Background Safety of biologics is important when treating patients with psoriasis. Objective We sought to determine the safety of ixekizumab in psoriasis. Methods Integrated safety data are presented ...from a 12-week induction period, a 12- to 60-week maintenance period, and from all ixekizumab-treated patients from 7 clinical trials. Exposure-adjusted incidence rates (IRs) per 100 patient-years are reported. Results Overall, 4209 patients received ixekizumab (total exposure: 6480 patient-years). During the induction period, the IRs of patients experiencing 1 or more treatment-emergent adverse event (AE) were 251 and 236 among ixekizumab- and etanercept-treated patients, respectively, and for serious AEs was 8.3 in both groups. During maintenance, for ixekizumab, the IRs of treatment-emergent AEs and serious AEs were 100.4 and 7.8, respectively. Among all ixekizumab-treated patients from 7 trials, the IR of Candida infections was 2.5. The IRs of treatment-emergent AEs of special interest (including serious infections, malignancies, major adverse cardiovascular events) were comparable for ixekizumab and etanercept during the induction period. Limitations Additional long-term data are required. Conclusion Ixekizumab had an acceptable safety profile with no unexpected safety findings during ixekizumab maintenance in psoriasis.
Background New psoriasis therapies have increased the ability to achieve skin clearance. However, insufficient evidence exists on the impact of total skin clearance from the patient perspective. ...Objective We sought to determine if complete skin clearance is clinically meaningful compared with treatment responses without clearance. Methods Pooled data from 3 phase-III trials were used to compare results for patients with complete skin clearance (Psoriasis Area and Severity Index PASI 100 or static Physician Global Assessment score 0) with patients without complete skin clearance (PASI 75 to <100 or static Physician Global Assessment score 1) based on Psoriasis Symptom Inventory and Dermatology Life Quality Index. Results Percentages of patients with Psoriasis Symptom Inventory score 0 were 45% for those achieving PASI 100 and 8% for PASI 75 to <100 ( P < .001). Respective percentages with Dermatology Life Quality Index score 0/1 were 80% and 55% ( P < .001). PASI 100 resulted in incremental improvement over PASI 90 to <100 (incremental differences of 28% for Psoriasis Symptom Inventory score 0 and 18% for Dermatology Life Quality Index score 0). Similar results were observed for static Physician Global Assessment scores 0 versus 1. Conclusions Complete skin clearance represents a clinically meaningful end point and outcome for patients, reflected in experiences of no psoriasis symptoms and no impairment on health-related quality of life.
Background ABP 501 is a biosimilar of adalimumab. Objective We sought to compare the efficacy and safety of ABP 501 with adalimumab. Methods This 52-week, double-blind study randomized patients with ...moderate to severe psoriasis to ABP 501 or adalimumab. At week 16, those with 50% or more improvement in Psoriasis Area and Severity Index score from baseline on ABP 501 continued the same treatment, whereas adalimumab-treated patients were rerandomized to adalimumab or ABP 501. Clinical similarity in Psoriasis Area and Severity Index percent improvement from baseline to week 16 (primary end point) was established if the point estimate of treatment difference and its 2-sided 95% confidence interval between groups was within equivalence margin of ±15. Patients, including those undergoing a single transition at week 16, were evaluated for safety and immunogenicity. Results Psoriasis Area and Severity Index percent improvement at week 16 was 80.9 for ABP 501 and 83.1 for adalimumab (least-square mean difference −2.18 95% confidence interval −7.39 to 3.02). Adverse events (67.2% 117/174 vs 63.6% 110/173) and antidrug antibody incidence (55.2% 96/174 vs 63.6% 110/173) for ABP 501 vs adalimumab were similar. Safety, including immunogenicity, was similar among groups after single transition (week 20). Limitations The 52-week data are not reported here. Conclusions ABP 501 was shown to be clinically similar to adalimumab. Safety and immunogenicity were not impacted immediately after single transition (adalimumab to ABP 501).
Background Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. ...Objective We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis. Methods Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib. Results Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years. Limitations There was relatively short follow-up time for patients who had MACEs. Conclusions While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low.
Background Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor, a key proinflammatory cytokine involved in the pathogenesis of psoriasis. Objective We sought to evaluate ...clinical efficacy and safety of adalimumab for moderate to severe psoriasis and investigate continuous versus interrupted therapy. Methods We conducted a 52-week, multicenter study of 1212 patients randomized to receive adalimumab (40 mg) or placebo every other week for the first 15 weeks. At least 75% improvement in the Psoriasis Area and Severity Index (PASI) score was the criterion for advancement through this multiphase study. Results At week 16, 71% (578 of 814) of adalimumab- and 7% (26 of 398) of placebo-treated patients achieved greater than or equal to 75% improvement in the PASI score. During weeks 33 to 52, the percentage of patients rerandomized to placebo who lost adequate response (defined as <50% improvement in the PASI response relative to baseline and at least a 6-point increase in PASI score from week 33) was 28% compared with 5% of patients treated continuously with adalimumab. Limitations Lack of an active comparator and evaluation of maintenance of response beyond week 52 are limitations. Conclusion Adalimumab is efficacious and well-tolerated in the treatment of chronic plaque psoriasis. Trial Registration Clinical trials.gov. NCT00237887.
There have been several articles and reports in recent months about comorbidities and risks that affect psoriasis patients in addition to their underlying disease. This piece reviews the current ...literature and begins to address what should be done with this new information by updating the clinician about what health screening tests, preventative exams, and referrals should be considered in this population.
Background Comparing effectiveness of biologics in real-world settings will help inform treatment decisions. Objectives We sought to compare therapeutic responses among patients initiating ...infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness. Results Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha(-α) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab odds ratio {OR} 0.396, P < .0001, adalimumab OR 0.686, P = .0012, etanercept OR 0.554, P = .0003 at 6 months and infliximab OR 0.449, P = .0040 at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months. Limitations Treatment selection bias and limited data for doing adjustments are limitations. Conclusions In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months.
Background Novel therapies are needed for difficult-to-treat populations of patients with psoriasis. Objective We sought to assess the efficacy and safety of the interleukin-17 Receptor A inhibitor ...brodalumab in patients with psoriasis with or without a self-reported history of psoriatic arthritis (PsA) and with or without a history of biologic use. Methods Subset analyses of a phase II, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis were performed. Improvement from baseline in Psoriasis Area and Severity Index score of 75%, 90%, and 100% at week 12; static Physician Global Assessment (0/1) score; Dermatology Life Quality Index response; and Psoriasis Symptom Inventory response were evaluated within subgroups. Results Efficacy and quality-of-life measures were generally similar between subgroups of patients with or without a history of PsA and with or without a history of biologic use across brodalumab doses and were significantly higher among patients who received brodalumab 140 mg every 2 weeks or 210 mg every 2 weeks versus placebo. Limitations Differences between subgroups were not compared statistically, PsA was self-reported, only skin involvement/symptoms were reported, and reasons for discontinuation of prior biologic were not captured. Conclusion Brodalumab is efficacious in patients with psoriasis with or without a history of PsA or biologic use.
Abstract The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the association of various ...cardiometabolic comorbidities with psoriasis. In November 2013, a workshop was held in Boston, Mass. By assembling a panel of global dermatology, immunology, and cardiovascular experts, the objective was to better define the current status of the science that explains the association of psoriasis with various cardiometabolic-related comorbidities. The International Psoriasis Council has played a historical role in associating psoriasis with various comorbidities by integrating multidisciplinary expertise to advance the scientific and clinical knowledge through publications and clinical trials. This report synthesizes the current understanding of psoriasis with various cardiometabolic risk factors by exploring the potential shared pathogenic mechanisms and genetic connectivity.
Background Strategies for transitioning patients with psoriasis from suboptimal therapy have not been delineated. Objective We sought to determine the efficacy and safety of transitioning to ...adalimumab for the treatment of psoriasis in patients with suboptimal response to prior therapy with etanercept, methotrexate (MTX), or narrowband (NB)-ultraviolet (UV)B phototherapy. Methods In this 16-week, open-label, phase IIIb trial, patients with chronic plaque psoriasis discontinued suboptimal therapy between 11 and 17 days (etanercept) or between 4 and 10 days (MTX and NB-UVB) before initiating adalimumab (80 mg at week 0, then 40 mg every other week from week 1). The primary end point was the percentage of patients achieving a Physician Global Assessment of “clear” or “minimal” at week 16. Results At week 16, Physician Global Assessment of “clear” or “minimal” was achieved by 52% of all enrolled patients (79 of 152) and 49%, 61%, and 48% in the etanercept, MTX, and NB-UVB subgroups, respectively. Four patients (2.6%) experienced at least 125% worsening of Psoriasis Area and Severity Index score relative to screening value at any study visit. The adalimumab safety profile was consistent with results from other psoriasis clinical trials. Limitations This study is limited by its relatively short 16-week duration, small patient enrollment, and open-label design. Conclusion Patients who had a suboptimal response to etanercept, MTX, or NB-UVB phototherapy experienced a similar, approximately 50% likelihood of achieving a clinically relevant response to adalimumab. Immediate transition to adalimumab from prior suboptimal therapy, with no dosage tapering or overlap, had a low risk of psoriasis flare.
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