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Secukinumab receives FDA approval for psoriatic arthritis, ankylosing spondylitis
The Food and Drug Administration approved two new indications for the interleukin-17A inhibitor secukinumab (Cosentyx) – psoriatic arthritis in adults and ankylosing spondylitis in adults – on Jan. 15. These join the approval for moderate to severe plaque psoriasis in adults it received in January 2015, according to an announcement from the drug’s manufacturer, Novartis.
The approvals are based on the efficacy and safety outcomes from four placebo-controlled, phase III studies, which included more than 1,500 adult patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) who were biologic treatment naive or had an inadequate response or were intolerant to anti-TNF agents.
Pivotal phase III studies in the secukinumab clinical trial program, which provided key data for the submission, were MEASURE 1 and MEASURE 2 involving 590 patients with AS, and FUTURE 1 and FUTURE 2 involving 1,003 patients with PsA. Novartis continues to investigate the fully human monoclonal antibody against IL-17A for its potential in preventing radiographic progression of spinal and joint structural damage in AS and PsA patients, respectively.
The European Medicines Agency approved secukinumab for PsA and AS in November 2015.
The Food and Drug Administration approved two new indications for the interleukin-17A inhibitor secukinumab (Cosentyx) – psoriatic arthritis in adults and ankylosing spondylitis in adults – on Jan. 15. These join the approval for moderate to severe plaque psoriasis in adults it received in January 2015, according to an announcement from the drug’s manufacturer, Novartis.
The approvals are based on the efficacy and safety outcomes from four placebo-controlled, phase III studies, which included more than 1,500 adult patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) who were biologic treatment naive or had an inadequate response or were intolerant to anti-TNF agents.
Pivotal phase III studies in the secukinumab clinical trial program, which provided key data for the submission, were MEASURE 1 and MEASURE 2 involving 590 patients with AS, and FUTURE 1 and FUTURE 2 involving 1,003 patients with PsA. Novartis continues to investigate the fully human monoclonal antibody against IL-17A for its potential in preventing radiographic progression of spinal and joint structural damage in AS and PsA patients, respectively.
The European Medicines Agency approved secukinumab for PsA and AS in November 2015.
The Food and Drug Administration approved two new indications for the interleukin-17A inhibitor secukinumab (Cosentyx) – psoriatic arthritis in adults and ankylosing spondylitis in adults – on Jan. 15. These join the approval for moderate to severe plaque psoriasis in adults it received in January 2015, according to an announcement from the drug’s manufacturer, Novartis.
The approvals are based on the efficacy and safety outcomes from four placebo-controlled, phase III studies, which included more than 1,500 adult patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) who were biologic treatment naive or had an inadequate response or were intolerant to anti-TNF agents.
Pivotal phase III studies in the secukinumab clinical trial program, which provided key data for the submission, were MEASURE 1 and MEASURE 2 involving 590 patients with AS, and FUTURE 1 and FUTURE 2 involving 1,003 patients with PsA. Novartis continues to investigate the fully human monoclonal antibody against IL-17A for its potential in preventing radiographic progression of spinal and joint structural damage in AS and PsA patients, respectively.
The European Medicines Agency approved secukinumab for PsA and AS in November 2015.
EADV: Family history of cardiovascular disease is key in psoriasis patients
COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.
“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.
He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.
Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.
“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.
In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.
Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.
In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.
A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.
A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.
Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.
Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).
In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).
Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.
An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.
Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.
COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.
“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.
He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.
Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.
“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.
In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.
Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.
In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.
A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.
A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.
Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.
Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).
In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).
Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.
An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.
Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.
COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.
“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.
He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.
Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.
“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.
In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.
Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.
In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.
A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.
A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.
Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.
Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).
In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).
Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.
An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.
Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.
AT THE EADV CONGRESS
Key clinical point: A family history of cardiovascular disease takes on extra importance in assessing cardiovascular risk in young adult psoriasis patients.
Major finding: Danes with mild or severe psoriasis plus a family history of cardiovascular disease were respectively 28% and 62% more likely to have an early cardiovascular event than the general population. In contrast, Danish psoriasis patients without a positive family history were not at increased risk of a cardiovascular event.
Data source: A population-based study of 2.7 million Danish young adults, including more than 30,000 diagnosed with psoriasis in their 20s, who were followed for 15 years.
Disclosures: The presenter reported having no financial conflicts regarding this study, which was supported by Danish national research funding.
ACR: Sulfasalazine reduces TNFi antibodies but more poorly than methotrexate
SAN FRANCISCO – Sulfasalazine prevents formation of antibodies against tumor necrosis factor inhibitors, but probably not as well as methotrexate, according to a European study of 140 axial spondyloarthritis patients.
“The effect of sulfasalazine on the development of antidrug antibodies has not been studied before. Our initial hypothesis was that methotrexate would [reduce] antibody formation” because it’s been shown to do that before, but that “sulfasalazine would not. This was a surprise to us,” said senior investigator Dr. Alejandro Balsa, chief of rheumatology at La Paz University Hospital in Madrid.
The findings suggest that sulfasalazine, like methotrexate, might “prevent immunogenicity and, hence ... secondary failure of” a tumor necrosis factor inhibitor (TNFi), he said at the annual meeting of the American College of Rheumatology.
Thirty-one patients (22%) were on infliximab (Remicade) and 109 (78%) were on adalimumab (Humira) in the year-long study, which was conducted in Madrid and Amsterdam.
Of the 90 patients on TNFi monotherapy, 33 (37%) developed TNFi antibodies, including 3 of 13 (23%) on infliximab monotherapy and 30 of 77 (39%) on adalimumab alone. The difference was not statistically significant.
Of the 50 patients on concomitant therapy, antibodies against anti-TNF agents occurred in 6 of 35 on sulfasalazine (17%), including three cases on infliximab and three on adalimumab. There was just one antibody case in 15 patients on methotrexate (7%); the patient was on adalimumab.
The trend toward better antibody protection with methotrexate was, again, not significant, probably because of the small numbers in the study.
Methotrexate and sulfasalazine are not routinely prescribed for axial spondyloarthritis; patients were on them in the study to help with peripheral manifestations. The drugs only prevent antibodies if started before a TNFi. “Once patients develop anti-[TNF] antibodies,” it’s too late, Dr. Balsa noted.
Despite the promising results, he said there’s not enough data at this point to recommend routine pretreatment with methotrexate or sulfasalazine to prevent TNFi antibodies.
As expected, antibodies diminished the clinical effect of a TNFi. Less than a quarter of antibody patients, versus more than a half free from antibodies, reached the investigators’ mark for low disease activity at 1 year: clinical improvement plus a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score below 4 and normal C-reactive protein (P = .03).
Also at 1 year, patients on monotherapy had an overall BASDAI improvement of about 1 point on the 10-point scale. Patients on methotrexate gained an additional point or so (P = .04), while those on sulfasalazine gained about a half point extra (P = .16).
“We only saw significant improvements in patients treated with methotrexate, probably because 100% cotreated with methotrexate had free” serum TNFi “at 1 year, as compared with only 82% cotreated with sulfasalazine,” Dr. Balsa said.
Oddly, the investigators detected free serum TNFi at 1 year in 78 (87%) monotherapy patients, which was more than in those cotreated with sulfasalazine; he didn’t address the finding.
The mean BASDAI at baseline was 6. Ankylosing spondylitis was the most common diagnosis in the study. More than half the subjects were men, the majority of patients were HLA-B27 positive, and their mean disease duration was 11 years.
Dr. Balsa’s institution receives research funding from Pfizer, UCB, and Roche, and he receives speakers fees from those companies plus AbbVie, Merck, and Bristol-Myers Squibb. Other investigators disclosed financial ties to those or other companies.
SAN FRANCISCO – Sulfasalazine prevents formation of antibodies against tumor necrosis factor inhibitors, but probably not as well as methotrexate, according to a European study of 140 axial spondyloarthritis patients.
“The effect of sulfasalazine on the development of antidrug antibodies has not been studied before. Our initial hypothesis was that methotrexate would [reduce] antibody formation” because it’s been shown to do that before, but that “sulfasalazine would not. This was a surprise to us,” said senior investigator Dr. Alejandro Balsa, chief of rheumatology at La Paz University Hospital in Madrid.
The findings suggest that sulfasalazine, like methotrexate, might “prevent immunogenicity and, hence ... secondary failure of” a tumor necrosis factor inhibitor (TNFi), he said at the annual meeting of the American College of Rheumatology.
Thirty-one patients (22%) were on infliximab (Remicade) and 109 (78%) were on adalimumab (Humira) in the year-long study, which was conducted in Madrid and Amsterdam.
Of the 90 patients on TNFi monotherapy, 33 (37%) developed TNFi antibodies, including 3 of 13 (23%) on infliximab monotherapy and 30 of 77 (39%) on adalimumab alone. The difference was not statistically significant.
Of the 50 patients on concomitant therapy, antibodies against anti-TNF agents occurred in 6 of 35 on sulfasalazine (17%), including three cases on infliximab and three on adalimumab. There was just one antibody case in 15 patients on methotrexate (7%); the patient was on adalimumab.
The trend toward better antibody protection with methotrexate was, again, not significant, probably because of the small numbers in the study.
Methotrexate and sulfasalazine are not routinely prescribed for axial spondyloarthritis; patients were on them in the study to help with peripheral manifestations. The drugs only prevent antibodies if started before a TNFi. “Once patients develop anti-[TNF] antibodies,” it’s too late, Dr. Balsa noted.
Despite the promising results, he said there’s not enough data at this point to recommend routine pretreatment with methotrexate or sulfasalazine to prevent TNFi antibodies.
As expected, antibodies diminished the clinical effect of a TNFi. Less than a quarter of antibody patients, versus more than a half free from antibodies, reached the investigators’ mark for low disease activity at 1 year: clinical improvement plus a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score below 4 and normal C-reactive protein (P = .03).
Also at 1 year, patients on monotherapy had an overall BASDAI improvement of about 1 point on the 10-point scale. Patients on methotrexate gained an additional point or so (P = .04), while those on sulfasalazine gained about a half point extra (P = .16).
“We only saw significant improvements in patients treated with methotrexate, probably because 100% cotreated with methotrexate had free” serum TNFi “at 1 year, as compared with only 82% cotreated with sulfasalazine,” Dr. Balsa said.
Oddly, the investigators detected free serum TNFi at 1 year in 78 (87%) monotherapy patients, which was more than in those cotreated with sulfasalazine; he didn’t address the finding.
The mean BASDAI at baseline was 6. Ankylosing spondylitis was the most common diagnosis in the study. More than half the subjects were men, the majority of patients were HLA-B27 positive, and their mean disease duration was 11 years.
Dr. Balsa’s institution receives research funding from Pfizer, UCB, and Roche, and he receives speakers fees from those companies plus AbbVie, Merck, and Bristol-Myers Squibb. Other investigators disclosed financial ties to those or other companies.
SAN FRANCISCO – Sulfasalazine prevents formation of antibodies against tumor necrosis factor inhibitors, but probably not as well as methotrexate, according to a European study of 140 axial spondyloarthritis patients.
“The effect of sulfasalazine on the development of antidrug antibodies has not been studied before. Our initial hypothesis was that methotrexate would [reduce] antibody formation” because it’s been shown to do that before, but that “sulfasalazine would not. This was a surprise to us,” said senior investigator Dr. Alejandro Balsa, chief of rheumatology at La Paz University Hospital in Madrid.
The findings suggest that sulfasalazine, like methotrexate, might “prevent immunogenicity and, hence ... secondary failure of” a tumor necrosis factor inhibitor (TNFi), he said at the annual meeting of the American College of Rheumatology.
Thirty-one patients (22%) were on infliximab (Remicade) and 109 (78%) were on adalimumab (Humira) in the year-long study, which was conducted in Madrid and Amsterdam.
Of the 90 patients on TNFi monotherapy, 33 (37%) developed TNFi antibodies, including 3 of 13 (23%) on infliximab monotherapy and 30 of 77 (39%) on adalimumab alone. The difference was not statistically significant.
Of the 50 patients on concomitant therapy, antibodies against anti-TNF agents occurred in 6 of 35 on sulfasalazine (17%), including three cases on infliximab and three on adalimumab. There was just one antibody case in 15 patients on methotrexate (7%); the patient was on adalimumab.
The trend toward better antibody protection with methotrexate was, again, not significant, probably because of the small numbers in the study.
Methotrexate and sulfasalazine are not routinely prescribed for axial spondyloarthritis; patients were on them in the study to help with peripheral manifestations. The drugs only prevent antibodies if started before a TNFi. “Once patients develop anti-[TNF] antibodies,” it’s too late, Dr. Balsa noted.
Despite the promising results, he said there’s not enough data at this point to recommend routine pretreatment with methotrexate or sulfasalazine to prevent TNFi antibodies.
As expected, antibodies diminished the clinical effect of a TNFi. Less than a quarter of antibody patients, versus more than a half free from antibodies, reached the investigators’ mark for low disease activity at 1 year: clinical improvement plus a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score below 4 and normal C-reactive protein (P = .03).
Also at 1 year, patients on monotherapy had an overall BASDAI improvement of about 1 point on the 10-point scale. Patients on methotrexate gained an additional point or so (P = .04), while those on sulfasalazine gained about a half point extra (P = .16).
“We only saw significant improvements in patients treated with methotrexate, probably because 100% cotreated with methotrexate had free” serum TNFi “at 1 year, as compared with only 82% cotreated with sulfasalazine,” Dr. Balsa said.
Oddly, the investigators detected free serum TNFi at 1 year in 78 (87%) monotherapy patients, which was more than in those cotreated with sulfasalazine; he didn’t address the finding.
The mean BASDAI at baseline was 6. Ankylosing spondylitis was the most common diagnosis in the study. More than half the subjects were men, the majority of patients were HLA-B27 positive, and their mean disease duration was 11 years.
Dr. Balsa’s institution receives research funding from Pfizer, UCB, and Roche, and he receives speakers fees from those companies plus AbbVie, Merck, and Bristol-Myers Squibb. Other investigators disclosed financial ties to those or other companies.
AT THE ACR ANNUAL MEETING
Key clinical point: Pretreatment with sulfasalazine seems to prevent TNFi antibodies, but not as well as methotrexate.
Major finding: Antibodies against anti-TNF agents occurred in 6 of 35 on sulfasalazine (17%), including 3 cases on infliximab and 3 on adalimumab. There was just one antibody case in 15 patients on methotrexate (7%); the patient was on adalimumab.
Data source: European study of 140 axial spondyloarthritis patients
Disclosures: The senior investigator’s institution receives research funding from Pfizer, UCB, and Roche, and he receives speakers fees from those companies plus AbbVie, Merck, and Bristol-Myers Squibb. Other investigators disclosed financial ties to those or other companies.
ACR: The pain of inflammatory disease goes beyond the physical
SAN FRANCISCO – The most common fear of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) patients is that their future suffering will be as bad as their past suffering, according to a French survey of 474 patients.
Overall, 182 of the 303 RA patients (60%) and 122 of the 171 axSpA patients (71%) in the study ranked that fear as at least a 7 on a 10-point scale, and it remained a serious and common concern even among the roughly half of patients who were in remission.
Majorities in both groups were highly concerned about deformity, wheel chair dependence, burdening loved ones, losing autonomy, and disease spread to other joints. Less common fears, but still ranked at least a 7 by about one-third to well over half of patients, were more frequent flares, inability to care for others, losing friends, loss of treatment effectiveness, fear of treatment side effects, and not finding help if independence is lost.
In general, axSpA was perceived as the more frightening disease, with patients more likely than those with RA to give fears presented on the survey a score of 7 or higher; axSpA patients also were more likely to fear the impact of disease on pregnancy and work, and more worried about passing disease onto their children. Fears about joints seizing up, bone and spine fusion, and increased flare activity were far more prevalent in the axSpA group.
The findings are from a test run of a new questionnaire being developed in France to capture the psychological burden of chronic inflammatory disease. The idea is to make patients’ fears and convictions explicit so that providers know what they are and can help patients cope.
“We’ve had this idea for a long time. Patients have fears and beliefs that” are difficult to express, and they get in the way of effective office communication. The questionnaire might break down the walls, so “patients know their doctors understand and are concerned” about their overall well-being, said senior investigator Dr. Francis Berenbaum, chief of rheumatology at Saint Antoine Hospital in Paris.
It’s hoped that the efforts will improve trust and dialogue between patients and doctors and lead to better treatment adherence and follow-up, more effective counseling, and perhaps even new patient-related outcomes for clinical trials, he said at the annual meeting of the American College of Rheumatology.
To create the survey, the team conducted semi-structured patient interviews at rheumatology practices across France. They whittled the responses down to identify 23 common fears and 19 disease-related beliefs in RA and axSpA. The resulting 44-item survey – there are two additional items about pregnancy and work-related concerns – asks patients to rate each one on a scale of 1-10. The team hopes to have data soon to show whether or not the efforts improve outcomes.
Common beliefs in both groups were that fatigue, over-exertion, stress, and weather changes trigger flares, but that moderate physical activity reduces them.
Almost half of RA patients, versus about a quarter of axSpA patients, believed that their disease was triggered by an emotional shock or stressful event, and small minorities in both groups attributed their disease to pollution, vaccines, or passive or active smoking. About 70% of patients in both groups were on biologics, and about one-third in each were very worried that their treatments would cause cancer.
Some “disease perceptions may not be accurate” and “provide a basis for discussion … to dispel misconceptions, align treatment expectations, and provide reassurance,” the investigators noted,
The RA patients were 60 years old on average, and about three-quarters were women. The median disease duration was 10 years, and mean Disease Activity Score (DAS28) was 2.7; axSpA patients were a mean age of 47 years, 43% were women, and the median disease duration was 12 years. Their mean Bath Ankylosing Spondylitis Disease Activity Index score was 3.2.
Foundation Arthritis Jacques Courtin and UCB Pharma funded the work. Dr. Berenbaum has no relevant disclosures. Two investigators are UCB employees.
SAN FRANCISCO – The most common fear of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) patients is that their future suffering will be as bad as their past suffering, according to a French survey of 474 patients.
Overall, 182 of the 303 RA patients (60%) and 122 of the 171 axSpA patients (71%) in the study ranked that fear as at least a 7 on a 10-point scale, and it remained a serious and common concern even among the roughly half of patients who were in remission.
Majorities in both groups were highly concerned about deformity, wheel chair dependence, burdening loved ones, losing autonomy, and disease spread to other joints. Less common fears, but still ranked at least a 7 by about one-third to well over half of patients, were more frequent flares, inability to care for others, losing friends, loss of treatment effectiveness, fear of treatment side effects, and not finding help if independence is lost.
In general, axSpA was perceived as the more frightening disease, with patients more likely than those with RA to give fears presented on the survey a score of 7 or higher; axSpA patients also were more likely to fear the impact of disease on pregnancy and work, and more worried about passing disease onto their children. Fears about joints seizing up, bone and spine fusion, and increased flare activity were far more prevalent in the axSpA group.
The findings are from a test run of a new questionnaire being developed in France to capture the psychological burden of chronic inflammatory disease. The idea is to make patients’ fears and convictions explicit so that providers know what they are and can help patients cope.
“We’ve had this idea for a long time. Patients have fears and beliefs that” are difficult to express, and they get in the way of effective office communication. The questionnaire might break down the walls, so “patients know their doctors understand and are concerned” about their overall well-being, said senior investigator Dr. Francis Berenbaum, chief of rheumatology at Saint Antoine Hospital in Paris.
It’s hoped that the efforts will improve trust and dialogue between patients and doctors and lead to better treatment adherence and follow-up, more effective counseling, and perhaps even new patient-related outcomes for clinical trials, he said at the annual meeting of the American College of Rheumatology.
To create the survey, the team conducted semi-structured patient interviews at rheumatology practices across France. They whittled the responses down to identify 23 common fears and 19 disease-related beliefs in RA and axSpA. The resulting 44-item survey – there are two additional items about pregnancy and work-related concerns – asks patients to rate each one on a scale of 1-10. The team hopes to have data soon to show whether or not the efforts improve outcomes.
Common beliefs in both groups were that fatigue, over-exertion, stress, and weather changes trigger flares, but that moderate physical activity reduces them.
Almost half of RA patients, versus about a quarter of axSpA patients, believed that their disease was triggered by an emotional shock or stressful event, and small minorities in both groups attributed their disease to pollution, vaccines, or passive or active smoking. About 70% of patients in both groups were on biologics, and about one-third in each were very worried that their treatments would cause cancer.
Some “disease perceptions may not be accurate” and “provide a basis for discussion … to dispel misconceptions, align treatment expectations, and provide reassurance,” the investigators noted,
The RA patients were 60 years old on average, and about three-quarters were women. The median disease duration was 10 years, and mean Disease Activity Score (DAS28) was 2.7; axSpA patients were a mean age of 47 years, 43% were women, and the median disease duration was 12 years. Their mean Bath Ankylosing Spondylitis Disease Activity Index score was 3.2.
Foundation Arthritis Jacques Courtin and UCB Pharma funded the work. Dr. Berenbaum has no relevant disclosures. Two investigators are UCB employees.
SAN FRANCISCO – The most common fear of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) patients is that their future suffering will be as bad as their past suffering, according to a French survey of 474 patients.
Overall, 182 of the 303 RA patients (60%) and 122 of the 171 axSpA patients (71%) in the study ranked that fear as at least a 7 on a 10-point scale, and it remained a serious and common concern even among the roughly half of patients who were in remission.
Majorities in both groups were highly concerned about deformity, wheel chair dependence, burdening loved ones, losing autonomy, and disease spread to other joints. Less common fears, but still ranked at least a 7 by about one-third to well over half of patients, were more frequent flares, inability to care for others, losing friends, loss of treatment effectiveness, fear of treatment side effects, and not finding help if independence is lost.
In general, axSpA was perceived as the more frightening disease, with patients more likely than those with RA to give fears presented on the survey a score of 7 or higher; axSpA patients also were more likely to fear the impact of disease on pregnancy and work, and more worried about passing disease onto their children. Fears about joints seizing up, bone and spine fusion, and increased flare activity were far more prevalent in the axSpA group.
The findings are from a test run of a new questionnaire being developed in France to capture the psychological burden of chronic inflammatory disease. The idea is to make patients’ fears and convictions explicit so that providers know what they are and can help patients cope.
“We’ve had this idea for a long time. Patients have fears and beliefs that” are difficult to express, and they get in the way of effective office communication. The questionnaire might break down the walls, so “patients know their doctors understand and are concerned” about their overall well-being, said senior investigator Dr. Francis Berenbaum, chief of rheumatology at Saint Antoine Hospital in Paris.
It’s hoped that the efforts will improve trust and dialogue between patients and doctors and lead to better treatment adherence and follow-up, more effective counseling, and perhaps even new patient-related outcomes for clinical trials, he said at the annual meeting of the American College of Rheumatology.
To create the survey, the team conducted semi-structured patient interviews at rheumatology practices across France. They whittled the responses down to identify 23 common fears and 19 disease-related beliefs in RA and axSpA. The resulting 44-item survey – there are two additional items about pregnancy and work-related concerns – asks patients to rate each one on a scale of 1-10. The team hopes to have data soon to show whether or not the efforts improve outcomes.
Common beliefs in both groups were that fatigue, over-exertion, stress, and weather changes trigger flares, but that moderate physical activity reduces them.
Almost half of RA patients, versus about a quarter of axSpA patients, believed that their disease was triggered by an emotional shock or stressful event, and small minorities in both groups attributed their disease to pollution, vaccines, or passive or active smoking. About 70% of patients in both groups were on biologics, and about one-third in each were very worried that their treatments would cause cancer.
Some “disease perceptions may not be accurate” and “provide a basis for discussion … to dispel misconceptions, align treatment expectations, and provide reassurance,” the investigators noted,
The RA patients were 60 years old on average, and about three-quarters were women. The median disease duration was 10 years, and mean Disease Activity Score (DAS28) was 2.7; axSpA patients were a mean age of 47 years, 43% were women, and the median disease duration was 12 years. Their mean Bath Ankylosing Spondylitis Disease Activity Index score was 3.2.
Foundation Arthritis Jacques Courtin and UCB Pharma funded the work. Dr. Berenbaum has no relevant disclosures. Two investigators are UCB employees.
AT THE ACR ANNUAL MEETING
Key clinical point: Ask patients what they are worried about; you might put them at ease by addressing their misconceptions.
Major finding: Overall, 60% of RA patients and 71% of axSpA patients were fearful that their future suffering would be as bad as their past suffering.
Data source: A French survey of 474 patients.
Disclosures: Foundation Arthritis Jacques Courtin and UCB Pharma funded the study. The senior investigator has no relevant disclosures. Two investigators are UCB employees.
ACR: Etanercept during pregnancy doubles the odds of major malformations
SAN FRANCISCO – Etanercept during pregnancy more than doubled the risk of major congenital malformations in a study by the Organization of Teratology Information Specialists.
The group keeps a prospective registry on exposures to biologics during pregnancy. It is finishing up its adalimumab (Humira) investigation and hasn’t found much to worry about, and continues to gather data on abatacept (Orencia), tocilizumab (Actemra), tofacitinib (Xeljanz), apremilast (Otezla), and certolizumab pegol (Cimzia).
Etanercept (Enbrel), however, seems to be a different story; major malformations turned up in the group’s recently completed investigation. Even so, Organization of Teratology Information Specialists (OTIS) investigator Dr. Christina D. Chambers, Ph.D., of the University of California, San Diego, was careful to note at the annual meeting of the American College of Rheumatology that “etanercept is not meeting the criteria for causality. There’s no pattern” in major defects and “no biological plausibility” because the drug doesn’t seem to cross the placenta when the fetus is most vulnerable to adverse outcomes.
“It is difficult to draw the conclusion that this drug is causing harm. With true teratogens, you tend to see reduced birth weights and an increased risk of spontaneous abortion, which is not the case with etanercept. We are seeing only this one finding that kind of stands alone, and everything else looks pretty good,” she said.
The etanercept study investigated pregnancy outcomes in 370 women exposed to the drug while pregnant, mostly women with rheumatoid arthritis, but also women with psoriasis and ankylosing spondylitis. Their outcomes were compared with 164 pregnant women with the same diseases but no etanercept exposure – the disease control group – and 296 healthy pregnant women.
Women in all three groups were about 33 years old on average, and about 80% were white. The women were enrolled toward the end of their first trimester. Disease severity, comorbidities, and use of vitamins, alcohol, and tobacco were similar between etanercept and disease control women. About 40% of the etanercept and disease control women, but just one in the healthy pregnancy group, were exposed to systemic corticosteroids while pregnant.
There were 33 major structural defects in children born to women taking etanercept versus 7 in the disease control group. That translated to a more than doubling of risk with etanercept (odds ratio, 2.37; 95% confidence interval, 1.02-5.52), and a more than doubling of risk versus the 10 major structural defects in children born to healthy control women (OR, 2.91; 95% CI, 1.37-6.76).
A subanalysis excluded chromosomal anomalies, but “did not [change] our conclusions,” Dr. Chambers said.
Major structural defects generally refer to problems that need a surgical fix, including spina bifida, atrial septal defects, cleft palates, hypospadias, polydactyly, and craniosynostosis.
Minor defects that don’t need surgery, like a missing earlobe, occurred in six children exposed to etanercept and showed two different patterns that involved “three specific minor malformations” not seen in either of the control groups, Dr. Chambers said. She did not elaborate on what those patterns were, but noted that the parents usually had them, too, “suggesting a genetic component as opposed to a drug effect.”
Children in the three study groups had no statistically significant differences in 1-year malignancy rates, serious infections, and hospitalizations, even when exposed to etanercept in the third trimester.
Children exposed to etanercept, however, were more likely to be born preterm and more likely to be small for gestational age in weight, length, and head circumference. They were also more likely than disease control children to screen positive for developmental issues at 1 year, but none of those differences were statistically significant.
Dr. Chambers disclosed funding from 14 companies, including Amgen, the maker of etanercept, and Janssen, Pfizer, Roche, Sanofi/Genzyme, GlaxoSmithKline, and AbbVie, the maker of adalimumab.
SAN FRANCISCO – Etanercept during pregnancy more than doubled the risk of major congenital malformations in a study by the Organization of Teratology Information Specialists.
The group keeps a prospective registry on exposures to biologics during pregnancy. It is finishing up its adalimumab (Humira) investigation and hasn’t found much to worry about, and continues to gather data on abatacept (Orencia), tocilizumab (Actemra), tofacitinib (Xeljanz), apremilast (Otezla), and certolizumab pegol (Cimzia).
Etanercept (Enbrel), however, seems to be a different story; major malformations turned up in the group’s recently completed investigation. Even so, Organization of Teratology Information Specialists (OTIS) investigator Dr. Christina D. Chambers, Ph.D., of the University of California, San Diego, was careful to note at the annual meeting of the American College of Rheumatology that “etanercept is not meeting the criteria for causality. There’s no pattern” in major defects and “no biological plausibility” because the drug doesn’t seem to cross the placenta when the fetus is most vulnerable to adverse outcomes.
“It is difficult to draw the conclusion that this drug is causing harm. With true teratogens, you tend to see reduced birth weights and an increased risk of spontaneous abortion, which is not the case with etanercept. We are seeing only this one finding that kind of stands alone, and everything else looks pretty good,” she said.
The etanercept study investigated pregnancy outcomes in 370 women exposed to the drug while pregnant, mostly women with rheumatoid arthritis, but also women with psoriasis and ankylosing spondylitis. Their outcomes were compared with 164 pregnant women with the same diseases but no etanercept exposure – the disease control group – and 296 healthy pregnant women.
Women in all three groups were about 33 years old on average, and about 80% were white. The women were enrolled toward the end of their first trimester. Disease severity, comorbidities, and use of vitamins, alcohol, and tobacco were similar between etanercept and disease control women. About 40% of the etanercept and disease control women, but just one in the healthy pregnancy group, were exposed to systemic corticosteroids while pregnant.
There were 33 major structural defects in children born to women taking etanercept versus 7 in the disease control group. That translated to a more than doubling of risk with etanercept (odds ratio, 2.37; 95% confidence interval, 1.02-5.52), and a more than doubling of risk versus the 10 major structural defects in children born to healthy control women (OR, 2.91; 95% CI, 1.37-6.76).
A subanalysis excluded chromosomal anomalies, but “did not [change] our conclusions,” Dr. Chambers said.
Major structural defects generally refer to problems that need a surgical fix, including spina bifida, atrial septal defects, cleft palates, hypospadias, polydactyly, and craniosynostosis.
Minor defects that don’t need surgery, like a missing earlobe, occurred in six children exposed to etanercept and showed two different patterns that involved “three specific minor malformations” not seen in either of the control groups, Dr. Chambers said. She did not elaborate on what those patterns were, but noted that the parents usually had them, too, “suggesting a genetic component as opposed to a drug effect.”
Children in the three study groups had no statistically significant differences in 1-year malignancy rates, serious infections, and hospitalizations, even when exposed to etanercept in the third trimester.
Children exposed to etanercept, however, were more likely to be born preterm and more likely to be small for gestational age in weight, length, and head circumference. They were also more likely than disease control children to screen positive for developmental issues at 1 year, but none of those differences were statistically significant.
Dr. Chambers disclosed funding from 14 companies, including Amgen, the maker of etanercept, and Janssen, Pfizer, Roche, Sanofi/Genzyme, GlaxoSmithKline, and AbbVie, the maker of adalimumab.
SAN FRANCISCO – Etanercept during pregnancy more than doubled the risk of major congenital malformations in a study by the Organization of Teratology Information Specialists.
The group keeps a prospective registry on exposures to biologics during pregnancy. It is finishing up its adalimumab (Humira) investigation and hasn’t found much to worry about, and continues to gather data on abatacept (Orencia), tocilizumab (Actemra), tofacitinib (Xeljanz), apremilast (Otezla), and certolizumab pegol (Cimzia).
Etanercept (Enbrel), however, seems to be a different story; major malformations turned up in the group’s recently completed investigation. Even so, Organization of Teratology Information Specialists (OTIS) investigator Dr. Christina D. Chambers, Ph.D., of the University of California, San Diego, was careful to note at the annual meeting of the American College of Rheumatology that “etanercept is not meeting the criteria for causality. There’s no pattern” in major defects and “no biological plausibility” because the drug doesn’t seem to cross the placenta when the fetus is most vulnerable to adverse outcomes.
“It is difficult to draw the conclusion that this drug is causing harm. With true teratogens, you tend to see reduced birth weights and an increased risk of spontaneous abortion, which is not the case with etanercept. We are seeing only this one finding that kind of stands alone, and everything else looks pretty good,” she said.
The etanercept study investigated pregnancy outcomes in 370 women exposed to the drug while pregnant, mostly women with rheumatoid arthritis, but also women with psoriasis and ankylosing spondylitis. Their outcomes were compared with 164 pregnant women with the same diseases but no etanercept exposure – the disease control group – and 296 healthy pregnant women.
Women in all three groups were about 33 years old on average, and about 80% were white. The women were enrolled toward the end of their first trimester. Disease severity, comorbidities, and use of vitamins, alcohol, and tobacco were similar between etanercept and disease control women. About 40% of the etanercept and disease control women, but just one in the healthy pregnancy group, were exposed to systemic corticosteroids while pregnant.
There were 33 major structural defects in children born to women taking etanercept versus 7 in the disease control group. That translated to a more than doubling of risk with etanercept (odds ratio, 2.37; 95% confidence interval, 1.02-5.52), and a more than doubling of risk versus the 10 major structural defects in children born to healthy control women (OR, 2.91; 95% CI, 1.37-6.76).
A subanalysis excluded chromosomal anomalies, but “did not [change] our conclusions,” Dr. Chambers said.
Major structural defects generally refer to problems that need a surgical fix, including spina bifida, atrial septal defects, cleft palates, hypospadias, polydactyly, and craniosynostosis.
Minor defects that don’t need surgery, like a missing earlobe, occurred in six children exposed to etanercept and showed two different patterns that involved “three specific minor malformations” not seen in either of the control groups, Dr. Chambers said. She did not elaborate on what those patterns were, but noted that the parents usually had them, too, “suggesting a genetic component as opposed to a drug effect.”
Children in the three study groups had no statistically significant differences in 1-year malignancy rates, serious infections, and hospitalizations, even when exposed to etanercept in the third trimester.
Children exposed to etanercept, however, were more likely to be born preterm and more likely to be small for gestational age in weight, length, and head circumference. They were also more likely than disease control children to screen positive for developmental issues at 1 year, but none of those differences were statistically significant.
Dr. Chambers disclosed funding from 14 companies, including Amgen, the maker of etanercept, and Janssen, Pfizer, Roche, Sanofi/Genzyme, GlaxoSmithKline, and AbbVie, the maker of adalimumab.
AT THE ACR ANNUAL MEETING
Key clinical point: Although etanercept exposure was associated with more than twofold higher odds of major structural defects, there was no pattern to the defects and no biological plausibility to etanercept causing the defects.
Major finding: There were 33 major structural defects in children born to etanercept women versus 7 in a disease comparison group, translating to a more than doubling of risk with etanercept (OR, 2.37; 95% CI, 1.02-5.52).
Data source: Prospective investigation of 830 pregnant women.
Disclosures: The presenting investigator disclosed funding from 14 companies, including Amgen, the maker of etanercept, and AbbVie, the maker of adalimumab.
Methotrexate has a role in treating articular manifestations of psoriatic arthritis
Patients with psoriatic arthritis taking methotrexate demonstrated an improvement in peripheral joint disease, skin disease, enthesitis, dactylitis, and nail disease over 12 weeks in a subanalysis of methotrexate users in the TICOPA (Tight Control of Psoriatic Arthritis) study.
Out of the original 206 patients in the open-label, randomized, controlled TICOPA study, the subanalysis involved 188 who received methotrexate in its first 12 weeks. Substudy authors Dr. Laura C. Coates and Dr. Philip S. Helliwell of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds (England) verified a maximum dose at 12 weeks of at least 15 mg/week in 175, 20 mg/week in 122, and 25 mg/week in 86 (J Rheumatol. Dec 15. doi: 10.3899/jrheum.150614).
The proportions of patients achieving American College of Rheumatology (ACR) outcomes at 12 weeks were 40.8% for ACR20, 18.8% for ACR50, and 8.6% for ACR70. A total of 22.4% achieved minimal disease activity, defined as meeting five of these seven criteria: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area and Severity Index (PASI) of 1 or less or body surface area involvement of 3 or less, patient pain visual analog score (VAS) of 15 or less, patient global disease activity VAS of 20 or less, health assessment questionnaire of 0.5 or less, and 0-1 tender entheseal points.
Other improvements that occurred at 12 weeks included 27.2% reaching a PASI75, a 62.7% drop in dactylitis incidence, a significant drop of –59.7 in Leeds dactylitis instrument median score, and a significant decrease in the proportion of patients with enthesitis (25.7%). However, the median change in enthesitis score was 0.
Response rates did not differ between patients receiving methotrexate 15 mg/week or higher doses, although there was generally a higher proportion who met various response criteria among those taking greater than 15 mg/week. However, the authors noted that there could be an underestimation of the dose effect because the design of the TICOPA study, which randomized patients to a protocol for tight control of psoriatic arthritis disease activity or standard care, introduced a bias by intentionally escalating treatment doses in patients who continue to have active disease.
The investigators advised that the study results be interpreted in the context of the open-label design of the study, and placed alongside the other observational studies that support its use in psoriatic arthritis.
No relevant conflicts of interest were disclosed.
Patients with psoriatic arthritis taking methotrexate demonstrated an improvement in peripheral joint disease, skin disease, enthesitis, dactylitis, and nail disease over 12 weeks in a subanalysis of methotrexate users in the TICOPA (Tight Control of Psoriatic Arthritis) study.
Out of the original 206 patients in the open-label, randomized, controlled TICOPA study, the subanalysis involved 188 who received methotrexate in its first 12 weeks. Substudy authors Dr. Laura C. Coates and Dr. Philip S. Helliwell of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds (England) verified a maximum dose at 12 weeks of at least 15 mg/week in 175, 20 mg/week in 122, and 25 mg/week in 86 (J Rheumatol. Dec 15. doi: 10.3899/jrheum.150614).
The proportions of patients achieving American College of Rheumatology (ACR) outcomes at 12 weeks were 40.8% for ACR20, 18.8% for ACR50, and 8.6% for ACR70. A total of 22.4% achieved minimal disease activity, defined as meeting five of these seven criteria: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area and Severity Index (PASI) of 1 or less or body surface area involvement of 3 or less, patient pain visual analog score (VAS) of 15 or less, patient global disease activity VAS of 20 or less, health assessment questionnaire of 0.5 or less, and 0-1 tender entheseal points.
Other improvements that occurred at 12 weeks included 27.2% reaching a PASI75, a 62.7% drop in dactylitis incidence, a significant drop of –59.7 in Leeds dactylitis instrument median score, and a significant decrease in the proportion of patients with enthesitis (25.7%). However, the median change in enthesitis score was 0.
Response rates did not differ between patients receiving methotrexate 15 mg/week or higher doses, although there was generally a higher proportion who met various response criteria among those taking greater than 15 mg/week. However, the authors noted that there could be an underestimation of the dose effect because the design of the TICOPA study, which randomized patients to a protocol for tight control of psoriatic arthritis disease activity or standard care, introduced a bias by intentionally escalating treatment doses in patients who continue to have active disease.
The investigators advised that the study results be interpreted in the context of the open-label design of the study, and placed alongside the other observational studies that support its use in psoriatic arthritis.
No relevant conflicts of interest were disclosed.
Patients with psoriatic arthritis taking methotrexate demonstrated an improvement in peripheral joint disease, skin disease, enthesitis, dactylitis, and nail disease over 12 weeks in a subanalysis of methotrexate users in the TICOPA (Tight Control of Psoriatic Arthritis) study.
Out of the original 206 patients in the open-label, randomized, controlled TICOPA study, the subanalysis involved 188 who received methotrexate in its first 12 weeks. Substudy authors Dr. Laura C. Coates and Dr. Philip S. Helliwell of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds (England) verified a maximum dose at 12 weeks of at least 15 mg/week in 175, 20 mg/week in 122, and 25 mg/week in 86 (J Rheumatol. Dec 15. doi: 10.3899/jrheum.150614).
The proportions of patients achieving American College of Rheumatology (ACR) outcomes at 12 weeks were 40.8% for ACR20, 18.8% for ACR50, and 8.6% for ACR70. A total of 22.4% achieved minimal disease activity, defined as meeting five of these seven criteria: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area and Severity Index (PASI) of 1 or less or body surface area involvement of 3 or less, patient pain visual analog score (VAS) of 15 or less, patient global disease activity VAS of 20 or less, health assessment questionnaire of 0.5 or less, and 0-1 tender entheseal points.
Other improvements that occurred at 12 weeks included 27.2% reaching a PASI75, a 62.7% drop in dactylitis incidence, a significant drop of –59.7 in Leeds dactylitis instrument median score, and a significant decrease in the proportion of patients with enthesitis (25.7%). However, the median change in enthesitis score was 0.
Response rates did not differ between patients receiving methotrexate 15 mg/week or higher doses, although there was generally a higher proportion who met various response criteria among those taking greater than 15 mg/week. However, the authors noted that there could be an underestimation of the dose effect because the design of the TICOPA study, which randomized patients to a protocol for tight control of psoriatic arthritis disease activity or standard care, introduced a bias by intentionally escalating treatment doses in patients who continue to have active disease.
The investigators advised that the study results be interpreted in the context of the open-label design of the study, and placed alongside the other observational studies that support its use in psoriatic arthritis.
No relevant conflicts of interest were disclosed.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point: Methotrexate is a commonly prescribed drug in psoriatic arthritis, and while it may not be effective for all patients, it does have a role in the treatment of articular manifestations.
Major finding: The proportions of patients achieving American College of Rheumatology (ACR) outcomes at 12 weeks were 40.8% for ACR20, 18.8% for ACR50, and 8.6% for ACR70.
Data source: Open-label, observational study of 188 patients participating in the Tight Control of Psoriatic Arthritis (TICOPA) study.
Disclosures: No relevant conflicts of interest were disclosed.
More comorbidity with PsA form of spondyloarthritis
Psoriatic arthritis in patients with spondyloarthritis conveys an increased risk of comorbidities, especially cardiovascular and metabolic diseases, as compared with spondyloarthritis alone.
The association persisted even after adjusting for demographic factors, disease duration, and length of treatment, Dr. Naba Haque of the University of Leuven (Belgium) and associates wrote in the Journal of Rheumatology (2015 Dec 15. doi: 10.3899/jrheum.141359).
In an analysis of 518 patients in the spondyloarthritis database at the university, over half (54%) had comorbidities, and those with psoriatic spondyloarthropathy had significantly more comorbidities than those without psoriatic arthropathy (P less than .001). Cardiovascular comorbidities were most common, with an increased prevalence of hypertension, coronary artery disease, and hyperlipidemia in the patients with psoriatic spondyloarthropathy (odds ratios, 1.81, 1.39, and 1.60, respectively; P less than .001). The differences persisted after adjusting for confounders such as age, sex, disease duration, and treatment.
Twice as many patients with spondyloarthritis and psoriatic arthropathy met the criteria for metabolic syndrome as did patients without psoriatric arthropathy (10% vs. 5%, P = .03). The regression model showed a significant difference in the prevalence of diabetes in the PsA patients (OR, 1.35; 95% confidence interval, 1.17-1.56; P less than .001). Psoriatic arthropathy also was linked to an increased risk of cancer (12% vs. 6%; P less than .05); however, the authors wrote that “we can only state a possible positive association … this observation needs to be studied in further detail.”
The study was supported by an unrestricted grant from the Abbvie Chair for psoriatic arthritis research (Dr. Rik J. Lories and Dr. Kurt de Vlam).
Psoriatic arthritis in patients with spondyloarthritis conveys an increased risk of comorbidities, especially cardiovascular and metabolic diseases, as compared with spondyloarthritis alone.
The association persisted even after adjusting for demographic factors, disease duration, and length of treatment, Dr. Naba Haque of the University of Leuven (Belgium) and associates wrote in the Journal of Rheumatology (2015 Dec 15. doi: 10.3899/jrheum.141359).
In an analysis of 518 patients in the spondyloarthritis database at the university, over half (54%) had comorbidities, and those with psoriatic spondyloarthropathy had significantly more comorbidities than those without psoriatic arthropathy (P less than .001). Cardiovascular comorbidities were most common, with an increased prevalence of hypertension, coronary artery disease, and hyperlipidemia in the patients with psoriatic spondyloarthropathy (odds ratios, 1.81, 1.39, and 1.60, respectively; P less than .001). The differences persisted after adjusting for confounders such as age, sex, disease duration, and treatment.
Twice as many patients with spondyloarthritis and psoriatic arthropathy met the criteria for metabolic syndrome as did patients without psoriatric arthropathy (10% vs. 5%, P = .03). The regression model showed a significant difference in the prevalence of diabetes in the PsA patients (OR, 1.35; 95% confidence interval, 1.17-1.56; P less than .001). Psoriatic arthropathy also was linked to an increased risk of cancer (12% vs. 6%; P less than .05); however, the authors wrote that “we can only state a possible positive association … this observation needs to be studied in further detail.”
The study was supported by an unrestricted grant from the Abbvie Chair for psoriatic arthritis research (Dr. Rik J. Lories and Dr. Kurt de Vlam).
Psoriatic arthritis in patients with spondyloarthritis conveys an increased risk of comorbidities, especially cardiovascular and metabolic diseases, as compared with spondyloarthritis alone.
The association persisted even after adjusting for demographic factors, disease duration, and length of treatment, Dr. Naba Haque of the University of Leuven (Belgium) and associates wrote in the Journal of Rheumatology (2015 Dec 15. doi: 10.3899/jrheum.141359).
In an analysis of 518 patients in the spondyloarthritis database at the university, over half (54%) had comorbidities, and those with psoriatic spondyloarthropathy had significantly more comorbidities than those without psoriatic arthropathy (P less than .001). Cardiovascular comorbidities were most common, with an increased prevalence of hypertension, coronary artery disease, and hyperlipidemia in the patients with psoriatic spondyloarthropathy (odds ratios, 1.81, 1.39, and 1.60, respectively; P less than .001). The differences persisted after adjusting for confounders such as age, sex, disease duration, and treatment.
Twice as many patients with spondyloarthritis and psoriatic arthropathy met the criteria for metabolic syndrome as did patients without psoriatric arthropathy (10% vs. 5%, P = .03). The regression model showed a significant difference in the prevalence of diabetes in the PsA patients (OR, 1.35; 95% confidence interval, 1.17-1.56; P less than .001). Psoriatic arthropathy also was linked to an increased risk of cancer (12% vs. 6%; P less than .05); however, the authors wrote that “we can only state a possible positive association … this observation needs to be studied in further detail.”
The study was supported by an unrestricted grant from the Abbvie Chair for psoriatic arthritis research (Dr. Rik J. Lories and Dr. Kurt de Vlam).
FROM THE JOURNAL OF RHEUMATOLOGY
Key clinical point: People with psoriatic arthritis (PsA) have a significantly increased risk of cardiovascular and metabolic diseases, compared with people with non-PsA forms of spondyloarthritis (SpA).
Major finding: After correcting for risk factors, spondyloarthritis plus psoriatic arthritis was linked with an increased prevalence of hypertension, coronary artery disease, and hyperlipidemia (OR, 1.81, 1.39, and 1.60 respectively, P less than .001).
Data source: Cross-sectional study of 518 spondyloarthritis patients in a database at a university rheumatology department.
Disclosures: The study was supported by an unrestricted grant from the Abbvie Chair for psoriatic arthritis research (Dr. Lories and Dr. de Vlam).
Secukinumab cut ankylosing spondylitis symptoms in MEASURE trials
Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.
The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).
“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.
“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.
In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.
The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).
In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.
At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.
In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).
The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.
The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.
During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.
Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.
The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.
Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.
The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).
“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.
“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.
In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.
The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).
In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.
At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.
In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).
The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.
The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.
During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.
Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.
The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.
Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.
The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).
“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.
“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.
In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.
The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).
In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.
At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.
In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).
The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.
The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.
During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.
Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.
The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Interleukin-17A may play a role in ankylosing spondylitis, and secukinumab may prove to be an effective therapy for these patients.
Major finding: The primary endpoint of Assessment of Spondyloarthritis International Society (ASAS20) response rates at week 16 was met in both secukinumab groups in MEASURE 1 and in the group that received 150 mg of secukinumab subcutaneously in MEASURE 2.
Data source: Two double-blind, phase III studies: MEASURE 1 involving 371 patients with AS and MEASURE 2 involving 371 patients.
Disclosures: The studies were funded by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.
Poor response to third anti-TNF agent seen in most psoriatic arthritis patients
Patients with psoriatic arthritis who don’t respond to or cannot tolerate two different anti–tumor necrosis factor (TNF) agents are likely to respond poorly, if at all, to a third one, according to findings from a prospective, open-label, longitudinal study.
Dr. Lars Erik Kristensen of the department of rheumatology, Parker Institute, Copenhagen, and the department of rheumatology, Lund (Sweden) University Hospital, and his coinvestigators assessed treatment responses in patients treated at 11 European rheumatology centers during a 9-year period to build on the “rather sparse” data concerning second or third courses of anti-TNF treatment in psoriatic arthritis patients. “Our results suggest that other therapeutic options be considered after two courses of anti-TNF treatment have failed,” such as biological disease-modifying antirheumatic drugs that have different modes of action, they wrote.
The study participants were 217 patients with psoriatic arthritis who were switching from one anti-TNF agent to another and 57 who had tried two anti-TNF agents and were switching to a third. The drugs included etanercept, adalimumab, certolizumab pegol, golimumab, and infliximab.
In general, the treatment response rates among patients trying their second agent were markedly greater than those of patients trying their third. Nearly half (47%) of first-time switchers met the primary outcome measure – an ACR 20 response at 3 months – compared with only 22% of second-time switchers, the investigators said (J Rheumatol. 2015 Dec 1. doi: 10.3899/jrheum.150744).
The median drug survival (time on treatment) was 64 months for the first group, compared with only 14 months for the second group. The estimated 5-year drug survival was 51% for patients trying their second anti-TNF agent, compared with only 23% for patients trying their third.
This study was supported by the Osterlund Foundation, the Kock Foundation, the King Gustav V 80-Year Fund, Lund University Hospital, the Reumatikerforbundet, and the Oak Foundation. No information was available regarding Dr. Kristensen’s and his associates’ financial disclosures.
Patients with psoriatic arthritis who don’t respond to or cannot tolerate two different anti–tumor necrosis factor (TNF) agents are likely to respond poorly, if at all, to a third one, according to findings from a prospective, open-label, longitudinal study.
Dr. Lars Erik Kristensen of the department of rheumatology, Parker Institute, Copenhagen, and the department of rheumatology, Lund (Sweden) University Hospital, and his coinvestigators assessed treatment responses in patients treated at 11 European rheumatology centers during a 9-year period to build on the “rather sparse” data concerning second or third courses of anti-TNF treatment in psoriatic arthritis patients. “Our results suggest that other therapeutic options be considered after two courses of anti-TNF treatment have failed,” such as biological disease-modifying antirheumatic drugs that have different modes of action, they wrote.
The study participants were 217 patients with psoriatic arthritis who were switching from one anti-TNF agent to another and 57 who had tried two anti-TNF agents and were switching to a third. The drugs included etanercept, adalimumab, certolizumab pegol, golimumab, and infliximab.
In general, the treatment response rates among patients trying their second agent were markedly greater than those of patients trying their third. Nearly half (47%) of first-time switchers met the primary outcome measure – an ACR 20 response at 3 months – compared with only 22% of second-time switchers, the investigators said (J Rheumatol. 2015 Dec 1. doi: 10.3899/jrheum.150744).
The median drug survival (time on treatment) was 64 months for the first group, compared with only 14 months for the second group. The estimated 5-year drug survival was 51% for patients trying their second anti-TNF agent, compared with only 23% for patients trying their third.
This study was supported by the Osterlund Foundation, the Kock Foundation, the King Gustav V 80-Year Fund, Lund University Hospital, the Reumatikerforbundet, and the Oak Foundation. No information was available regarding Dr. Kristensen’s and his associates’ financial disclosures.
Patients with psoriatic arthritis who don’t respond to or cannot tolerate two different anti–tumor necrosis factor (TNF) agents are likely to respond poorly, if at all, to a third one, according to findings from a prospective, open-label, longitudinal study.
Dr. Lars Erik Kristensen of the department of rheumatology, Parker Institute, Copenhagen, and the department of rheumatology, Lund (Sweden) University Hospital, and his coinvestigators assessed treatment responses in patients treated at 11 European rheumatology centers during a 9-year period to build on the “rather sparse” data concerning second or third courses of anti-TNF treatment in psoriatic arthritis patients. “Our results suggest that other therapeutic options be considered after two courses of anti-TNF treatment have failed,” such as biological disease-modifying antirheumatic drugs that have different modes of action, they wrote.
The study participants were 217 patients with psoriatic arthritis who were switching from one anti-TNF agent to another and 57 who had tried two anti-TNF agents and were switching to a third. The drugs included etanercept, adalimumab, certolizumab pegol, golimumab, and infliximab.
In general, the treatment response rates among patients trying their second agent were markedly greater than those of patients trying their third. Nearly half (47%) of first-time switchers met the primary outcome measure – an ACR 20 response at 3 months – compared with only 22% of second-time switchers, the investigators said (J Rheumatol. 2015 Dec 1. doi: 10.3899/jrheum.150744).
The median drug survival (time on treatment) was 64 months for the first group, compared with only 14 months for the second group. The estimated 5-year drug survival was 51% for patients trying their second anti-TNF agent, compared with only 23% for patients trying their third.
This study was supported by the Osterlund Foundation, the Kock Foundation, the King Gustav V 80-Year Fund, Lund University Hospital, the Reumatikerforbundet, and the Oak Foundation. No information was available regarding Dr. Kristensen’s and his associates’ financial disclosures.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point: Patients with psoriatic arthritis who don’t respond to or cannot tolerate two different anti-TNF agents are likely to respond poorly, if at all, to a third one.
Major finding: 47% of first-time switchers met the primary outcome measure – an ACR 20 response at 3 months – compared with only 22% of second-time switchers.
Data source: A prospective, open-label, longitudinal study involving 217 patients who switched anti-TNF therapy once and 57 who switched twice during a 9-year period.
Disclosures: This study was supported by the Osterlund Foundation, the Kock Foundation, the King Gustav V 80-Year Fund, Lund University Hospital, the Reumatikerforbundet, and the Oak Foundation. No information was available regarding Dr. Kristensen’s and his associates’ financial disclosures.
Genetic differences may help predict progression of PsC to PsA
Dermatology researchers have uncovered differences in the genetic architecture of psoriatic arthritis (PsA) and cutaneous psoriasis (PsC).
Dr. Philip E. Stuart of the University of Michigan, Ann Arbor, and his colleagues from 32 institutions in the United States, Europe, and Canada, carried out a genome-wide association study (GWAS) of 1,430 patients with psoriatic arthritis and 1,417 healthy controls. They then combined results of their GWAS with five published studies of psoriasis associations (three GWASs and two targeted studies), comprising 3,061 psoriatic arthritis patients, 3,110 cutaneous-only psoriasis patients, and 9,273 psoriasis vulgaris patients, and 13,670 healthy controls of European descent.
The work, published in the American Journal of Human Genetics, identified five regions of significance in the PsA GWAS. These were all in known risk regions for PsA, with the strongest signals near HLA-B, IL12B, TRAF3IP2, TNIP1, and TYK2.
Looking across all studies, researchers detected 10 regions associated with PsA and 11 with PsC at genome-wide significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA, and TJFRSF9, LCE3C/B, TRAF3IP2, IL23A, and NFKBIA for PsC) had not previously achieved such significance. Researchers also identified a genetic variant associated with psoriasis vulgaris (PsV) near CDKAL1, and other variants that were more strongly associated with either PsA or PsC.
“These results provide insights into the pathogenic similarities and differences between PsC and PsA,” the authors wrote. Identifying the causative variants driving the observed associations “will aid prediction and therapy of psoriasis and its cutaneous and joint manifestations.”
Read the article in the American Journal of Human Genetics (2015 Dec 3;97:816-36).
Dermatology researchers have uncovered differences in the genetic architecture of psoriatic arthritis (PsA) and cutaneous psoriasis (PsC).
Dr. Philip E. Stuart of the University of Michigan, Ann Arbor, and his colleagues from 32 institutions in the United States, Europe, and Canada, carried out a genome-wide association study (GWAS) of 1,430 patients with psoriatic arthritis and 1,417 healthy controls. They then combined results of their GWAS with five published studies of psoriasis associations (three GWASs and two targeted studies), comprising 3,061 psoriatic arthritis patients, 3,110 cutaneous-only psoriasis patients, and 9,273 psoriasis vulgaris patients, and 13,670 healthy controls of European descent.
The work, published in the American Journal of Human Genetics, identified five regions of significance in the PsA GWAS. These were all in known risk regions for PsA, with the strongest signals near HLA-B, IL12B, TRAF3IP2, TNIP1, and TYK2.
Looking across all studies, researchers detected 10 regions associated with PsA and 11 with PsC at genome-wide significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA, and TJFRSF9, LCE3C/B, TRAF3IP2, IL23A, and NFKBIA for PsC) had not previously achieved such significance. Researchers also identified a genetic variant associated with psoriasis vulgaris (PsV) near CDKAL1, and other variants that were more strongly associated with either PsA or PsC.
“These results provide insights into the pathogenic similarities and differences between PsC and PsA,” the authors wrote. Identifying the causative variants driving the observed associations “will aid prediction and therapy of psoriasis and its cutaneous and joint manifestations.”
Read the article in the American Journal of Human Genetics (2015 Dec 3;97:816-36).
Dermatology researchers have uncovered differences in the genetic architecture of psoriatic arthritis (PsA) and cutaneous psoriasis (PsC).
Dr. Philip E. Stuart of the University of Michigan, Ann Arbor, and his colleagues from 32 institutions in the United States, Europe, and Canada, carried out a genome-wide association study (GWAS) of 1,430 patients with psoriatic arthritis and 1,417 healthy controls. They then combined results of their GWAS with five published studies of psoriasis associations (three GWASs and two targeted studies), comprising 3,061 psoriatic arthritis patients, 3,110 cutaneous-only psoriasis patients, and 9,273 psoriasis vulgaris patients, and 13,670 healthy controls of European descent.
The work, published in the American Journal of Human Genetics, identified five regions of significance in the PsA GWAS. These were all in known risk regions for PsA, with the strongest signals near HLA-B, IL12B, TRAF3IP2, TNIP1, and TYK2.
Looking across all studies, researchers detected 10 regions associated with PsA and 11 with PsC at genome-wide significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA, and TJFRSF9, LCE3C/B, TRAF3IP2, IL23A, and NFKBIA for PsC) had not previously achieved such significance. Researchers also identified a genetic variant associated with psoriasis vulgaris (PsV) near CDKAL1, and other variants that were more strongly associated with either PsA or PsC.
“These results provide insights into the pathogenic similarities and differences between PsC and PsA,” the authors wrote. Identifying the causative variants driving the observed associations “will aid prediction and therapy of psoriasis and its cutaneous and joint manifestations.”
Read the article in the American Journal of Human Genetics (2015 Dec 3;97:816-36).
FROM AMERICAN JOURNAL OF HUMAN GENETICS
