections, such as providing a professional and private, well-lighted room, and having a resuscitation kit nearby in case patients faint. Accuracy is important, Dr. Usón said, and imaging, such as ultrasound, should be used where available to ensure accurate injection into the joint. This is an area where further research could be performed, she said, urging young rheumatologists and health professionals to consider this. “Intra-articular therapy is something that you learn and do, but you never really investigate in it,” she said.
One recommendation states that when intra-articular injections are being given to pregnant patients, the safety of injected compound must be considered, both for the mother and for the fetus. There is another recommendation on the need to perform IA injections under aseptic conditions, and another stating that patients should be offered local anesthetics, after explaining the pros and cons.
Special populations of patients are also considered, Dr. Usón said. For example, the guidance advises warning patients with diabetes of the risk of transient glycemia after IA glucocorticoids and the need to monitor their blood glucose levels carefully for a couple of days afterward.
As a rule, “IAT is not a contraindication to people with clotting or bleeding disorders, or taking antithrombotic medications,” she said, unless they are at a high risk of bleeding.
Importantly, the recommendations cover when IAT can be performed after joint replacement surgery (after at least 3 months), and the need to “avoid overuse of injected joints” while also avoiding complete immobilization for at least 24 hours afterward. The recommendations very generally cover re-injections, but not how long intervals between injections should be. When asked about interval duration after her presentation, Dr. Usón said that the usual advice is to give IA injections no more than 2-3 times a year, but it depends on the injectable.
“It wasn’t our intention to review the efficacy and the safety of the different injectables, nor to review the use of IAT in different types of joint diseases,” she said. “We do lack a lot of information, a lot of evidence in this, and I really would hope that new rheumatologists start looking into and start investigating in this topic,” she added.
Recommendations will increase awareness of good clinical practice
“IA injections are commonly administered in the rheumatology setting. This is because [IA injection] is often a useful treatment for acute flare of arthritis, particularly when it is limited to a few joints,” observed Ai Lyn Tan, MD, associate professor and honorary consultant rheumatologist at the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine.
IA injection “also relieves symptoms relatively quickly for patients; however, the response can be variable, and there are side effects associated with IA injections,” Dr. Tan added in an interview.
There is a lack of universally accepted recommendations, Dr. Tan observed, noting that while there might be some local guidelines on how to safely perform IA injections these were often not standardized and were subject to being continually updated to try to improve the experience for patients.
“It is therefore timely to learn about the new EULAR recommendations for IA injections. The advantage of this will be to increase awareness of good clinical practice for performing IA injections.”
Dr. Tan had no relevant conflicts of interest.
SOURCE: EULAR COVID-19 Recommendations. E-congress content available until Sept. 1, 2020.
New EULAR recommendations for the intra-articular (IA) treatment of arthropathies aim to facilitate uniformity and quality of care for this mainstay of rheumatologic practice, according to a report on the new guidance that was presented at the annual European Congress of Rheumatology, held online this year due to COVID-19.
Until now there were no official recommendations on how best to use it in everyday practice. “This is the first time that there’s been a joint effort to develop evidence-based recommendations,” Jacqueline Usón, MD, PhD, associate professor medicine at Rey Juan Carlos University in Madrid, said in an interview. “Everything that we are saying is pretty logical, but it’s nice to see it put in recommendations based on evidence.”
IA therapy has been around for decades and is key for treating adults with a number of different conditions where synovitis, effusion, pain, or all three, are present, such as inflammatory arthritis and osteoarthritis, Dr. Usón observed during her presentation.
“Today, commonly used injectables are not only corticosteroids but also local anesthetics, hyaluronic acid, blood products, and maybe pharmaceuticals,” she said, adding that “there is a wide variation in the way intra-articular therapies are used and delivered to patients.” Health professionals also have very different views and habits depending on geographic locations and health care systems, she observed. Ironing out the variation was one of the main objectives of the recommendations.
As one of the two conveners of the EULAR task force behind the recommendations, Dr. Usón, herself a rheumatologist at University Hospital of Móstoles, pointed out that the task force brought together a range of specialties – rheumatologists, orthopedic surgeons, radiologists, nuclear medicine specialists, among others, as well as patients – to ensure that the best advice could be given.
The task force followed EULAR standard operating procedures for developing recommendations, with discussion groups, systematic literature reviews, and Delphi technique-based consensus all being employed. The literature search considered publications from 1946 up until 2019.
“We agreed on the need for more background information from health professionals and patients, so we developed two surveys: One for health professionals with 160 items, [for which] we obtained 186 responses from 26 countries; and the patient survey was made up of 44 items, translated into 10 different languages, and we obtained 200 responses,” she said.
The results of the systematic literature review and surveys were used to help form expert consensus, leading to 5 overarching principles and 11 recommendations that look at before, during, and after intra-articular therapy.
Five overarching principles
The first overarching principle recognizes the widespread use of IA therapies and that their use is specific to the disease that is being treated and “may not be interchangeable across indications,” Dr. Usón said. The second principle concerns improving patient-centered outcomes, which are “those that are relevant to the patient,” and include the benefits, harms, preferences, or implications for self-management.
“Contextual factors are important and contribute to the effect of IAT [intra-articular treatment],” she said, discussing the third principle. “These include effective communication, patient expectations, or settings [where the procedure takes place]. In addition, one should take into account that the route of delivery has in itself a placebo effect. We found that in different RCTs [randomized controlled trials], the pooled placebo effect of IA saline is moderate to large.”
The fourth principle looks at ensuring that patients and clinicians make an informed and shared decision, which is again highlighted by the first recommendation. The fifth, and last, overarching principle acknowledges that IA injections may be given by a range of health care professionals.
Advice for before, during, and after injection
Patients need to be “fully informed of the nature of the procedure, the injectable used, and potential effects – benefits and risks – [and] informed consent should be obtained and documented,” said Dr. Usón, outlining the first recommendation. “That seems common,” she said in the interview, “but when we did the survey, we realize that many patients didn’t [give consent], and the doctors didn’t even ask for it. This is why it’s a very general statement, and it’s our first recommendation. The agreement was 99%!”
The recommendations also look at the optimal settings for performing injections, such as providing a professional and private, well-lighted room, and having a resuscitation kit nearby in case patients faint. Accuracy is important, Dr. Usón said, and imaging, such as ultrasound, should be used where available to ensure accurate injection into the joint. This is an area where further research could be performed, she said, urging young rheumatologists and health professionals to consider this. “Intra-articular therapy is something that you learn and do, but you never really investigate in it,” she said.
One recommendation states that when intra-articular injections are being given to pregnant patients, the safety of injected compound must be considered, both for the mother and for the fetus. There is another recommendation on the need to perform IA injections under aseptic conditions, and another stating that patients should be offered local anesthetics, after explaining the pros and cons.
Special populations of patients are also considered, Dr. Usón said. For example, the guidance advises warning patients with diabetes of the risk of transient glycemia after IA glucocorticoids and the need to monitor their blood glucose levels carefully for a couple of days afterward.
As a rule, “IAT is not a contraindication to people with clotting or bleeding disorders, or taking antithrombotic medications,” she said, unless they are at a high risk of bleeding.
Importantly, the recommendations cover when IAT can be performed after joint replacement surgery (after at least 3 months), and the need to “avoid overuse of injected joints” while also avoiding complete immobilization for at least 24 hours afterward. The recommendations very generally cover re-injections, but not how long intervals between injections should be. When asked about interval duration after her presentation, Dr. Usón said that the usual advice is to give IA injections no more than 2-3 times a year, but it depends on the injectable.
“It wasn’t our intention to review the efficacy and the safety of the different injectables, nor to review the use of IAT in different types of joint diseases,” she said. “We do lack a lot of information, a lot of evidence in this, and I really would hope that new rheumatologists start looking into and start investigating in this topic,” she added.
Recommendations will increase awareness of good clinical practice
“IA injections are commonly administered in the rheumatology setting. This is because [IA injection] is often a useful treatment for acute flare of arthritis, particularly when it is limited to a few joints,” observed Ai Lyn Tan, MD, associate professor and honorary consultant rheumatologist at the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine.
IA injection “also relieves symptoms relatively quickly for patients; however, the response can be variable, and there are side effects associated with IA injections,” Dr. Tan added in an interview.
There is a lack of universally accepted recommendations, Dr. Tan observed, noting that while there might be some local guidelines on how to safely perform IA injections these were often not standardized and were subject to being continually updated to try to improve the experience for patients.
“It is therefore timely to learn about the new EULAR recommendations for IA injections. The advantage of this will be to increase awareness of good clinical practice for performing IA injections.”
Dr. Tan had no relevant conflicts of interest.
SOURCE: EULAR COVID-19 Recommendations. E-congress content available until Sept. 1, 2020.
FROM THE EULAR 2020 E-CONGRESS
Antinuclear antibody test interpretation guidance gets updated
New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.
ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.
“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.
There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.
In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.
The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.
Which test methodology to use?
There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?
The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”
Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.
“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”
The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.
“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.
In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”
Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.
New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.
ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.
“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.
There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.
In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.
The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.
Which test methodology to use?
There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?
The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”
Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.
“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”
The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.
“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.
In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”
Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.
New recommendations from the European League Against Rheumatism on interpreting the results of antinuclear antibody (ANA) testing advised taking the test methodology into account because of differences in performance.
ANA results vary not only by the test being used but also by the underlying disease they are being used to assess, warned Pier Luigi Meroni, MD, director of the Immunorheumatology Research Laboratory at the IRCCS Istituto Auxologico Italiano in Milan.
“Antinuclear antibody testing is a known diagnostic tool. But the recent advances in methodologies strongly suggests that we have to update our knowledge for a better interpretation of the results,” Dr. Meroni said in his presentation at the annual European Congress of Rheumatology, held online this year due to COVID-19.
There is “no doubt that ANA testing is useful,” he continued, adding that ANA is used as a primary screening tool in many rheumatic diseases, notably systemic lupus erythematosus (SLE), primary Sjögren’s syndrome, and systemic sclerosis. It’s also recently been suggested as an important entry criterion for the classification of SLE.
In fact, the 2019 SLE classification criteria – developed by EULAR in collaboration with the American College of Rheumatology – state that “testing by immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance is highly recommended,” Dr. Meroni said.
The ideas underpinning that recommendation was that “ANA expression is invariable in SLE, and that ANA-negative lupus is quite rare,” he explained. Also, as SLE expression persists over time, ANA testing could be used for classification at any point in the disease course. These assumptions have been borne out in several studies, with very small percentages of patients (6% or less) having ANA-negative lupus, and more than 80% having a positive HEp-2 test over time, even with immunosuppressive treatment.
Which test methodology to use?
There are several methods that can be used to detect ANA, including the preferred HEp-2 indirect fluorescence assay (IFA), several solid-phase assays (SpA), and line- or dot-blot immunoassays. The issue is which assay should be used in which disease?
The performance of a particular assay can depend on the disease in which they are used. For instance, while the HEp-2 IFA and SpA are equivalent in SLE and in other connective tissue diseases, “this is not the case for other autoimmune diseases in which basically we don’t know exactly all the autoantigens,” Dr. Meroni explained. “Most of the autoantigens are undefined. They cannot be found in solid-phase kits, and we have to use the IFA for detecting all these autoantibodies.”
Importantly, neither the IFA nor the SpA is superior to the other. “We just say that one technique can detect relevant antibodies that are not detectable by the other one, and maybe the combination of the two techniques can be the right strategy to get the highest sensitivity,” Dr. Meroni said.
“Clinicians should be aware of the type of assay used for ANA detection,” he said, “because there are strong differences in the performance, for example between IFA and SpA, and such differences can have important clinical and relevant consequences.”
The test selected will depend on if the aim is to exclude or confirm a disease, and the optimal strategy will depend on pretest probability. For instance, IFA is more sensitive than SpA for SLE and scleroderma, whereas IFA is less sensitive than SpA for Sjögren’s. For SLE, it is suggested to use both the IFA and SpA. A combination of both tests is also considered optimal for scleroderma. SpA testing offers the best sensitivity for Sjögren’s.
“The story is a little bit more complicated for inflammatory myopathies in which we don’t have assays able to detect all the autoantibodies,” Dr. Meroni said. In that situation, several different techniques have to be used to check if the SpA results fit with the IFA pattern.
In 2019, the ACR released its own position statement on ANA testing, highlighting that it supported the use of the HEp-2 IFA assay as the preferred option for ANA testing and that labs should specify the methods being used to test for ANA when reporting their results. The ACR position statement also noted that “ordering health care professionals should select specific ANA subserologies based on a patient’s signs and symptoms and when there is a high pretest suspicion for a specific condition.”
Dr. Meroni disclosed serving as a consultant to Inova Diagnostics, Thermo Fisher Scientific, Pfizer, AbbVie, Merck Sharp & Dohme, and UCB.
FROM THE EULAR 2020 E-CONGRESS