Rheumatoid Arthritis

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

jevans@mdedge.com

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

jevans@mdedge.com

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

jevans@mdedge.com

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.

ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.

Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
 

A pricey comparator

In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.

The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.

“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
 

Weighing efficacy and cost

Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.

CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).

Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”

After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:

• Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
• Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
• Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.

jremaly@mdedge.com

Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.

ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.

Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
 

A pricey comparator

In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.

The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.

“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
 

Weighing efficacy and cost

Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.

CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).

Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”

After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:

• Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
• Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
• Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.

jremaly@mdedge.com

Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.

ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.

Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
 

A pricey comparator

In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.

The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.

“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
 

Weighing efficacy and cost

Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.

CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).

Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”

After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:

• Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
• Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
• Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.

jremaly@mdedge.com

Women whose rheumatoid arthritis is carefully managed before and during pregnancy have a significantly lower risk of adverse pregnancy outcomes, including miscarriage or perinatal death, new research suggests.

zoranm/Getty Images

A study published in Arthritis Care & Research presents the outcomes of a retrospective, observational study examining health care data from 443 first pregnancies in women with RA and 6,097 women without the disease.

First author Alessandra Bortoluzzi, MD, PhD, from the Rheumatology Unit at the University of Ferrara (Italy) and coauthors looked at seven diagnostic, therapeutic, and follow-up health care quality indicators during the prepregnancy and perinatal period. They included having at least one blood test in the 18 months before conception and during pregnancy, preconception musculoskeletal imaging, no exposure or wash-out from teratogenic drugs, and no exposure to biologic drugs between conception and delivery or end of pregnancy.

An ideal clinical pathway included at least one element from each of the diagnostic, therapeutic, and prenatal follow-up quality indicators.

Overall, women with RA had a significantly higher rate of thyroid diseases, adverse pregnancy outcomes, and miscarriage or perinatal death when compared with controls. However, those who followed the ideal clinical pathway for management of their disease during pregnancy had a 40% lower odds of adverse pregnancy outcomes (odds ratio, 0.60; 95% confidence interval, 0.39-0.94) and a 60% lower odds of miscarriage or perinatal death (OR, 0.40; 95% CI, 0.24-0.69) in comparison with women with RA who were not managed to the same standard. The researchers adjusted both comparisons for age, Charlson comorbidity index, and thyroid diseases.

Women with RA who met diagnostic, therapeutic, and prenatal follow-up quality indicators showed no significant differences from the general population in terms of the risk of adverse pregnancy outcomes, miscarriage, or perinatal death after adjusting for hypertension in addition to the same variables as before.

When researchers looked at some of the individual health care quality indicators, they found that testing for antiphospholipid (aPL) antibodies within 18 months of conception or pregnancy was associated with a 44% lower rate of adverse pregnancy outcomes. Similarly, antinuclear antibody or anti–extractable nuclear antigen antibody testing was associated with 36% lower odds of adverse pregnancy outcomes.

Dr. Bortoluzzi and her coauthors wrote that their findings pointed to the value of testing for aPL antibodies in women with RA who wish to get pregnant.

“In fact, despite the absence of formal recommendation or validated health care quality indicators focused on stratification of preconceptional obstetric risk in patients with RA, we started from the basic and universally accepted assumption that aPL antibodies are pathogenic autoantibodies and therefore recognized risk factors for adverse pregnancy outcome,” they wrote.

Women with RA who had either no exposure to methotrexate or leflunomide or who had a washout period from 6 months prior to conception had 72% lower odds of adverse pregnancy outcomes.

The authors also looked at the effects of drugs such as aspirin, glucocorticoids, and low-molecular-weight heparin that are used during pregnancy. They found that the relative risk of adverse pregnancy outcomes was 40% higher in women with RA who were taking glucocorticoids, compared with those with the disease but not taking that type of medication. However, low-molecular-weight heparin use was associated with an 80% lower relative risk of miscarriage or perinatal death in comparison with those not taking it. Researchers saw no significant effects of aspirin or conventional synthetic disease-modifying antirheumatic drugs on either adverse pregnancy outcomes or the risk of miscarriage or perinatal death.

“This reinforces the importance of adjustment of therapy for RA before conception and throughout pregnancy, because medication use could affect pregnancy course not only influencing maternal disease activity but also the gestational outcome,” the authors wrote. “Although this is a study conducted on administrative data, we can hypothesize that exposure to therapy represents a marker of high RA disease activity and severity. In our setting, it is possible that, the more active the disease, the greater the probability of being included in the ideal clinical pathway, but in any case, this resulted in a lower odds ratio of adverse pregnancy outcome and miscarriage/perinatal death.”

The study was supported by the Italian Society for Rheumatology. No conflicts of interest were declared.

SOURCE: Bortoluzzi A et al. Arthritis Care Res. 2020 Jan 8. doi: 10.1002/ACR.24116.

Women whose rheumatoid arthritis is carefully managed before and during pregnancy have a significantly lower risk of adverse pregnancy outcomes, including miscarriage or perinatal death, new research suggests.

zoranm/Getty Images

A study published in Arthritis Care & Research presents the outcomes of a retrospective, observational study examining health care data from 443 first pregnancies in women with RA and 6,097 women without the disease.

First author Alessandra Bortoluzzi, MD, PhD, from the Rheumatology Unit at the University of Ferrara (Italy) and coauthors looked at seven diagnostic, therapeutic, and follow-up health care quality indicators during the prepregnancy and perinatal period. They included having at least one blood test in the 18 months before conception and during pregnancy, preconception musculoskeletal imaging, no exposure or wash-out from teratogenic drugs, and no exposure to biologic drugs between conception and delivery or end of pregnancy.

An ideal clinical pathway included at least one element from each of the diagnostic, therapeutic, and prenatal follow-up quality indicators.

Overall, women with RA had a significantly higher rate of thyroid diseases, adverse pregnancy outcomes, and miscarriage or perinatal death when compared with controls. However, those who followed the ideal clinical pathway for management of their disease during pregnancy had a 40% lower odds of adverse pregnancy outcomes (odds ratio, 0.60; 95% confidence interval, 0.39-0.94) and a 60% lower odds of miscarriage or perinatal death (OR, 0.40; 95% CI, 0.24-0.69) in comparison with women with RA who were not managed to the same standard. The researchers adjusted both comparisons for age, Charlson comorbidity index, and thyroid diseases.

Women with RA who met diagnostic, therapeutic, and prenatal follow-up quality indicators showed no significant differences from the general population in terms of the risk of adverse pregnancy outcomes, miscarriage, or perinatal death after adjusting for hypertension in addition to the same variables as before.

When researchers looked at some of the individual health care quality indicators, they found that testing for antiphospholipid (aPL) antibodies within 18 months of conception or pregnancy was associated with a 44% lower rate of adverse pregnancy outcomes. Similarly, antinuclear antibody or anti–extractable nuclear antigen antibody testing was associated with 36% lower odds of adverse pregnancy outcomes.

Dr. Bortoluzzi and her coauthors wrote that their findings pointed to the value of testing for aPL antibodies in women with RA who wish to get pregnant.

“In fact, despite the absence of formal recommendation or validated health care quality indicators focused on stratification of preconceptional obstetric risk in patients with RA, we started from the basic and universally accepted assumption that aPL antibodies are pathogenic autoantibodies and therefore recognized risk factors for adverse pregnancy outcome,” they wrote.

Women with RA who had either no exposure to methotrexate or leflunomide or who had a washout period from 6 months prior to conception had 72% lower odds of adverse pregnancy outcomes.

The authors also looked at the effects of drugs such as aspirin, glucocorticoids, and low-molecular-weight heparin that are used during pregnancy. They found that the relative risk of adverse pregnancy outcomes was 40% higher in women with RA who were taking glucocorticoids, compared with those with the disease but not taking that type of medication. However, low-molecular-weight heparin use was associated with an 80% lower relative risk of miscarriage or perinatal death in comparison with those not taking it. Researchers saw no significant effects of aspirin or conventional synthetic disease-modifying antirheumatic drugs on either adverse pregnancy outcomes or the risk of miscarriage or perinatal death.

“This reinforces the importance of adjustment of therapy for RA before conception and throughout pregnancy, because medication use could affect pregnancy course not only influencing maternal disease activity but also the gestational outcome,” the authors wrote. “Although this is a study conducted on administrative data, we can hypothesize that exposure to therapy represents a marker of high RA disease activity and severity. In our setting, it is possible that, the more active the disease, the greater the probability of being included in the ideal clinical pathway, but in any case, this resulted in a lower odds ratio of adverse pregnancy outcome and miscarriage/perinatal death.”

The study was supported by the Italian Society for Rheumatology. No conflicts of interest were declared.

SOURCE: Bortoluzzi A et al. Arthritis Care Res. 2020 Jan 8. doi: 10.1002/ACR.24116.

Women whose rheumatoid arthritis is carefully managed before and during pregnancy have a significantly lower risk of adverse pregnancy outcomes, including miscarriage or perinatal death, new research suggests.

zoranm/Getty Images

A study published in Arthritis Care & Research presents the outcomes of a retrospective, observational study examining health care data from 443 first pregnancies in women with RA and 6,097 women without the disease.

First author Alessandra Bortoluzzi, MD, PhD, from the Rheumatology Unit at the University of Ferrara (Italy) and coauthors looked at seven diagnostic, therapeutic, and follow-up health care quality indicators during the prepregnancy and perinatal period. They included having at least one blood test in the 18 months before conception and during pregnancy, preconception musculoskeletal imaging, no exposure or wash-out from teratogenic drugs, and no exposure to biologic drugs between conception and delivery or end of pregnancy.

An ideal clinical pathway included at least one element from each of the diagnostic, therapeutic, and prenatal follow-up quality indicators.

Overall, women with RA had a significantly higher rate of thyroid diseases, adverse pregnancy outcomes, and miscarriage or perinatal death when compared with controls. However, those who followed the ideal clinical pathway for management of their disease during pregnancy had a 40% lower odds of adverse pregnancy outcomes (odds ratio, 0.60; 95% confidence interval, 0.39-0.94) and a 60% lower odds of miscarriage or perinatal death (OR, 0.40; 95% CI, 0.24-0.69) in comparison with women with RA who were not managed to the same standard. The researchers adjusted both comparisons for age, Charlson comorbidity index, and thyroid diseases.

Women with RA who met diagnostic, therapeutic, and prenatal follow-up quality indicators showed no significant differences from the general population in terms of the risk of adverse pregnancy outcomes, miscarriage, or perinatal death after adjusting for hypertension in addition to the same variables as before.

When researchers looked at some of the individual health care quality indicators, they found that testing for antiphospholipid (aPL) antibodies within 18 months of conception or pregnancy was associated with a 44% lower rate of adverse pregnancy outcomes. Similarly, antinuclear antibody or anti–extractable nuclear antigen antibody testing was associated with 36% lower odds of adverse pregnancy outcomes.

Dr. Bortoluzzi and her coauthors wrote that their findings pointed to the value of testing for aPL antibodies in women with RA who wish to get pregnant.

“In fact, despite the absence of formal recommendation or validated health care quality indicators focused on stratification of preconceptional obstetric risk in patients with RA, we started from the basic and universally accepted assumption that aPL antibodies are pathogenic autoantibodies and therefore recognized risk factors for adverse pregnancy outcome,” they wrote.

Women with RA who had either no exposure to methotrexate or leflunomide or who had a washout period from 6 months prior to conception had 72% lower odds of adverse pregnancy outcomes.

The authors also looked at the effects of drugs such as aspirin, glucocorticoids, and low-molecular-weight heparin that are used during pregnancy. They found that the relative risk of adverse pregnancy outcomes was 40% higher in women with RA who were taking glucocorticoids, compared with those with the disease but not taking that type of medication. However, low-molecular-weight heparin use was associated with an 80% lower relative risk of miscarriage or perinatal death in comparison with those not taking it. Researchers saw no significant effects of aspirin or conventional synthetic disease-modifying antirheumatic drugs on either adverse pregnancy outcomes or the risk of miscarriage or perinatal death.

“This reinforces the importance of adjustment of therapy for RA before conception and throughout pregnancy, because medication use could affect pregnancy course not only influencing maternal disease activity but also the gestational outcome,” the authors wrote. “Although this is a study conducted on administrative data, we can hypothesize that exposure to therapy represents a marker of high RA disease activity and severity. In our setting, it is possible that, the more active the disease, the greater the probability of being included in the ideal clinical pathway, but in any case, this resulted in a lower odds ratio of adverse pregnancy outcome and miscarriage/perinatal death.”

The study was supported by the Italian Society for Rheumatology. No conflicts of interest were declared.

SOURCE: Bortoluzzi A et al. Arthritis Care Res. 2020 Jan 8. doi: 10.1002/ACR.24116.

LAS VEGAS – Nearly a quarter of American adults are on a prescription drug that often produces obesity as a side effect, and use of such obesogenic drugs was significantly higher among patients who already are obese, based on national U.S. data collected during 2013-2016.

Mitchel L. Zoler/MDedge News

The Endocrine Society, the STOP Obesity Alliance, and other medical societies have recommended that clinicians try to minimize use of obesogenic drugs and focus on prescribing agents that are weight neutral or that trigger weight loss when those options are available and appropriate, and the new findings add further evidence that clinicians need to be more mindful of this issue, Craig M. Hales, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Among the American adults interviewed for the survey, 40% of those on at least one prescription medication were on at least one drug that is considered obesogenic, said Dr. Hales, a medical epidemiologist at the Centers for Disease Control and Prevention in Hyattsville, Md.

According to practice guidelines published by the Endocrine Society, all drugs in the classes of glucocorticoids, beta-blockers, and antihistamines are obesogenic, as well as selected agents in the classes of antidepressant drugs, antipsychotics, antidepressants, antidiabetics, and contraceptives that are progestin only, said Dr. Hales (J Clin Endocrinol Metab. 2015 Feb;100[2]:342-62).

The data he reported came from the National Health and Nutrition Examination Survey (NHANES) run by the CDC during 2013-2016 that included 11,055 adults who were at least 20 years old. The findings showed that 23% of those adults had taken at least one drug that was considered obesogenic during the 30 days preceding the survey date. By comparison, 35% of the same adults had taken any type of prescription drug during the previous 30 days. That meant that overall, 40% of surveyed adults who had recently used any prescription medication had taken an obesogenic drug.

The 23% prevalence of recent obesogenic drug use was fairly stable at that level during several preceding NHANES surveys going back to 2001, suggesting that the increasing use of obesogenic drugs during the period since 2001 was not a factor in the recent increased prevalence of obesity among U.S. residents, added Dr. Hales.

The 2013-2016 analysis also showed a strong link between obesogenic drug use and increasing obesity severity. Among survey participants with a body mass index (BMI) in the normal range (18.5-24 kg/m²), 16% had recent use of an obesogenic drug. This prevalence increased to 22% among those who were overweight (BMI, 25-29 kg/m²), 29% among those with class 1 or 2 obesity (BMI, 30-39 kg/m²), and 33% among those with class 3 obesity (BMI, 40 kg/m² or greater).

In contrast, recent use of prescription medications that do not contribute to obesity showed no significant relationship with BMI, with rates that ranged from 34% among those with a normal BMI, to 37% among those with class 3 obesity.

As an example of this relationship for a specific obesogenic drug class, the prevalence of beta-blocker use was about 7% among people with a normal BMI, about 10% among those who were overweight, about 14% among people with class 1 or 2 obesity, and about 17% among people with class 3 obesity, a statistically significant link suggesting that the relationship between use of obesogenic drugs and obesity is “bidirectional,” Dr. Hales said, in that increasing obesogenic drug use likely contributes to obesity, while simultaneously, the more obese people become, the more likely they are to take additional prescription drugs, particularly those that are obesogenic.

NHANES is run by the CDC and receives no commercial funding. The authors reported no conflicts of interest.

mzoler@mdedge.com

SOURCE: Hales CM et al. Obesity Week 2019, Abstract T-OR-2037.

LAS VEGAS – Nearly a quarter of American adults are on a prescription drug that often produces obesity as a side effect, and use of such obesogenic drugs was significantly higher among patients who already are obese, based on national U.S. data collected during 2013-2016.

Mitchel L. Zoler/MDedge News

The Endocrine Society, the STOP Obesity Alliance, and other medical societies have recommended that clinicians try to minimize use of obesogenic drugs and focus on prescribing agents that are weight neutral or that trigger weight loss when those options are available and appropriate, and the new findings add further evidence that clinicians need to be more mindful of this issue, Craig M. Hales, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Among the American adults interviewed for the survey, 40% of those on at least one prescription medication were on at least one drug that is considered obesogenic, said Dr. Hales, a medical epidemiologist at the Centers for Disease Control and Prevention in Hyattsville, Md.

According to practice guidelines published by the Endocrine Society, all drugs in the classes of glucocorticoids, beta-blockers, and antihistamines are obesogenic, as well as selected agents in the classes of antidepressant drugs, antipsychotics, antidepressants, antidiabetics, and contraceptives that are progestin only, said Dr. Hales (J Clin Endocrinol Metab. 2015 Feb;100[2]:342-62).

The data he reported came from the National Health and Nutrition Examination Survey (NHANES) run by the CDC during 2013-2016 that included 11,055 adults who were at least 20 years old. The findings showed that 23% of those adults had taken at least one drug that was considered obesogenic during the 30 days preceding the survey date. By comparison, 35% of the same adults had taken any type of prescription drug during the previous 30 days. That meant that overall, 40% of surveyed adults who had recently used any prescription medication had taken an obesogenic drug.

The 23% prevalence of recent obesogenic drug use was fairly stable at that level during several preceding NHANES surveys going back to 2001, suggesting that the increasing use of obesogenic drugs during the period since 2001 was not a factor in the recent increased prevalence of obesity among U.S. residents, added Dr. Hales.

The 2013-2016 analysis also showed a strong link between obesogenic drug use and increasing obesity severity. Among survey participants with a body mass index (BMI) in the normal range (18.5-24 kg/m²), 16% had recent use of an obesogenic drug. This prevalence increased to 22% among those who were overweight (BMI, 25-29 kg/m²), 29% among those with class 1 or 2 obesity (BMI, 30-39 kg/m²), and 33% among those with class 3 obesity (BMI, 40 kg/m² or greater).

In contrast, recent use of prescription medications that do not contribute to obesity showed no significant relationship with BMI, with rates that ranged from 34% among those with a normal BMI, to 37% among those with class 3 obesity.

As an example of this relationship for a specific obesogenic drug class, the prevalence of beta-blocker use was about 7% among people with a normal BMI, about 10% among those who were overweight, about 14% among people with class 1 or 2 obesity, and about 17% among people with class 3 obesity, a statistically significant link suggesting that the relationship between use of obesogenic drugs and obesity is “bidirectional,” Dr. Hales said, in that increasing obesogenic drug use likely contributes to obesity, while simultaneously, the more obese people become, the more likely they are to take additional prescription drugs, particularly those that are obesogenic.

NHANES is run by the CDC and receives no commercial funding. The authors reported no conflicts of interest.

mzoler@mdedge.com

SOURCE: Hales CM et al. Obesity Week 2019, Abstract T-OR-2037.

LAS VEGAS – Nearly a quarter of American adults are on a prescription drug that often produces obesity as a side effect, and use of such obesogenic drugs was significantly higher among patients who already are obese, based on national U.S. data collected during 2013-2016.

Mitchel L. Zoler/MDedge News

The Endocrine Society, the STOP Obesity Alliance, and other medical societies have recommended that clinicians try to minimize use of obesogenic drugs and focus on prescribing agents that are weight neutral or that trigger weight loss when those options are available and appropriate, and the new findings add further evidence that clinicians need to be more mindful of this issue, Craig M. Hales, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Among the American adults interviewed for the survey, 40% of those on at least one prescription medication were on at least one drug that is considered obesogenic, said Dr. Hales, a medical epidemiologist at the Centers for Disease Control and Prevention in Hyattsville, Md.

According to practice guidelines published by the Endocrine Society, all drugs in the classes of glucocorticoids, beta-blockers, and antihistamines are obesogenic, as well as selected agents in the classes of antidepressant drugs, antipsychotics, antidepressants, antidiabetics, and contraceptives that are progestin only, said Dr. Hales (J Clin Endocrinol Metab. 2015 Feb;100[2]:342-62).

The data he reported came from the National Health and Nutrition Examination Survey (NHANES) run by the CDC during 2013-2016 that included 11,055 adults who were at least 20 years old. The findings showed that 23% of those adults had taken at least one drug that was considered obesogenic during the 30 days preceding the survey date. By comparison, 35% of the same adults had taken any type of prescription drug during the previous 30 days. That meant that overall, 40% of surveyed adults who had recently used any prescription medication had taken an obesogenic drug.

The 23% prevalence of recent obesogenic drug use was fairly stable at that level during several preceding NHANES surveys going back to 2001, suggesting that the increasing use of obesogenic drugs during the period since 2001 was not a factor in the recent increased prevalence of obesity among U.S. residents, added Dr. Hales.

The 2013-2016 analysis also showed a strong link between obesogenic drug use and increasing obesity severity. Among survey participants with a body mass index (BMI) in the normal range (18.5-24 kg/m²), 16% had recent use of an obesogenic drug. This prevalence increased to 22% among those who were overweight (BMI, 25-29 kg/m²), 29% among those with class 1 or 2 obesity (BMI, 30-39 kg/m²), and 33% among those with class 3 obesity (BMI, 40 kg/m² or greater).

In contrast, recent use of prescription medications that do not contribute to obesity showed no significant relationship with BMI, with rates that ranged from 34% among those with a normal BMI, to 37% among those with class 3 obesity.

As an example of this relationship for a specific obesogenic drug class, the prevalence of beta-blocker use was about 7% among people with a normal BMI, about 10% among those who were overweight, about 14% among people with class 1 or 2 obesity, and about 17% among people with class 3 obesity, a statistically significant link suggesting that the relationship between use of obesogenic drugs and obesity is “bidirectional,” Dr. Hales said, in that increasing obesogenic drug use likely contributes to obesity, while simultaneously, the more obese people become, the more likely they are to take additional prescription drugs, particularly those that are obesogenic.

NHANES is run by the CDC and receives no commercial funding. The authors reported no conflicts of interest.

mzoler@mdedge.com

SOURCE: Hales CM et al. Obesity Week 2019, Abstract T-OR-2037.

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

The length of time a patient with rheumatoid arthritis takes a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate before switching to a biologic DMARD varies widely, and the variation is largely related to differences in prescriber preference, researchers say.

They found that 65% of the variation was attributed to differences between prescribers rather than patient variables. Another 4.6% was associated with regional differences in biologic DMARD use, and 30.4% of the variation was unexplained.

“Although disparities in access to biologic DMARDs increased in this study, the overall prescription percentage decreased relative to the population of active medication users with RA. This suggests that despite rheumatologists prescribing fewer biologic DMARDs on average per patient per unit of time, variations in the prescription of biologic DMARDs continue to grow,” the researchers explain.

The clinical implications of these differences in prescriber preferences are unclear, but the findings “show that between-prescriber differences exist in health care delivery for patients with RA, despite identical health insurance coverage,” they continue.

Mark Tatangelo of the University of Toronto and colleagues published their findings online Dec. 6, 2019, in JAMA Network Open.

They examined factors associated with the length of time from first csDMARD to receipt of first biologic in a retrospective cohort study using administrative data for 17,672 patients with RA and identical single-payer health insurance coverage in Ontario.

Patients were aged 67 years or older, had incident RA, and had received at least one csDMARD. The observation window was 2002 to 2015. During the study 719 patients (4.1%) received a first biologic DMARD. The primary outcome was time from first csDMARD to receipt of first biologic DMARD.

In an invited commentary, Natalie McCormick, PhD, from the clinical epidemiology program at Massachusetts General Hospital in Boston, writes: “A distinctive feature of the report by Tatangelo et al. was the emphasis on longer time to initiation of biologic therapy as an ideal outcome.”

Factors associated with a quicker move from csDMARDs to biologic DMARDs included younger age, female sex, living in an urban area close to prescribers, and longer disease duration. The shift to biologic DMARDs was also earlier for prescribers who were more recent graduates, in urban areas, and in areas with a greater supply of rheumatologists.

Dr. McCormick suggests that the association between earlier biologic DMARD use and higher concentration of rheumatologists might indicate that “peer effects” influence prescribing decisions.

Factors associated with a more prolonged time on csDMARDs before beginning a biologic DMARD included older age, male sex, and distance to the nearest rheumatologist.

Immigrants born outside of Canada were 41% less likely to have begun biologic DMARDs. “While its mechanism and implications warrant further investigation, this finding is novel and compelling, and it could become increasingly important,” Dr. McCormick writes.

The variation in highest biologic DMARD use, compared with lowest use among the regions in Ontario rose from 1.8% in 2002 to 8.7% in 2015. In models adjusted for age, sex, calendar year, and all patient and physician covariates, regional differences accounted for 4.6% of the variation in biologic DMARD prescription.

“A 4.6% difference in time to receipt of biologic DMARDs between regions should be considered problematic in the absence of other explanatory factors,” the authors write. “For example, every 1% increase in biologic prescriptions among a population of 72,000 funded patients with RA costs approximately CaD $10.8 million (U.S. $8.25 million) per year (assuming 10% biologics penetration and CaD $15,000 annually per biologic DMARD prescription [U.S. $11,460]).”

They explain that reducing the highest spending region in Ontario to the average spend would save approximately CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million) per year, whereas increasing biologic use in the underserved regions to the population average would cost about CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million).

Dr. McCormick writes that both undertreatment and overtreatment need more study and adds that the age gradient identified in this study “may reflect an ongoing bias against prescribing biologic DMARDs to elderly patients, despite a lack of evidence that older patients have a higher risk of infections or other adverse events.”

Dr. McCormick and the researchers emphasize that the decision to begin biologic DMARDs should not be taken lightly. “[S]mall changes in time to first biologic DMARD have major clinical and economic impacts. From a clinical perspective, the prescription of a biologic DMARD represents a transition to a more complex care plan, with less data to support the next prescription choice after the first biologic DMARD,” the authors warn.

This study was funded by grants from the Canadian Institute of Health Research, the Arthritis Society, the Ontario Drug Policy Research and Effectiveness Network, and the Canadian Institute of Health Research Drug Safety and Effectiveness Network. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

Several study authors report receiving consulting fees from Amgen, Covance, Roche, Novartis, Sanofi, Merck, and Eli Lilly; grants and consulting fees from AbbVie, Janssen Pharmaceuticals, Hospira, Merck, Pfizer, Sanofi, and Novartis; and grants from Amgen, Eli Lilly, Celgene, Medexus, Medreleaf, Roche, and Union Chimique Belge.

Dr. McCormick reports a fellowship award from the Canadian Institutes of Health Research.

SOURCES: Tatangelo M et al. JAMA Netw Open. 2019;2(12):e1917053. doi: 10.1001/jamanetworkopen.2019.17053; McCormick N. JAMA Netw Open. 2019;2(12):e1917065. doi: 10.1001/jamanetworkopen.2019.17065

This story first appeared on Medscape.com.

The length of time a patient with rheumatoid arthritis takes a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate before switching to a biologic DMARD varies widely, and the variation is largely related to differences in prescriber preference, researchers say.

They found that 65% of the variation was attributed to differences between prescribers rather than patient variables. Another 4.6% was associated with regional differences in biologic DMARD use, and 30.4% of the variation was unexplained.

“Although disparities in access to biologic DMARDs increased in this study, the overall prescription percentage decreased relative to the population of active medication users with RA. This suggests that despite rheumatologists prescribing fewer biologic DMARDs on average per patient per unit of time, variations in the prescription of biologic DMARDs continue to grow,” the researchers explain.

The clinical implications of these differences in prescriber preferences are unclear, but the findings “show that between-prescriber differences exist in health care delivery for patients with RA, despite identical health insurance coverage,” they continue.

Mark Tatangelo of the University of Toronto and colleagues published their findings online Dec. 6, 2019, in JAMA Network Open.

They examined factors associated with the length of time from first csDMARD to receipt of first biologic in a retrospective cohort study using administrative data for 17,672 patients with RA and identical single-payer health insurance coverage in Ontario.

Patients were aged 67 years or older, had incident RA, and had received at least one csDMARD. The observation window was 2002 to 2015. During the study 719 patients (4.1%) received a first biologic DMARD. The primary outcome was time from first csDMARD to receipt of first biologic DMARD.

In an invited commentary, Natalie McCormick, PhD, from the clinical epidemiology program at Massachusetts General Hospital in Boston, writes: “A distinctive feature of the report by Tatangelo et al. was the emphasis on longer time to initiation of biologic therapy as an ideal outcome.”

Factors associated with a quicker move from csDMARDs to biologic DMARDs included younger age, female sex, living in an urban area close to prescribers, and longer disease duration. The shift to biologic DMARDs was also earlier for prescribers who were more recent graduates, in urban areas, and in areas with a greater supply of rheumatologists.

Dr. McCormick suggests that the association between earlier biologic DMARD use and higher concentration of rheumatologists might indicate that “peer effects” influence prescribing decisions.

Factors associated with a more prolonged time on csDMARDs before beginning a biologic DMARD included older age, male sex, and distance to the nearest rheumatologist.

Immigrants born outside of Canada were 41% less likely to have begun biologic DMARDs. “While its mechanism and implications warrant further investigation, this finding is novel and compelling, and it could become increasingly important,” Dr. McCormick writes.

The variation in highest biologic DMARD use, compared with lowest use among the regions in Ontario rose from 1.8% in 2002 to 8.7% in 2015. In models adjusted for age, sex, calendar year, and all patient and physician covariates, regional differences accounted for 4.6% of the variation in biologic DMARD prescription.

“A 4.6% difference in time to receipt of biologic DMARDs between regions should be considered problematic in the absence of other explanatory factors,” the authors write. “For example, every 1% increase in biologic prescriptions among a population of 72,000 funded patients with RA costs approximately CaD $10.8 million (U.S. $8.25 million) per year (assuming 10% biologics penetration and CaD $15,000 annually per biologic DMARD prescription [U.S. $11,460]).”

They explain that reducing the highest spending region in Ontario to the average spend would save approximately CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million) per year, whereas increasing biologic use in the underserved regions to the population average would cost about CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million).

Dr. McCormick writes that both undertreatment and overtreatment need more study and adds that the age gradient identified in this study “may reflect an ongoing bias against prescribing biologic DMARDs to elderly patients, despite a lack of evidence that older patients have a higher risk of infections or other adverse events.”

Dr. McCormick and the researchers emphasize that the decision to begin biologic DMARDs should not be taken lightly. “[S]mall changes in time to first biologic DMARD have major clinical and economic impacts. From a clinical perspective, the prescription of a biologic DMARD represents a transition to a more complex care plan, with less data to support the next prescription choice after the first biologic DMARD,” the authors warn.

This study was funded by grants from the Canadian Institute of Health Research, the Arthritis Society, the Ontario Drug Policy Research and Effectiveness Network, and the Canadian Institute of Health Research Drug Safety and Effectiveness Network. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

Several study authors report receiving consulting fees from Amgen, Covance, Roche, Novartis, Sanofi, Merck, and Eli Lilly; grants and consulting fees from AbbVie, Janssen Pharmaceuticals, Hospira, Merck, Pfizer, Sanofi, and Novartis; and grants from Amgen, Eli Lilly, Celgene, Medexus, Medreleaf, Roche, and Union Chimique Belge.

Dr. McCormick reports a fellowship award from the Canadian Institutes of Health Research.

SOURCES: Tatangelo M et al. JAMA Netw Open. 2019;2(12):e1917053. doi: 10.1001/jamanetworkopen.2019.17053; McCormick N. JAMA Netw Open. 2019;2(12):e1917065. doi: 10.1001/jamanetworkopen.2019.17065

This story first appeared on Medscape.com.

The length of time a patient with rheumatoid arthritis takes a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate before switching to a biologic DMARD varies widely, and the variation is largely related to differences in prescriber preference, researchers say.

They found that 65% of the variation was attributed to differences between prescribers rather than patient variables. Another 4.6% was associated with regional differences in biologic DMARD use, and 30.4% of the variation was unexplained.

“Although disparities in access to biologic DMARDs increased in this study, the overall prescription percentage decreased relative to the population of active medication users with RA. This suggests that despite rheumatologists prescribing fewer biologic DMARDs on average per patient per unit of time, variations in the prescription of biologic DMARDs continue to grow,” the researchers explain.

The clinical implications of these differences in prescriber preferences are unclear, but the findings “show that between-prescriber differences exist in health care delivery for patients with RA, despite identical health insurance coverage,” they continue.

Mark Tatangelo of the University of Toronto and colleagues published their findings online Dec. 6, 2019, in JAMA Network Open.

They examined factors associated with the length of time from first csDMARD to receipt of first biologic in a retrospective cohort study using administrative data for 17,672 patients with RA and identical single-payer health insurance coverage in Ontario.

Patients were aged 67 years or older, had incident RA, and had received at least one csDMARD. The observation window was 2002 to 2015. During the study 719 patients (4.1%) received a first biologic DMARD. The primary outcome was time from first csDMARD to receipt of first biologic DMARD.

In an invited commentary, Natalie McCormick, PhD, from the clinical epidemiology program at Massachusetts General Hospital in Boston, writes: “A distinctive feature of the report by Tatangelo et al. was the emphasis on longer time to initiation of biologic therapy as an ideal outcome.”

Factors associated with a quicker move from csDMARDs to biologic DMARDs included younger age, female sex, living in an urban area close to prescribers, and longer disease duration. The shift to biologic DMARDs was also earlier for prescribers who were more recent graduates, in urban areas, and in areas with a greater supply of rheumatologists.

Dr. McCormick suggests that the association between earlier biologic DMARD use and higher concentration of rheumatologists might indicate that “peer effects” influence prescribing decisions.

Factors associated with a more prolonged time on csDMARDs before beginning a biologic DMARD included older age, male sex, and distance to the nearest rheumatologist.

Immigrants born outside of Canada were 41% less likely to have begun biologic DMARDs. “While its mechanism and implications warrant further investigation, this finding is novel and compelling, and it could become increasingly important,” Dr. McCormick writes.

The variation in highest biologic DMARD use, compared with lowest use among the regions in Ontario rose from 1.8% in 2002 to 8.7% in 2015. In models adjusted for age, sex, calendar year, and all patient and physician covariates, regional differences accounted for 4.6% of the variation in biologic DMARD prescription.

“A 4.6% difference in time to receipt of biologic DMARDs between regions should be considered problematic in the absence of other explanatory factors,” the authors write. “For example, every 1% increase in biologic prescriptions among a population of 72,000 funded patients with RA costs approximately CaD $10.8 million (U.S. $8.25 million) per year (assuming 10% biologics penetration and CaD $15,000 annually per biologic DMARD prescription [U.S. $11,460]).”

They explain that reducing the highest spending region in Ontario to the average spend would save approximately CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million) per year, whereas increasing biologic use in the underserved regions to the population average would cost about CaD $6 million to $8 million (U.S. $4.6 million to $6.1 million).

Dr. McCormick writes that both undertreatment and overtreatment need more study and adds that the age gradient identified in this study “may reflect an ongoing bias against prescribing biologic DMARDs to elderly patients, despite a lack of evidence that older patients have a higher risk of infections or other adverse events.”

Dr. McCormick and the researchers emphasize that the decision to begin biologic DMARDs should not be taken lightly. “[S]mall changes in time to first biologic DMARD have major clinical and economic impacts. From a clinical perspective, the prescription of a biologic DMARD represents a transition to a more complex care plan, with less data to support the next prescription choice after the first biologic DMARD,” the authors warn.

This study was funded by grants from the Canadian Institute of Health Research, the Arthritis Society, the Ontario Drug Policy Research and Effectiveness Network, and the Canadian Institute of Health Research Drug Safety and Effectiveness Network. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

Several study authors report receiving consulting fees from Amgen, Covance, Roche, Novartis, Sanofi, Merck, and Eli Lilly; grants and consulting fees from AbbVie, Janssen Pharmaceuticals, Hospira, Merck, Pfizer, Sanofi, and Novartis; and grants from Amgen, Eli Lilly, Celgene, Medexus, Medreleaf, Roche, and Union Chimique Belge.

Dr. McCormick reports a fellowship award from the Canadian Institutes of Health Research.

SOURCES: Tatangelo M et al. JAMA Netw Open. 2019;2(12):e1917053. doi: 10.1001/jamanetworkopen.2019.17053; McCormick N. JAMA Netw Open. 2019;2(12):e1917065. doi: 10.1001/jamanetworkopen.2019.17065

This story first appeared on Medscape.com.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

cpalmer@mdedge.com

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

cpalmer@mdedge.com

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

cpalmer@mdedge.com

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

bjancin@mdedge.com

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

bjancin@mdedge.com

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

bjancin@mdedge.com

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.