Spondyloarthropathies

Heavy alcohol consumption was associated with incident psoriatic arthritis in women, Shaowei Wu, Ph.D., and his associates reported in a study of 116,430 female registered nurses in the Nurses’ Health Study II.

The investigators found 141 incident cases of psoriatic arthritis (PsA) during 1,137,763 years of follow-up in 1991-2005. The risk for PsA was not signficantly different between drinkers and nondrinkers for women who consumed 0.1-14.9 g/day (hazard ratio, 0.7) or 15-29.9 g/day (HR, 1.43), but women who consumed more than 30 g/day had a signficantly elevated risk (HR, 4.45). The results remained consistent when updated alcohol intake and 1991 baseline consumption was used, and when the analysis was restricted to those who developed psoriasis during follow-up.

“These findings are also in line with the biological evidence that high levels of alcohol intake contribute to systemic inflammation and may trigger psoriatic eruption, and thus may have important implications for the prevention of PsA,” the investigators concluded.

Find the full study in the Journal of Rheumatology (doi:10.3899/jrheum.140808).

Heavy alcohol consumption was associated with incident psoriatic arthritis in women, Shaowei Wu, Ph.D., and his associates reported in a study of 116,430 female registered nurses in the Nurses’ Health Study II.

The investigators found 141 incident cases of psoriatic arthritis (PsA) during 1,137,763 years of follow-up in 1991-2005. The risk for PsA was not signficantly different between drinkers and nondrinkers for women who consumed 0.1-14.9 g/day (hazard ratio, 0.7) or 15-29.9 g/day (HR, 1.43), but women who consumed more than 30 g/day had a signficantly elevated risk (HR, 4.45). The results remained consistent when updated alcohol intake and 1991 baseline consumption was used, and when the analysis was restricted to those who developed psoriasis during follow-up.

“These findings are also in line with the biological evidence that high levels of alcohol intake contribute to systemic inflammation and may trigger psoriatic eruption, and thus may have important implications for the prevention of PsA,” the investigators concluded.

Find the full study in the Journal of Rheumatology (doi:10.3899/jrheum.140808).

Heavy alcohol consumption was associated with incident psoriatic arthritis in women, Shaowei Wu, Ph.D., and his associates reported in a study of 116,430 female registered nurses in the Nurses’ Health Study II.

The investigators found 141 incident cases of psoriatic arthritis (PsA) during 1,137,763 years of follow-up in 1991-2005. The risk for PsA was not signficantly different between drinkers and nondrinkers for women who consumed 0.1-14.9 g/day (hazard ratio, 0.7) or 15-29.9 g/day (HR, 1.43), but women who consumed more than 30 g/day had a signficantly elevated risk (HR, 4.45). The results remained consistent when updated alcohol intake and 1991 baseline consumption was used, and when the analysis was restricted to those who developed psoriasis during follow-up.

“These findings are also in line with the biological evidence that high levels of alcohol intake contribute to systemic inflammation and may trigger psoriatic eruption, and thus may have important implications for the prevention of PsA,” the investigators concluded.

Find the full study in the Journal of Rheumatology (doi:10.3899/jrheum.140808).

SAN FRANCISCO – Apremilast met its primary endpoint at week 32 with no new or serious safety signals among patients with moderate to severe plaque psoriasis, according to phase III data from the ongoing LIBERATE study.

At week 16, 40% of patients who received oral apremilast achieved PASI-75, compared with 12% of the placebo group, Dr. Kristian Reich reported at the annual meeting of the American Academy of Dermatology.

By week 32, PASI-75 response for apremilast had further risen to 53%, he added. “This drug may not be a quick fix, but the longer you give it, the higher the response,” said Dr. Reich of SCIderm Research Institute and Dermatologikum Hamburg in Germany.

The randomized, double-blind LIBERATE study compared the safety and efficacy of apremilast (30 mg twice daily) and injectable etanercept (50 mg weekly) with placebo among 250 patients with plaque psoriasis who had not previously received biologic therapy. Patients received one of the three treatments through week 16, and then all were switched to or continued apremilast.

At week 16, PASI-75 response rates were 40% for apremilast, 48% for etanercept, and 12% for placebo (P < .0001 for apremilast versus placebo), reported Dr. Reich. The high rate of response to placebo might have occurred because patients in the study were treatment naive, he said. At week 32, PASI-75 response rates were 53% for patients who received apremilast from baseline, and 61% for patients who switched from etanercept to apremilast at week 16.

Based on the results, “I would probably use apremilast more in the moderate [psoriasis] space than in the severe space, but its efficacy does not correlate with baseline disease severity, as far as I know,” said Dr. Reich. Apremilast also beat placebo in analyses of secondary endpoints, including static physician global assessment of clear or almost clear and the Dermatology Quality of Life Index, he added.

Safety analyses showed that the drug was generally well tolerated. Fewer than 4% of patients discontinued treatment because of adverse events, the most common of which were diarrhea, nausea, vomiting, and headache (including tension headache). No new side effects emerged after patients switched from etanercept to apremilast at week 16, he said.

A post hoc analysis found that apremilast was noninferior to etanercept (P > .05) in terms of PASI-75, although the study was not powered to directly compare the two biologics, Dr. Reich noted.

Celgene Corporation makes apremilast and sponsored the study. Dr. Reich reported serving as a speaker for and receiving honoraria from Celgene.

SAN FRANCISCO – Apremilast met its primary endpoint at week 32 with no new or serious safety signals among patients with moderate to severe plaque psoriasis, according to phase III data from the ongoing LIBERATE study.

At week 16, 40% of patients who received oral apremilast achieved PASI-75, compared with 12% of the placebo group, Dr. Kristian Reich reported at the annual meeting of the American Academy of Dermatology.

By week 32, PASI-75 response for apremilast had further risen to 53%, he added. “This drug may not be a quick fix, but the longer you give it, the higher the response,” said Dr. Reich of SCIderm Research Institute and Dermatologikum Hamburg in Germany.

The randomized, double-blind LIBERATE study compared the safety and efficacy of apremilast (30 mg twice daily) and injectable etanercept (50 mg weekly) with placebo among 250 patients with plaque psoriasis who had not previously received biologic therapy. Patients received one of the three treatments through week 16, and then all were switched to or continued apremilast.

At week 16, PASI-75 response rates were 40% for apremilast, 48% for etanercept, and 12% for placebo (P < .0001 for apremilast versus placebo), reported Dr. Reich. The high rate of response to placebo might have occurred because patients in the study were treatment naive, he said. At week 32, PASI-75 response rates were 53% for patients who received apremilast from baseline, and 61% for patients who switched from etanercept to apremilast at week 16.

Based on the results, “I would probably use apremilast more in the moderate [psoriasis] space than in the severe space, but its efficacy does not correlate with baseline disease severity, as far as I know,” said Dr. Reich. Apremilast also beat placebo in analyses of secondary endpoints, including static physician global assessment of clear or almost clear and the Dermatology Quality of Life Index, he added.

Safety analyses showed that the drug was generally well tolerated. Fewer than 4% of patients discontinued treatment because of adverse events, the most common of which were diarrhea, nausea, vomiting, and headache (including tension headache). No new side effects emerged after patients switched from etanercept to apremilast at week 16, he said.

A post hoc analysis found that apremilast was noninferior to etanercept (P > .05) in terms of PASI-75, although the study was not powered to directly compare the two biologics, Dr. Reich noted.

Celgene Corporation makes apremilast and sponsored the study. Dr. Reich reported serving as a speaker for and receiving honoraria from Celgene.

SAN FRANCISCO – Apremilast met its primary endpoint at week 32 with no new or serious safety signals among patients with moderate to severe plaque psoriasis, according to phase III data from the ongoing LIBERATE study.

At week 16, 40% of patients who received oral apremilast achieved PASI-75, compared with 12% of the placebo group, Dr. Kristian Reich reported at the annual meeting of the American Academy of Dermatology.

By week 32, PASI-75 response for apremilast had further risen to 53%, he added. “This drug may not be a quick fix, but the longer you give it, the higher the response,” said Dr. Reich of SCIderm Research Institute and Dermatologikum Hamburg in Germany.

The randomized, double-blind LIBERATE study compared the safety and efficacy of apremilast (30 mg twice daily) and injectable etanercept (50 mg weekly) with placebo among 250 patients with plaque psoriasis who had not previously received biologic therapy. Patients received one of the three treatments through week 16, and then all were switched to or continued apremilast.

At week 16, PASI-75 response rates were 40% for apremilast, 48% for etanercept, and 12% for placebo (P < .0001 for apremilast versus placebo), reported Dr. Reich. The high rate of response to placebo might have occurred because patients in the study were treatment naive, he said. At week 32, PASI-75 response rates were 53% for patients who received apremilast from baseline, and 61% for patients who switched from etanercept to apremilast at week 16.

Based on the results, “I would probably use apremilast more in the moderate [psoriasis] space than in the severe space, but its efficacy does not correlate with baseline disease severity, as far as I know,” said Dr. Reich. Apremilast also beat placebo in analyses of secondary endpoints, including static physician global assessment of clear or almost clear and the Dermatology Quality of Life Index, he added.

Safety analyses showed that the drug was generally well tolerated. Fewer than 4% of patients discontinued treatment because of adverse events, the most common of which were diarrhea, nausea, vomiting, and headache (including tension headache). No new side effects emerged after patients switched from etanercept to apremilast at week 16, he said.

A post hoc analysis found that apremilast was noninferior to etanercept (P > .05) in terms of PASI-75, although the study was not powered to directly compare the two biologics, Dr. Reich noted.

Celgene Corporation makes apremilast and sponsored the study. Dr. Reich reported serving as a speaker for and receiving honoraria from Celgene.

SAN FRANCISCO – More than 80% of psoriasis patients who received ixekizumab achieved a 75% reduction in the Psoriasis Area and Severity Index score and static Physician Global Assessment scores of clear or almost clear skin at 12 weeks, based on the results of a phase III trial.

In addition, 35% of patients who received 80 mg ixekizumab twice monthly for 12 weeks achieved complete resolution of their psoriasis plaques (PASI 100), reported Dr. Kenneth Gordon of Northwestern University in Chicago. “The overall safety profile for ixekizumab was acceptable during both the induction and maintenance phases,” Dr. Gordon said at the annual meeting of the American Academy of Dermatology.

Ixekizumab is a monoclonal antibody that targets interleukin (IL)-17A, a major cytokine in the pathogenesis of psoriasis. Dr. Gordon and his associates conducted a randomized induction and withdrawal trial that compared twice-monthly or monthly treatment of the biologic with placebo among 1,296 patients. During the 12-week induction phase, 431 patients received placebo, 433 received 80 mg ixekizumab every 2 weeks, and 432 received 80 mg ixekizumab every 4 weeks, said Dr. Gordon. He and his associates then rerandomized the responders (based on PASI 75 and static Patient Global Assessment [sPGA] scores) to one of the three protocols, and followed these patients until week 60.

About 80% of patients who received ixekizumab every 2 or 4 weeks achieved sPGA scores of 0 or 1 (clear or almost clear) at 12 weeks, compared with 3% of the placebo group, said Dr. Gordon. Rates of PASI 75 response at 12 weeks were 89% for patients treated twice monthly, 83% for patients treated monthly, and 4% for the placebo group. Rates of PASI 100 were 35%, 33%, and 0%, respectively.

Among initial responders who were rerandomized to monthly ixekizumab, 73% maintained sPGA scores of clear or almost clear at week 60, while 78% maintained or achieved PASI 75, and 52% maintained or achieved PASI 100, said Dr. Gordon. The investigators also found a significant positive linear correlation between PASI response and scores on the Dermatology Quality of Life Index (DLQI), with P values ranging from less than .001 to less than .002, Dr. Gordon reported. “We are seeing that clearance is very important in quality of life,” he added. “More patients reported no itching or other negative impact on quality of life with higher levels of response.”

Serious adverse events at week 12 affected 1.4% of the twice-monthly ixekizumab group, 2.8% of the monthly ixekizumab group, and 1.2% of the placebo group, Dr. Gordon reported. Rates of candidiasis were similar among all three arms. Between weeks 12 and 60, the monthly treatment group had three major adverse cardiac events, but exposure-adjusted rates of adverse events for this group were similar to those during the induction period, he added.

Eli Lilly sponsored the trial. Dr. Gordon reported receiving research funding from Eli Lilly and several other pharmaceutical companies.

SAN FRANCISCO – More than 80% of psoriasis patients who received ixekizumab achieved a 75% reduction in the Psoriasis Area and Severity Index score and static Physician Global Assessment scores of clear or almost clear skin at 12 weeks, based on the results of a phase III trial.

In addition, 35% of patients who received 80 mg ixekizumab twice monthly for 12 weeks achieved complete resolution of their psoriasis plaques (PASI 100), reported Dr. Kenneth Gordon of Northwestern University in Chicago. “The overall safety profile for ixekizumab was acceptable during both the induction and maintenance phases,” Dr. Gordon said at the annual meeting of the American Academy of Dermatology.

Ixekizumab is a monoclonal antibody that targets interleukin (IL)-17A, a major cytokine in the pathogenesis of psoriasis. Dr. Gordon and his associates conducted a randomized induction and withdrawal trial that compared twice-monthly or monthly treatment of the biologic with placebo among 1,296 patients. During the 12-week induction phase, 431 patients received placebo, 433 received 80 mg ixekizumab every 2 weeks, and 432 received 80 mg ixekizumab every 4 weeks, said Dr. Gordon. He and his associates then rerandomized the responders (based on PASI 75 and static Patient Global Assessment [sPGA] scores) to one of the three protocols, and followed these patients until week 60.

About 80% of patients who received ixekizumab every 2 or 4 weeks achieved sPGA scores of 0 or 1 (clear or almost clear) at 12 weeks, compared with 3% of the placebo group, said Dr. Gordon. Rates of PASI 75 response at 12 weeks were 89% for patients treated twice monthly, 83% for patients treated monthly, and 4% for the placebo group. Rates of PASI 100 were 35%, 33%, and 0%, respectively.

Among initial responders who were rerandomized to monthly ixekizumab, 73% maintained sPGA scores of clear or almost clear at week 60, while 78% maintained or achieved PASI 75, and 52% maintained or achieved PASI 100, said Dr. Gordon. The investigators also found a significant positive linear correlation between PASI response and scores on the Dermatology Quality of Life Index (DLQI), with P values ranging from less than .001 to less than .002, Dr. Gordon reported. “We are seeing that clearance is very important in quality of life,” he added. “More patients reported no itching or other negative impact on quality of life with higher levels of response.”

Serious adverse events at week 12 affected 1.4% of the twice-monthly ixekizumab group, 2.8% of the monthly ixekizumab group, and 1.2% of the placebo group, Dr. Gordon reported. Rates of candidiasis were similar among all three arms. Between weeks 12 and 60, the monthly treatment group had three major adverse cardiac events, but exposure-adjusted rates of adverse events for this group were similar to those during the induction period, he added.

Eli Lilly sponsored the trial. Dr. Gordon reported receiving research funding from Eli Lilly and several other pharmaceutical companies.

SAN FRANCISCO – More than 80% of psoriasis patients who received ixekizumab achieved a 75% reduction in the Psoriasis Area and Severity Index score and static Physician Global Assessment scores of clear or almost clear skin at 12 weeks, based on the results of a phase III trial.

In addition, 35% of patients who received 80 mg ixekizumab twice monthly for 12 weeks achieved complete resolution of their psoriasis plaques (PASI 100), reported Dr. Kenneth Gordon of Northwestern University in Chicago. “The overall safety profile for ixekizumab was acceptable during both the induction and maintenance phases,” Dr. Gordon said at the annual meeting of the American Academy of Dermatology.

Ixekizumab is a monoclonal antibody that targets interleukin (IL)-17A, a major cytokine in the pathogenesis of psoriasis. Dr. Gordon and his associates conducted a randomized induction and withdrawal trial that compared twice-monthly or monthly treatment of the biologic with placebo among 1,296 patients. During the 12-week induction phase, 431 patients received placebo, 433 received 80 mg ixekizumab every 2 weeks, and 432 received 80 mg ixekizumab every 4 weeks, said Dr. Gordon. He and his associates then rerandomized the responders (based on PASI 75 and static Patient Global Assessment [sPGA] scores) to one of the three protocols, and followed these patients until week 60.

About 80% of patients who received ixekizumab every 2 or 4 weeks achieved sPGA scores of 0 or 1 (clear or almost clear) at 12 weeks, compared with 3% of the placebo group, said Dr. Gordon. Rates of PASI 75 response at 12 weeks were 89% for patients treated twice monthly, 83% for patients treated monthly, and 4% for the placebo group. Rates of PASI 100 were 35%, 33%, and 0%, respectively.

Among initial responders who were rerandomized to monthly ixekizumab, 73% maintained sPGA scores of clear or almost clear at week 60, while 78% maintained or achieved PASI 75, and 52% maintained or achieved PASI 100, said Dr. Gordon. The investigators also found a significant positive linear correlation between PASI response and scores on the Dermatology Quality of Life Index (DLQI), with P values ranging from less than .001 to less than .002, Dr. Gordon reported. “We are seeing that clearance is very important in quality of life,” he added. “More patients reported no itching or other negative impact on quality of life with higher levels of response.”

Serious adverse events at week 12 affected 1.4% of the twice-monthly ixekizumab group, 2.8% of the monthly ixekizumab group, and 1.2% of the placebo group, Dr. Gordon reported. Rates of candidiasis were similar among all three arms. Between weeks 12 and 60, the monthly treatment group had three major adverse cardiac events, but exposure-adjusted rates of adverse events for this group were similar to those during the induction period, he added.

Eli Lilly sponsored the trial. Dr. Gordon reported receiving research funding from Eli Lilly and several other pharmaceutical companies.

SAN FRANCISCO – An investigational interleukin-23 inhibitor for moderate to severe plaque psoriasis achieved almost twice the PASI 90 response rate of ustekinumab and generated no major safety signals, based on data from randomized trial of 166 patients.

At 12 weeks, 77% of patients treated with 90- or 180-mg doses of BI 655066 were clear or almost clear, compared with 40% of patients treated with weight-based ustekinumab (P < .0001), Dr. Kim A. Papp reported at the annual meeting of the American Academy of Dermatology.

Response to the 180-mg dose of BI 655066 was both early and durable, he noted. “At 4 weeks, we were starting to see these patients do very well. At week 12, almost 80% of patients who received the 180-mg dose achieved PASI 90, and that response was maintained through 24 weeks,” he said. In contrast, the 90-mg dose of BI 65506 was associated with a decline in PASI 90 response after week 16, added Dr. Papp of Probity Medical Research in Waterloo, Ontario.

Past studies have shown that IL-23 plays a key role in psoriasis by mediating the Th17 cell pathway. The BI 655066 agent is a monoclonal antibody that selectively targets IL23p19, while ustekinumab (STELARA) is an IL12/23 antagonist approved for treatment of moderate or severe plaque psoriasis or active psoriatic arthritis. To compare the two biologics, Dr. Papp and his associates randomized 166 patients with moderate or severe plaque psoriasis to subcutaneous treatment with BI 655066 (18 mg at baseline, 90 mg at baseline and week 4, or 180 mg at baseline and week 4) or weight-based ustekinumab (45 or 90 mg at baseline and week 4.) The patient cohorts were demographically similar, had comparable histories of exposure to anti–tumor necrosis factor agents, and their average baseline PASI scores were about 19 to 20, said Dr. Papp.

In all, 90% of patients treated with 90- or 180-mg doses of BI 655066 had achieved static Physicians Global Assessment scores of clear or almost clear at week 12, compared with 67.5% of patients who received ustekinumab, Dr. Papp reported. Furthermore, 46% of BI 655066 patients achieved PASI 100 (complete clearing) at week 12, compared with 17.5% of ustekinumab patients. At week 20, PASI 100 response rates were 62% for the 180-mg group, 53% for the 90-mg group, and 30% for the ustekinumab group, he said.

Rates of adverse events were low and similar for the treatment groups, said Dr. Papp. The most common adverse events were nasopharyngitis and headache, although some patients reported arthralgia and myalgia. The investigators identified no severe or serious treatment-related side effects, nor any sign that adverse effects were more common at higher treatment doses, Dr. Papp said.

Researchers are continuing to assess the safety and efficacy of BI 655066 in an open-label extension trial of patients with plaque psoriasis. That study is using week 48 PASI 90 response as its primary endpoint and will track adverse events for 24 months.

Boehringer Ingelheim funded the study. Dr. Papp disclosed reported relevant relationships with Boehringer Ingelheim and with several other pharmaceutical companies.

SAN FRANCISCO – An investigational interleukin-23 inhibitor for moderate to severe plaque psoriasis achieved almost twice the PASI 90 response rate of ustekinumab and generated no major safety signals, based on data from randomized trial of 166 patients.

At 12 weeks, 77% of patients treated with 90- or 180-mg doses of BI 655066 were clear or almost clear, compared with 40% of patients treated with weight-based ustekinumab (P < .0001), Dr. Kim A. Papp reported at the annual meeting of the American Academy of Dermatology.

Response to the 180-mg dose of BI 655066 was both early and durable, he noted. “At 4 weeks, we were starting to see these patients do very well. At week 12, almost 80% of patients who received the 180-mg dose achieved PASI 90, and that response was maintained through 24 weeks,” he said. In contrast, the 90-mg dose of BI 65506 was associated with a decline in PASI 90 response after week 16, added Dr. Papp of Probity Medical Research in Waterloo, Ontario.

Past studies have shown that IL-23 plays a key role in psoriasis by mediating the Th17 cell pathway. The BI 655066 agent is a monoclonal antibody that selectively targets IL23p19, while ustekinumab (STELARA) is an IL12/23 antagonist approved for treatment of moderate or severe plaque psoriasis or active psoriatic arthritis. To compare the two biologics, Dr. Papp and his associates randomized 166 patients with moderate or severe plaque psoriasis to subcutaneous treatment with BI 655066 (18 mg at baseline, 90 mg at baseline and week 4, or 180 mg at baseline and week 4) or weight-based ustekinumab (45 or 90 mg at baseline and week 4.) The patient cohorts were demographically similar, had comparable histories of exposure to anti–tumor necrosis factor agents, and their average baseline PASI scores were about 19 to 20, said Dr. Papp.

In all, 90% of patients treated with 90- or 180-mg doses of BI 655066 had achieved static Physicians Global Assessment scores of clear or almost clear at week 12, compared with 67.5% of patients who received ustekinumab, Dr. Papp reported. Furthermore, 46% of BI 655066 patients achieved PASI 100 (complete clearing) at week 12, compared with 17.5% of ustekinumab patients. At week 20, PASI 100 response rates were 62% for the 180-mg group, 53% for the 90-mg group, and 30% for the ustekinumab group, he said.

Rates of adverse events were low and similar for the treatment groups, said Dr. Papp. The most common adverse events were nasopharyngitis and headache, although some patients reported arthralgia and myalgia. The investigators identified no severe or serious treatment-related side effects, nor any sign that adverse effects were more common at higher treatment doses, Dr. Papp said.

Researchers are continuing to assess the safety and efficacy of BI 655066 in an open-label extension trial of patients with plaque psoriasis. That study is using week 48 PASI 90 response as its primary endpoint and will track adverse events for 24 months.

Boehringer Ingelheim funded the study. Dr. Papp disclosed reported relevant relationships with Boehringer Ingelheim and with several other pharmaceutical companies.

SAN FRANCISCO – An investigational interleukin-23 inhibitor for moderate to severe plaque psoriasis achieved almost twice the PASI 90 response rate of ustekinumab and generated no major safety signals, based on data from randomized trial of 166 patients.

At 12 weeks, 77% of patients treated with 90- or 180-mg doses of BI 655066 were clear or almost clear, compared with 40% of patients treated with weight-based ustekinumab (P < .0001), Dr. Kim A. Papp reported at the annual meeting of the American Academy of Dermatology.

Response to the 180-mg dose of BI 655066 was both early and durable, he noted. “At 4 weeks, we were starting to see these patients do very well. At week 12, almost 80% of patients who received the 180-mg dose achieved PASI 90, and that response was maintained through 24 weeks,” he said. In contrast, the 90-mg dose of BI 65506 was associated with a decline in PASI 90 response after week 16, added Dr. Papp of Probity Medical Research in Waterloo, Ontario.

Past studies have shown that IL-23 plays a key role in psoriasis by mediating the Th17 cell pathway. The BI 655066 agent is a monoclonal antibody that selectively targets IL23p19, while ustekinumab (STELARA) is an IL12/23 antagonist approved for treatment of moderate or severe plaque psoriasis or active psoriatic arthritis. To compare the two biologics, Dr. Papp and his associates randomized 166 patients with moderate or severe plaque psoriasis to subcutaneous treatment with BI 655066 (18 mg at baseline, 90 mg at baseline and week 4, or 180 mg at baseline and week 4) or weight-based ustekinumab (45 or 90 mg at baseline and week 4.) The patient cohorts were demographically similar, had comparable histories of exposure to anti–tumor necrosis factor agents, and their average baseline PASI scores were about 19 to 20, said Dr. Papp.

In all, 90% of patients treated with 90- or 180-mg doses of BI 655066 had achieved static Physicians Global Assessment scores of clear or almost clear at week 12, compared with 67.5% of patients who received ustekinumab, Dr. Papp reported. Furthermore, 46% of BI 655066 patients achieved PASI 100 (complete clearing) at week 12, compared with 17.5% of ustekinumab patients. At week 20, PASI 100 response rates were 62% for the 180-mg group, 53% for the 90-mg group, and 30% for the ustekinumab group, he said.

Rates of adverse events were low and similar for the treatment groups, said Dr. Papp. The most common adverse events were nasopharyngitis and headache, although some patients reported arthralgia and myalgia. The investigators identified no severe or serious treatment-related side effects, nor any sign that adverse effects were more common at higher treatment doses, Dr. Papp said.

Researchers are continuing to assess the safety and efficacy of BI 655066 in an open-label extension trial of patients with plaque psoriasis. That study is using week 48 PASI 90 response as its primary endpoint and will track adverse events for 24 months.

Boehringer Ingelheim funded the study. Dr. Papp disclosed reported relevant relationships with Boehringer Ingelheim and with several other pharmaceutical companies.

Psoriatic arthritis is associated with higher rates of self-reported angina pectoris, percutaneous coronary intervention, hypertension, obesity, and smoking than are observed in the general population, a large population-based cohort study found.

However, the overall rate of cardiovascular (CV) disease (defined as one or more of angina pectoris, myocardial infarction, cerebrovascular stroke, coronary artery bypass graft, or percutaneous coronary intervention) was 8% in both the 338 patients with psoriatic arthritis (PsA) and the 50,468 controls in the Nord-Trøndelag Health Study. A similar percentage of patients with PsA (13.4%) and controls (11.3%) were deemed to be at very high 10-year risk for a fatal cardiovascular event based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, and the median risk calculated by the algorithm was similar for both groups, Dr. Agnete Malm Gulati of St. Olavs Hospital, Trondheim, Norway, and her coauthors reported. But patients with PsA had significantly higher C-reactive protein levels, body mass index, and diastolic blood pressure, which are not included in the SCORE algorithm.

Patients with PsA had lived with the disease for a mean of 9.3 years, and both patients and controls had a mean age of about 54 years.

The study’s authors said their findings supported previous suggestions that the increased risk of CV disease in psoriatic arthritis was largely a reflection of an increased prevalence of conventional risk factors such as obesity, smoking, and hypertension (Ann. Rheum. Dis. 2015 March 26 [doi:10.1136/annrheumdis-2014-206824]).

“In RA [rheumatoid arthritis], it is shown that atherosclerosis cannot solely be explained by the presence of traditional CV risk factors, and chronic inflammation has also been proposed as being responsible for the enhanced development of atherosclerosis in these patients, [and] this may also be the case for patients with PsA,” the investigators wrote.

The study was supported by Revmafondet i Trondheim, and one author reported financial support from Pfizer. There were no other conflicts of interest declared.

Psoriatic arthritis is associated with higher rates of self-reported angina pectoris, percutaneous coronary intervention, hypertension, obesity, and smoking than are observed in the general population, a large population-based cohort study found.

However, the overall rate of cardiovascular (CV) disease (defined as one or more of angina pectoris, myocardial infarction, cerebrovascular stroke, coronary artery bypass graft, or percutaneous coronary intervention) was 8% in both the 338 patients with psoriatic arthritis (PsA) and the 50,468 controls in the Nord-Trøndelag Health Study. A similar percentage of patients with PsA (13.4%) and controls (11.3%) were deemed to be at very high 10-year risk for a fatal cardiovascular event based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, and the median risk calculated by the algorithm was similar for both groups, Dr. Agnete Malm Gulati of St. Olavs Hospital, Trondheim, Norway, and her coauthors reported. But patients with PsA had significantly higher C-reactive protein levels, body mass index, and diastolic blood pressure, which are not included in the SCORE algorithm.

Patients with PsA had lived with the disease for a mean of 9.3 years, and both patients and controls had a mean age of about 54 years.

The study’s authors said their findings supported previous suggestions that the increased risk of CV disease in psoriatic arthritis was largely a reflection of an increased prevalence of conventional risk factors such as obesity, smoking, and hypertension (Ann. Rheum. Dis. 2015 March 26 [doi:10.1136/annrheumdis-2014-206824]).

“In RA [rheumatoid arthritis], it is shown that atherosclerosis cannot solely be explained by the presence of traditional CV risk factors, and chronic inflammation has also been proposed as being responsible for the enhanced development of atherosclerosis in these patients, [and] this may also be the case for patients with PsA,” the investigators wrote.

The study was supported by Revmafondet i Trondheim, and one author reported financial support from Pfizer. There were no other conflicts of interest declared.

Psoriatic arthritis is associated with higher rates of self-reported angina pectoris, percutaneous coronary intervention, hypertension, obesity, and smoking than are observed in the general population, a large population-based cohort study found.

However, the overall rate of cardiovascular (CV) disease (defined as one or more of angina pectoris, myocardial infarction, cerebrovascular stroke, coronary artery bypass graft, or percutaneous coronary intervention) was 8% in both the 338 patients with psoriatic arthritis (PsA) and the 50,468 controls in the Nord-Trøndelag Health Study. A similar percentage of patients with PsA (13.4%) and controls (11.3%) were deemed to be at very high 10-year risk for a fatal cardiovascular event based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, and the median risk calculated by the algorithm was similar for both groups, Dr. Agnete Malm Gulati of St. Olavs Hospital, Trondheim, Norway, and her coauthors reported. But patients with PsA had significantly higher C-reactive protein levels, body mass index, and diastolic blood pressure, which are not included in the SCORE algorithm.

Patients with PsA had lived with the disease for a mean of 9.3 years, and both patients and controls had a mean age of about 54 years.

The study’s authors said their findings supported previous suggestions that the increased risk of CV disease in psoriatic arthritis was largely a reflection of an increased prevalence of conventional risk factors such as obesity, smoking, and hypertension (Ann. Rheum. Dis. 2015 March 26 [doi:10.1136/annrheumdis-2014-206824]).

“In RA [rheumatoid arthritis], it is shown that atherosclerosis cannot solely be explained by the presence of traditional CV risk factors, and chronic inflammation has also been proposed as being responsible for the enhanced development of atherosclerosis in these patients, [and] this may also be the case for patients with PsA,” the investigators wrote.

The study was supported by Revmafondet i Trondheim, and one author reported financial support from Pfizer. There were no other conflicts of interest declared.

Methotrexate is not associated with an increased risk of pulmonary disease in patients taking it for the treatment of psoriatic arthritis, psoriasis, or inflammatory bowel disease, a meta-analysis has found.

The analysis of results from seven double-blind, randomized, controlled studies, involving a total of 1,640 participants, showed no increased risk of total adverse respiratory events – infectious or noninfectious – or pulmonary deaths in patients taking methotrexate, compared with controls, according to Dr. Richard Conway of the department of rheumatology at Galway (Ireland) University Hospitals and his coauthors.

Methotrexate has previously been implicated as a cause of lung toxicity, and the prevalence of methotrexate-related interstitial lung disease has been reported as high as 11.6% in rheumatoid arthritis, but studies of methotrexate-induced lung disease are confounded by the higher risk of pulmonary infections among patients with rheumatoid arthritis, the authors said (BMJ 2015 [doi:10.1136/bmj.h1269]).

“These findings, coupled with those of a previous study in rheumatoid arthritis, suggest that methotrexate-related lung disease is rare, if it exists at all,” the investigators wrote.

The investigators had no specific source of funding for the study and had no conflicts of interest to declare.

Methotrexate is not associated with an increased risk of pulmonary disease in patients taking it for the treatment of psoriatic arthritis, psoriasis, or inflammatory bowel disease, a meta-analysis has found.

The analysis of results from seven double-blind, randomized, controlled studies, involving a total of 1,640 participants, showed no increased risk of total adverse respiratory events – infectious or noninfectious – or pulmonary deaths in patients taking methotrexate, compared with controls, according to Dr. Richard Conway of the department of rheumatology at Galway (Ireland) University Hospitals and his coauthors.

Methotrexate has previously been implicated as a cause of lung toxicity, and the prevalence of methotrexate-related interstitial lung disease has been reported as high as 11.6% in rheumatoid arthritis, but studies of methotrexate-induced lung disease are confounded by the higher risk of pulmonary infections among patients with rheumatoid arthritis, the authors said (BMJ 2015 [doi:10.1136/bmj.h1269]).

“These findings, coupled with those of a previous study in rheumatoid arthritis, suggest that methotrexate-related lung disease is rare, if it exists at all,” the investigators wrote.

The investigators had no specific source of funding for the study and had no conflicts of interest to declare.

Methotrexate is not associated with an increased risk of pulmonary disease in patients taking it for the treatment of psoriatic arthritis, psoriasis, or inflammatory bowel disease, a meta-analysis has found.

The analysis of results from seven double-blind, randomized, controlled studies, involving a total of 1,640 participants, showed no increased risk of total adverse respiratory events – infectious or noninfectious – or pulmonary deaths in patients taking methotrexate, compared with controls, according to Dr. Richard Conway of the department of rheumatology at Galway (Ireland) University Hospitals and his coauthors.

Methotrexate has previously been implicated as a cause of lung toxicity, and the prevalence of methotrexate-related interstitial lung disease has been reported as high as 11.6% in rheumatoid arthritis, but studies of methotrexate-induced lung disease are confounded by the higher risk of pulmonary infections among patients with rheumatoid arthritis, the authors said (BMJ 2015 [doi:10.1136/bmj.h1269]).

“These findings, coupled with those of a previous study in rheumatoid arthritis, suggest that methotrexate-related lung disease is rare, if it exists at all,” the investigators wrote.

The investigators had no specific source of funding for the study and had no conflicts of interest to declare.

Biosimilars are poised to flood the U.S. pharmaceutical market, bringing biologic therapies within reach of many patients who previously could not pay for them. In a position statement issued last month, the American College of Rheumatology voiced its support for the new agents, but only if they are carefully regulated and tracked – and if prescribing decisions are left up to physicians and patients, not pharmacists or payers.

“As more biologic drugs are used to treat rheumatic diseases, rheumatologists are increasingly concerned about their high cost and patients being unable to afford them,” ACR president William St.Clair said in a written statement. “We agree that less-expensive biologic therapies are needed, and recognize that biosimilars provide an opportunity to reduce treatment costs.”

The ACR position statement follows the U.S. Food and Drug Administration’s approval on March 6 of the first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which is used in cancer treatment and is based on Amgen’s Neupogen (filgrastim). Patents on many other biologics will expire by about 2020, clearing the way for biosimilars used in rheumatology, dermatology, and other fields. Among these, Celltrion’s infliximab biosimilar Remsima (CT-P13) was submitted for FDA approval last year for the treatment of rheumatoid arthritis, Crohn’s disease, and several other conditions. The FDA postponed a March 17 meeting to review Celltrion’s application, stating that it had requested more information from the company.

The ACR has echoed the FDA’s apparent caution regarding biosimilars. Although only the clinically inactive components of biosimilars are allowed to differ from their reference agents, today’s biologics are so molecularly complex that biosimilars need rigorous studies in humans to assess their safety and efficacy, the organization stated. “It is uncertain whether patients will respond to these drugs the same way they would to an original biologic, because biologics are very sensitive to manufacturing changes,” Dr. St.Clair said. “Even minor differences in a biosimilar’s molecular structure, purity, or other chemical properties could change the way a patient responds to the drug.”

For this reason, postmarketing studies in children and adults also will be essential, the ACR stated. Dr. Scott Zashin, a rheumatologist at Presbyterian Hospital, Dallas, and who is also with the University of Texas in Dallas, agreed. “Studies will need to be conducted to determine the benefit and risks,” he said in an interview. “In addition, registries would be needed to help assess long-term safety in larger numbers of patients than is feasible in a clinical trial.”

The ACR also raised concerns about switching patients back and forth between originator biologics and biosimilars, even if the biosimilar met stringent criteria demonstrating its interchangeability with the reference agent. “Experience outside the United States with biosimilar erythropoietin has indicated that a serious adverse reaction due to immunogenicity is a valid and very real concern for biosimilar products,” the ACR stated. “At this time, there are too many unknown variables to presume that repeated switching of biologic drugs would be safe practice.”

Because the FDA has not specified what would be needed to prove that a biologic and its biosimilar are truly interchangeable in the treatment of rheumatic conditions, pharmacists should not be allowed to substitute a biosimilar for a prescribed biologic without written approval from the physician, the ACR stated. But if pharmacists are legally allowed to substitute a biosimilar, they should be required to notify both physicians and patients so that patients can be monitored for adverse effects, the organization added.

Dr. Zashin agreed. “I would pretty much treat the biosimilars as generics, and leave it up to the FDA to decide if they are inferior,” he said. “But there are some generics on the market now (small molecules, not biologics) that I feel are inferior to the brand drug. This would be no different if biosimilars are approved.” For that reason, he would not accept a pharmacist substituting a biosimilar if he prescribed the branded drug, unless the patient preferred and specifically requested the less-expensive product, he said.

Along the same lines, the ACR believes that physicians should be able to designate a prescription as “brand only” if they are concerned about the safety of a biosimilar and that payers should not be able to force patients to switch to a biosimilar if they are already responding well to the biologic. But under current circumstances, “the insurance company would dictate what the patient could receive,” Dr. Zashin cautioned. If the patient refused the biosimilar, “I expect they would penalize the patient and make the brand quite costly.”

Finally, the ACR position statement recommended that biosimilars have distinctive names to easily distinguish them from their reference agents. Otherwise, name confusion could lead to prescribing errors and mistakes during surveillance for adverse events, the organization said.

“We will continue to follow the various issues surrounding the distribution, monitoring, and reimbursement of biosimilars very closely as state and federal policies are proposed that affect our patients and the rheumatologists who serve them,” Dr. St.Clair concluded. “Ensuring patients have easy access to affordable treatment options and rheumatology care continues to be a high priority for us.”

Biosimilars are poised to flood the U.S. pharmaceutical market, bringing biologic therapies within reach of many patients who previously could not pay for them. In a position statement issued last month, the American College of Rheumatology voiced its support for the new agents, but only if they are carefully regulated and tracked – and if prescribing decisions are left up to physicians and patients, not pharmacists or payers.

“As more biologic drugs are used to treat rheumatic diseases, rheumatologists are increasingly concerned about their high cost and patients being unable to afford them,” ACR president William St.Clair said in a written statement. “We agree that less-expensive biologic therapies are needed, and recognize that biosimilars provide an opportunity to reduce treatment costs.”

The ACR position statement follows the U.S. Food and Drug Administration’s approval on March 6 of the first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which is used in cancer treatment and is based on Amgen’s Neupogen (filgrastim). Patents on many other biologics will expire by about 2020, clearing the way for biosimilars used in rheumatology, dermatology, and other fields. Among these, Celltrion’s infliximab biosimilar Remsima (CT-P13) was submitted for FDA approval last year for the treatment of rheumatoid arthritis, Crohn’s disease, and several other conditions. The FDA postponed a March 17 meeting to review Celltrion’s application, stating that it had requested more information from the company.

The ACR has echoed the FDA’s apparent caution regarding biosimilars. Although only the clinically inactive components of biosimilars are allowed to differ from their reference agents, today’s biologics are so molecularly complex that biosimilars need rigorous studies in humans to assess their safety and efficacy, the organization stated. “It is uncertain whether patients will respond to these drugs the same way they would to an original biologic, because biologics are very sensitive to manufacturing changes,” Dr. St.Clair said. “Even minor differences in a biosimilar’s molecular structure, purity, or other chemical properties could change the way a patient responds to the drug.”

For this reason, postmarketing studies in children and adults also will be essential, the ACR stated. Dr. Scott Zashin, a rheumatologist at Presbyterian Hospital, Dallas, and who is also with the University of Texas in Dallas, agreed. “Studies will need to be conducted to determine the benefit and risks,” he said in an interview. “In addition, registries would be needed to help assess long-term safety in larger numbers of patients than is feasible in a clinical trial.”

The ACR also raised concerns about switching patients back and forth between originator biologics and biosimilars, even if the biosimilar met stringent criteria demonstrating its interchangeability with the reference agent. “Experience outside the United States with biosimilar erythropoietin has indicated that a serious adverse reaction due to immunogenicity is a valid and very real concern for biosimilar products,” the ACR stated. “At this time, there are too many unknown variables to presume that repeated switching of biologic drugs would be safe practice.”

Because the FDA has not specified what would be needed to prove that a biologic and its biosimilar are truly interchangeable in the treatment of rheumatic conditions, pharmacists should not be allowed to substitute a biosimilar for a prescribed biologic without written approval from the physician, the ACR stated. But if pharmacists are legally allowed to substitute a biosimilar, they should be required to notify both physicians and patients so that patients can be monitored for adverse effects, the organization added.

Dr. Zashin agreed. “I would pretty much treat the biosimilars as generics, and leave it up to the FDA to decide if they are inferior,” he said. “But there are some generics on the market now (small molecules, not biologics) that I feel are inferior to the brand drug. This would be no different if biosimilars are approved.” For that reason, he would not accept a pharmacist substituting a biosimilar if he prescribed the branded drug, unless the patient preferred and specifically requested the less-expensive product, he said.

Along the same lines, the ACR believes that physicians should be able to designate a prescription as “brand only” if they are concerned about the safety of a biosimilar and that payers should not be able to force patients to switch to a biosimilar if they are already responding well to the biologic. But under current circumstances, “the insurance company would dictate what the patient could receive,” Dr. Zashin cautioned. If the patient refused the biosimilar, “I expect they would penalize the patient and make the brand quite costly.”

Finally, the ACR position statement recommended that biosimilars have distinctive names to easily distinguish them from their reference agents. Otherwise, name confusion could lead to prescribing errors and mistakes during surveillance for adverse events, the organization said.

“We will continue to follow the various issues surrounding the distribution, monitoring, and reimbursement of biosimilars very closely as state and federal policies are proposed that affect our patients and the rheumatologists who serve them,” Dr. St.Clair concluded. “Ensuring patients have easy access to affordable treatment options and rheumatology care continues to be a high priority for us.”

Biosimilars are poised to flood the U.S. pharmaceutical market, bringing biologic therapies within reach of many patients who previously could not pay for them. In a position statement issued last month, the American College of Rheumatology voiced its support for the new agents, but only if they are carefully regulated and tracked – and if prescribing decisions are left up to physicians and patients, not pharmacists or payers.

“As more biologic drugs are used to treat rheumatic diseases, rheumatologists are increasingly concerned about their high cost and patients being unable to afford them,” ACR president William St.Clair said in a written statement. “We agree that less-expensive biologic therapies are needed, and recognize that biosimilars provide an opportunity to reduce treatment costs.”

The ACR position statement follows the U.S. Food and Drug Administration’s approval on March 6 of the first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which is used in cancer treatment and is based on Amgen’s Neupogen (filgrastim). Patents on many other biologics will expire by about 2020, clearing the way for biosimilars used in rheumatology, dermatology, and other fields. Among these, Celltrion’s infliximab biosimilar Remsima (CT-P13) was submitted for FDA approval last year for the treatment of rheumatoid arthritis, Crohn’s disease, and several other conditions. The FDA postponed a March 17 meeting to review Celltrion’s application, stating that it had requested more information from the company.

The ACR has echoed the FDA’s apparent caution regarding biosimilars. Although only the clinically inactive components of biosimilars are allowed to differ from their reference agents, today’s biologics are so molecularly complex that biosimilars need rigorous studies in humans to assess their safety and efficacy, the organization stated. “It is uncertain whether patients will respond to these drugs the same way they would to an original biologic, because biologics are very sensitive to manufacturing changes,” Dr. St.Clair said. “Even minor differences in a biosimilar’s molecular structure, purity, or other chemical properties could change the way a patient responds to the drug.”

For this reason, postmarketing studies in children and adults also will be essential, the ACR stated. Dr. Scott Zashin, a rheumatologist at Presbyterian Hospital, Dallas, and who is also with the University of Texas in Dallas, agreed. “Studies will need to be conducted to determine the benefit and risks,” he said in an interview. “In addition, registries would be needed to help assess long-term safety in larger numbers of patients than is feasible in a clinical trial.”

The ACR also raised concerns about switching patients back and forth between originator biologics and biosimilars, even if the biosimilar met stringent criteria demonstrating its interchangeability with the reference agent. “Experience outside the United States with biosimilar erythropoietin has indicated that a serious adverse reaction due to immunogenicity is a valid and very real concern for biosimilar products,” the ACR stated. “At this time, there are too many unknown variables to presume that repeated switching of biologic drugs would be safe practice.”

Because the FDA has not specified what would be needed to prove that a biologic and its biosimilar are truly interchangeable in the treatment of rheumatic conditions, pharmacists should not be allowed to substitute a biosimilar for a prescribed biologic without written approval from the physician, the ACR stated. But if pharmacists are legally allowed to substitute a biosimilar, they should be required to notify both physicians and patients so that patients can be monitored for adverse effects, the organization added.

Dr. Zashin agreed. “I would pretty much treat the biosimilars as generics, and leave it up to the FDA to decide if they are inferior,” he said. “But there are some generics on the market now (small molecules, not biologics) that I feel are inferior to the brand drug. This would be no different if biosimilars are approved.” For that reason, he would not accept a pharmacist substituting a biosimilar if he prescribed the branded drug, unless the patient preferred and specifically requested the less-expensive product, he said.

Along the same lines, the ACR believes that physicians should be able to designate a prescription as “brand only” if they are concerned about the safety of a biosimilar and that payers should not be able to force patients to switch to a biosimilar if they are already responding well to the biologic. But under current circumstances, “the insurance company would dictate what the patient could receive,” Dr. Zashin cautioned. If the patient refused the biosimilar, “I expect they would penalize the patient and make the brand quite costly.”

Finally, the ACR position statement recommended that biosimilars have distinctive names to easily distinguish them from their reference agents. Otherwise, name confusion could lead to prescribing errors and mistakes during surveillance for adverse events, the organization said.

“We will continue to follow the various issues surrounding the distribution, monitoring, and reimbursement of biosimilars very closely as state and federal policies are proposed that affect our patients and the rheumatologists who serve them,” Dr. St.Clair concluded. “Ensuring patients have easy access to affordable treatment options and rheumatology care continues to be a high priority for us.”

The combination of methotrexate and biologics for the treatment of psoriasis may increase the risk of herpes zoster infection, according to a large, database cohort study published in JAMA Dermatology.

Analysis of medical records for 95,941 patients with psoriasis showed treatment with both biologic medications and methotrexate was associated with a significant 66% increase in the incidence of herpes zoster, compared with a control group, during more than 11 years of follow-up. Episodes of herpes zoster (HZ) occurring in a patient following at least 6 consecutive treatment-free months or in a patient who did not receive any of the listed medications at any time during follow-up were counted as HZ episodes in the control group. The multivariate regression analysis was adjusted for age, sex, psoriasis severity, Charlson comorbidity index, steroid administration per year, and socioeconomic status.

The study found phototherapy, methotrexate alone, cyclosporine, or biologic medications as single agents did not significantly increase the risk, while acitretin therapy was associated with a significant 31% decrease in the incidence of herpes zoster (JAMA Dermatol. 2015 March 22 [doi:10.1001/jamadermatol.2014.4956]).

“Our study results might suggest the need for prophylactic vaccination against VZV [varicella zoster virus] in patients with psoriasis and multiple risk factors for HZ (eg, age, female sex) as part of the preparation for biologic medication treatments in the appropriate clinical setting,” wrote Dr. Guy Shalom of Soroka Medical Center, Beer-Sheva, Israel, and his coauthors.

One author reported consultancies and research grants from a range of pharmaceutical companies. There were no other disclosures.

The combination of methotrexate and biologics for the treatment of psoriasis may increase the risk of herpes zoster infection, according to a large, database cohort study published in JAMA Dermatology.

Analysis of medical records for 95,941 patients with psoriasis showed treatment with both biologic medications and methotrexate was associated with a significant 66% increase in the incidence of herpes zoster, compared with a control group, during more than 11 years of follow-up. Episodes of herpes zoster (HZ) occurring in a patient following at least 6 consecutive treatment-free months or in a patient who did not receive any of the listed medications at any time during follow-up were counted as HZ episodes in the control group. The multivariate regression analysis was adjusted for age, sex, psoriasis severity, Charlson comorbidity index, steroid administration per year, and socioeconomic status.

The study found phototherapy, methotrexate alone, cyclosporine, or biologic medications as single agents did not significantly increase the risk, while acitretin therapy was associated with a significant 31% decrease in the incidence of herpes zoster (JAMA Dermatol. 2015 March 22 [doi:10.1001/jamadermatol.2014.4956]).

“Our study results might suggest the need for prophylactic vaccination against VZV [varicella zoster virus] in patients with psoriasis and multiple risk factors for HZ (eg, age, female sex) as part of the preparation for biologic medication treatments in the appropriate clinical setting,” wrote Dr. Guy Shalom of Soroka Medical Center, Beer-Sheva, Israel, and his coauthors.

One author reported consultancies and research grants from a range of pharmaceutical companies. There were no other disclosures.

The combination of methotrexate and biologics for the treatment of psoriasis may increase the risk of herpes zoster infection, according to a large, database cohort study published in JAMA Dermatology.

Analysis of medical records for 95,941 patients with psoriasis showed treatment with both biologic medications and methotrexate was associated with a significant 66% increase in the incidence of herpes zoster, compared with a control group, during more than 11 years of follow-up. Episodes of herpes zoster (HZ) occurring in a patient following at least 6 consecutive treatment-free months or in a patient who did not receive any of the listed medications at any time during follow-up were counted as HZ episodes in the control group. The multivariate regression analysis was adjusted for age, sex, psoriasis severity, Charlson comorbidity index, steroid administration per year, and socioeconomic status.

The study found phototherapy, methotrexate alone, cyclosporine, or biologic medications as single agents did not significantly increase the risk, while acitretin therapy was associated with a significant 31% decrease in the incidence of herpes zoster (JAMA Dermatol. 2015 March 22 [doi:10.1001/jamadermatol.2014.4956]).

“Our study results might suggest the need for prophylactic vaccination against VZV [varicella zoster virus] in patients with psoriasis and multiple risk factors for HZ (eg, age, female sex) as part of the preparation for biologic medication treatments in the appropriate clinical setting,” wrote Dr. Guy Shalom of Soroka Medical Center, Beer-Sheva, Israel, and his coauthors.

One author reported consultancies and research grants from a range of pharmaceutical companies. There were no other disclosures.

SAN FRANCISCO– Secukinumab met its primary endpoint in a head-to-head trial, achieving 21% more PASI 90 responses than ustekinumab in patients with moderate to severe plaque psoriasis, according to interim, week 16 results from the phase IIIb CLEAR trial.

Patients’ responses to the two biologic agents had diverged by four weeks of treatment, when half the secukinumab group had achieved the secondary endpoint of PASI 75, compared with 20.6% of the ustekinumab group (P < .0001), Dr. Diamant Thaci said at the annual meeting of the American Academy of Dermatology.

“Secukinumab was superior to ustekinumab, even at early time points,” said Dr. Thaci of the Comprehensive Center for Inflammation Medicine at University Medical School Schleswig-Holstein, Lübeck, Germany. “This was very remarkable. Especially remarkable was the early difference for PASI 75.”

The biologic agents also showed similar safety profiles, and secukinumab yielded no new safety signals besides those observed in its pivotal phase III studies. “The most common adverse events were what we have seen in daily practice, including headache, nasopharyngitis, diarrhea, fatigue, and arthralgia,” Dr. Thaci said.

Secukinumab works by binding specifically to the interleukin-17A cytokine, thereby blocking its interaction with its receptor. The 52-week, phase IIIb CLEAR trial, which is underway at 134 sites in 24 countries, is comparing the safety and efficacy of secukinumab and ustekinumab in 679 patients with moderate to severe plaque psoriasis. Patients had baseline PASI scores of at least 12 and at least 10% body surface area involvement, no previous exposure to either biologic agent, and inadequate responses to topical treatments or phototherapy. Researchers randomized the patients to either 300 mg secukinumab given subcutaneously at baseline, at weeks one through four, and every four weeks thereafter, or to ustekinumab, dosed according to label.

The study cohorts resembled one another demographically at baseline. At week 16, 79% of patients given secukinumab had achieved a PASI 90 response, compared with 57.6% of the ustekinumab group (P < .0001). Furthermore, 44.3% of the secukinumab arm had achieved the secondary endpoint of completely clear skin (a PASI 100 response), compared with 28.4% of the ustekinumab group (P < .0001), Dr. Thaci reported.

After an average of 110 to 111 days of treatment, infections and infestations developed in 29.3% of the secukinumab group and 25.3% of ustekinumab group. Three percent of each group developed serious but non-fatal adverse events, with no deaths reported to date.

“Secukinumab treatment – even at early time points – has demonstrated superiority to ustekinumab in clearing the skin of subjects with moderate to severe psoriasis, with a comparable safety profile,” Dr. Thaci concluded. “It is very clear that we will be able to show and to observe that his agent is leading to improved quality of life.”

Dr. Thaci reported receiving research support from Dignity Sciences.

SAN FRANCISCO– Secukinumab met its primary endpoint in a head-to-head trial, achieving 21% more PASI 90 responses than ustekinumab in patients with moderate to severe plaque psoriasis, according to interim, week 16 results from the phase IIIb CLEAR trial.

Patients’ responses to the two biologic agents had diverged by four weeks of treatment, when half the secukinumab group had achieved the secondary endpoint of PASI 75, compared with 20.6% of the ustekinumab group (P < .0001), Dr. Diamant Thaci said at the annual meeting of the American Academy of Dermatology.

“Secukinumab was superior to ustekinumab, even at early time points,” said Dr. Thaci of the Comprehensive Center for Inflammation Medicine at University Medical School Schleswig-Holstein, Lübeck, Germany. “This was very remarkable. Especially remarkable was the early difference for PASI 75.”

The biologic agents also showed similar safety profiles, and secukinumab yielded no new safety signals besides those observed in its pivotal phase III studies. “The most common adverse events were what we have seen in daily practice, including headache, nasopharyngitis, diarrhea, fatigue, and arthralgia,” Dr. Thaci said.

Secukinumab works by binding specifically to the interleukin-17A cytokine, thereby blocking its interaction with its receptor. The 52-week, phase IIIb CLEAR trial, which is underway at 134 sites in 24 countries, is comparing the safety and efficacy of secukinumab and ustekinumab in 679 patients with moderate to severe plaque psoriasis. Patients had baseline PASI scores of at least 12 and at least 10% body surface area involvement, no previous exposure to either biologic agent, and inadequate responses to topical treatments or phototherapy. Researchers randomized the patients to either 300 mg secukinumab given subcutaneously at baseline, at weeks one through four, and every four weeks thereafter, or to ustekinumab, dosed according to label.

The study cohorts resembled one another demographically at baseline. At week 16, 79% of patients given secukinumab had achieved a PASI 90 response, compared with 57.6% of the ustekinumab group (P < .0001). Furthermore, 44.3% of the secukinumab arm had achieved the secondary endpoint of completely clear skin (a PASI 100 response), compared with 28.4% of the ustekinumab group (P < .0001), Dr. Thaci reported.

After an average of 110 to 111 days of treatment, infections and infestations developed in 29.3% of the secukinumab group and 25.3% of ustekinumab group. Three percent of each group developed serious but non-fatal adverse events, with no deaths reported to date.

“Secukinumab treatment – even at early time points – has demonstrated superiority to ustekinumab in clearing the skin of subjects with moderate to severe psoriasis, with a comparable safety profile,” Dr. Thaci concluded. “It is very clear that we will be able to show and to observe that his agent is leading to improved quality of life.”

Dr. Thaci reported receiving research support from Dignity Sciences.

SAN FRANCISCO– Secukinumab met its primary endpoint in a head-to-head trial, achieving 21% more PASI 90 responses than ustekinumab in patients with moderate to severe plaque psoriasis, according to interim, week 16 results from the phase IIIb CLEAR trial.

Patients’ responses to the two biologic agents had diverged by four weeks of treatment, when half the secukinumab group had achieved the secondary endpoint of PASI 75, compared with 20.6% of the ustekinumab group (P < .0001), Dr. Diamant Thaci said at the annual meeting of the American Academy of Dermatology.

“Secukinumab was superior to ustekinumab, even at early time points,” said Dr. Thaci of the Comprehensive Center for Inflammation Medicine at University Medical School Schleswig-Holstein, Lübeck, Germany. “This was very remarkable. Especially remarkable was the early difference for PASI 75.”

The biologic agents also showed similar safety profiles, and secukinumab yielded no new safety signals besides those observed in its pivotal phase III studies. “The most common adverse events were what we have seen in daily practice, including headache, nasopharyngitis, diarrhea, fatigue, and arthralgia,” Dr. Thaci said.

Secukinumab works by binding specifically to the interleukin-17A cytokine, thereby blocking its interaction with its receptor. The 52-week, phase IIIb CLEAR trial, which is underway at 134 sites in 24 countries, is comparing the safety and efficacy of secukinumab and ustekinumab in 679 patients with moderate to severe plaque psoriasis. Patients had baseline PASI scores of at least 12 and at least 10% body surface area involvement, no previous exposure to either biologic agent, and inadequate responses to topical treatments or phototherapy. Researchers randomized the patients to either 300 mg secukinumab given subcutaneously at baseline, at weeks one through four, and every four weeks thereafter, or to ustekinumab, dosed according to label.

The study cohorts resembled one another demographically at baseline. At week 16, 79% of patients given secukinumab had achieved a PASI 90 response, compared with 57.6% of the ustekinumab group (P < .0001). Furthermore, 44.3% of the secukinumab arm had achieved the secondary endpoint of completely clear skin (a PASI 100 response), compared with 28.4% of the ustekinumab group (P < .0001), Dr. Thaci reported.

After an average of 110 to 111 days of treatment, infections and infestations developed in 29.3% of the secukinumab group and 25.3% of ustekinumab group. Three percent of each group developed serious but non-fatal adverse events, with no deaths reported to date.

“Secukinumab treatment – even at early time points – has demonstrated superiority to ustekinumab in clearing the skin of subjects with moderate to severe psoriasis, with a comparable safety profile,” Dr. Thaci concluded. “It is very clear that we will be able to show and to observe that his agent is leading to improved quality of life.”

Dr. Thaci reported receiving research support from Dignity Sciences.

SAN FRANCISCO– Significantly more psoriasis patients who received the investigational biologic agent brodalumab achieved a PASI 100 response compared with those who received ustekinumab, and clinical responses persisted through 52 weeks, according to data from the pivotal phase III AMAGINE-2 trial.

Brodalumab also met its co-primary endpoints (PASI 75 and sPGA 0 or 1) compared with placebo at week 12 when given at doses of either 210 or 140 mg every two weeks, Dr. Mark Lebwohl said at the annual meeting of the American Academy of Dermatology.

But patients maintained the best responses at the higher brodalumab dose, Dr. Lebwohl, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, reported. “Nearly 44% of patients in this group had not a dot of psoriasis left,” he said.

The interleukin-17 (IL-17) receptor and cytokine family play a key role  in the pathogenesis of plaque psoriasis. Brodalumab works by binding the IL-17 receptor, thereby blocking binding by the A, F, and A/F IL-17 cytokines. The AMAGINE-2 trial is the last of a trio of phase III studies to assess brodalumab’s safety and efficacy in patients with moderate to severe plaque psoriasis, Dr. Lebwohl and his associates noted. The findings are consistent with those from earlier trials, they said.

For the study, the researchers enrolled 1,831 patients with moderate to severe plaque psoriasis, of whom 1,776 completed the 12-week induction phase. During induction, patients received either 210 or 140 mg brodalumab, 45 mg of ustekinumab (or 90 mg if they weighed more than 100 kg), or placebo. At week 12, patients were re-randomized to one of the brodalumab or ustekinumab arms.

Fully 44% of patients who received 210 mg brodalumab achieved total clearance of skin disease, or Psoriasis Area Severity Index (PASI) 100 – twice the proportion of the ustekinumab group (22%; P < .001), Dr. Lebwohl said. The 210-mg brodalumab dose also achieved the highest PASI 75 response rate (86%, compared with 70% for ustekinumab, 67% for 140 mg brodalumab, and 8% for placebo), although the adjusted p-value comparing 210 mg brodalumab and ustekinumab did not reach statistical significance (P = .078), he noted. Finally, 79% of patients who received 210 mg brodalumab and 58% of those who received 140 mg brodalumab achieved clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA), compared with only 4% of the placebo group (P < .001), he reported.

Brodalumab’s safety profile during the 12-week induction phase resembled that for previous trials, said Dr. Lebwohl. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia. “But the punch line was Candida,” he said. Candidiasis affected 0.6% of patients in the placebo arm, compared with 1.4% for brodalumab-treated patients at week 12. By week 52, about 4% to 6.5% of treated patients had developed Candida infections.

Similarly small proportions of patients across all arms experienced serious side effects (1% to 2.6%) during the placebo-controlled period, noted Dr. Lebwohl. After adjusting for exposure time, rates of adverse events were similar for all groups, he said. “However, due to disparity in patient-years of exposure between treatment groups, we cannot draw conclusions about potential dose effects,” he added.

Dr. Lebwohl reported receiving research support from Amgen, which is developing brodalumab together with AstraZeneca/MedImmune.

SAN FRANCISCO– Significantly more psoriasis patients who received the investigational biologic agent brodalumab achieved a PASI 100 response compared with those who received ustekinumab, and clinical responses persisted through 52 weeks, according to data from the pivotal phase III AMAGINE-2 trial.

Brodalumab also met its co-primary endpoints (PASI 75 and sPGA 0 or 1) compared with placebo at week 12 when given at doses of either 210 or 140 mg every two weeks, Dr. Mark Lebwohl said at the annual meeting of the American Academy of Dermatology.

But patients maintained the best responses at the higher brodalumab dose, Dr. Lebwohl, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, reported. “Nearly 44% of patients in this group had not a dot of psoriasis left,” he said.

The interleukin-17 (IL-17) receptor and cytokine family play a key role  in the pathogenesis of plaque psoriasis. Brodalumab works by binding the IL-17 receptor, thereby blocking binding by the A, F, and A/F IL-17 cytokines. The AMAGINE-2 trial is the last of a trio of phase III studies to assess brodalumab’s safety and efficacy in patients with moderate to severe plaque psoriasis, Dr. Lebwohl and his associates noted. The findings are consistent with those from earlier trials, they said.

For the study, the researchers enrolled 1,831 patients with moderate to severe plaque psoriasis, of whom 1,776 completed the 12-week induction phase. During induction, patients received either 210 or 140 mg brodalumab, 45 mg of ustekinumab (or 90 mg if they weighed more than 100 kg), or placebo. At week 12, patients were re-randomized to one of the brodalumab or ustekinumab arms.

Fully 44% of patients who received 210 mg brodalumab achieved total clearance of skin disease, or Psoriasis Area Severity Index (PASI) 100 – twice the proportion of the ustekinumab group (22%; P < .001), Dr. Lebwohl said. The 210-mg brodalumab dose also achieved the highest PASI 75 response rate (86%, compared with 70% for ustekinumab, 67% for 140 mg brodalumab, and 8% for placebo), although the adjusted p-value comparing 210 mg brodalumab and ustekinumab did not reach statistical significance (P = .078), he noted. Finally, 79% of patients who received 210 mg brodalumab and 58% of those who received 140 mg brodalumab achieved clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA), compared with only 4% of the placebo group (P < .001), he reported.

Brodalumab’s safety profile during the 12-week induction phase resembled that for previous trials, said Dr. Lebwohl. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia. “But the punch line was Candida,” he said. Candidiasis affected 0.6% of patients in the placebo arm, compared with 1.4% for brodalumab-treated patients at week 12. By week 52, about 4% to 6.5% of treated patients had developed Candida infections.

Similarly small proportions of patients across all arms experienced serious side effects (1% to 2.6%) during the placebo-controlled period, noted Dr. Lebwohl. After adjusting for exposure time, rates of adverse events were similar for all groups, he said. “However, due to disparity in patient-years of exposure between treatment groups, we cannot draw conclusions about potential dose effects,” he added.

Dr. Lebwohl reported receiving research support from Amgen, which is developing brodalumab together with AstraZeneca/MedImmune.

SAN FRANCISCO– Significantly more psoriasis patients who received the investigational biologic agent brodalumab achieved a PASI 100 response compared with those who received ustekinumab, and clinical responses persisted through 52 weeks, according to data from the pivotal phase III AMAGINE-2 trial.

Brodalumab also met its co-primary endpoints (PASI 75 and sPGA 0 or 1) compared with placebo at week 12 when given at doses of either 210 or 140 mg every two weeks, Dr. Mark Lebwohl said at the annual meeting of the American Academy of Dermatology.

But patients maintained the best responses at the higher brodalumab dose, Dr. Lebwohl, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, reported. “Nearly 44% of patients in this group had not a dot of psoriasis left,” he said.

The interleukin-17 (IL-17) receptor and cytokine family play a key role  in the pathogenesis of plaque psoriasis. Brodalumab works by binding the IL-17 receptor, thereby blocking binding by the A, F, and A/F IL-17 cytokines. The AMAGINE-2 trial is the last of a trio of phase III studies to assess brodalumab’s safety and efficacy in patients with moderate to severe plaque psoriasis, Dr. Lebwohl and his associates noted. The findings are consistent with those from earlier trials, they said.

For the study, the researchers enrolled 1,831 patients with moderate to severe plaque psoriasis, of whom 1,776 completed the 12-week induction phase. During induction, patients received either 210 or 140 mg brodalumab, 45 mg of ustekinumab (or 90 mg if they weighed more than 100 kg), or placebo. At week 12, patients were re-randomized to one of the brodalumab or ustekinumab arms.

Fully 44% of patients who received 210 mg brodalumab achieved total clearance of skin disease, or Psoriasis Area Severity Index (PASI) 100 – twice the proportion of the ustekinumab group (22%; P < .001), Dr. Lebwohl said. The 210-mg brodalumab dose also achieved the highest PASI 75 response rate (86%, compared with 70% for ustekinumab, 67% for 140 mg brodalumab, and 8% for placebo), although the adjusted p-value comparing 210 mg brodalumab and ustekinumab did not reach statistical significance (P = .078), he noted. Finally, 79% of patients who received 210 mg brodalumab and 58% of those who received 140 mg brodalumab achieved clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA), compared with only 4% of the placebo group (P < .001), he reported.

Brodalumab’s safety profile during the 12-week induction phase resembled that for previous trials, said Dr. Lebwohl. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia. “But the punch line was Candida,” he said. Candidiasis affected 0.6% of patients in the placebo arm, compared with 1.4% for brodalumab-treated patients at week 12. By week 52, about 4% to 6.5% of treated patients had developed Candida infections.

Similarly small proportions of patients across all arms experienced serious side effects (1% to 2.6%) during the placebo-controlled period, noted Dr. Lebwohl. After adjusting for exposure time, rates of adverse events were similar for all groups, he said. “However, due to disparity in patient-years of exposure between treatment groups, we cannot draw conclusions about potential dose effects,” he added.

Dr. Lebwohl reported receiving research support from Amgen, which is developing brodalumab together with AstraZeneca/MedImmune.