Background Available psoriasis surveys offer valuable information about psoriasis and psoriatic arthritis (PsA), but are limited by methodology or enrollment requirements. Objective To further the ...understanding of the unmet needs of psoriasis and PsA patients. Methods This was a large, multinational, population-based survey of psoriasis and/or PsA patients in North America and Europe. Patients were selected by list-assisted random digit dialing and did not have to currently be under the care of a health care provider, a patient organization member, or receiving treatment; 139,948 households were screened and 3426 patients completed the survey. Results The prevalence of psoriasis/PsA ranged from 1.4% to 3.3%; 79% had psoriasis alone and 21% had PsA. When rating disease severity at its worst, 27% (psoriasis) and 53% (PsA ± psoriasis) of patients rated it as severe. Psoriasis patients indicated that their most bothersome signs or symptoms were itching (43%), scales (23%), and flaking (20%). Of psoriasis patients, 45% had not seen a physician in a year; >80% of psoriasis patients with ≥4 palms body surface area and 59% of PsA patients were receiving no treatment or topical treatment only. Of patients who had received oral or biologic therapy, 57% and 45%, respectively, discontinued therapy, most often for safety/tolerability reasons and a lack/loss of efficacy. Limitations The survey lacked a control group, did not account for ethnic and health care system differences across countries, and was limited by factors associated with any patient survey, including accurate recall and interpretation of questions. Conclusions Several identified unmet needs warrant additional attention and action, including improved severity assessment, PsA screening, patient awareness, and treatment options.
Background Phase II data suggested that guselkumab, an anti-interleukin-23 monoclonal antibody, was efficacious in psoriasis. Objective We sought to assess efficacy and safety of guselkumab in ...moderate to severe psoriasis versus placebo and adalimumab, including interrupted treatment and switching adalimumab nonresponders to guselkumab. Methods Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 496); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20; n = 248); or adalimumab (80 mg week 0, then 40 mg week 1, and every 2 weeks through week 23; n = 248). At week 28, guselkumab 90% or greater improvement in Psoriasis Area and Severity Index (PASI) score from baseline (PASI 90) responders were rerandomized to guselkumab or placebo with guselkumab after loss of response. Placebo→guselkumab responders and adalimumab responders received placebo, then guselkumab after loss of response. Nonresponders received guselkumab. Results At week 16, more patients receiving guselkumab achieved an Investigator Global Assessment (IGA) score 0/1 (cleared/minimal) (84.1% vs 8.5%) and PASI 90 (70.0% vs 2.4%) versus placebo (coprimary end points). Guselkumab was superior to adalimumab at week 16 (IGA score 0/1, 75% or greater improvement in PASI score from baseline, and PASI 90) and week 24 (IGA score 0/1 and 0, PASI 90, 100% improvement in PASI score from baseline) ( P < .001). From weeks 28 to 48, better persistence of response was observed in guselkumab maintenance versus withdrawal groups ( P < .001). Of adalimumab nonresponders who switched to guselkumab, 66.1% achieved PASI 90 at week 48. Guselkumab improved patient-reported outcomes. Adverse events were comparable among groups. Limitations One-year follow-up limits retreatment data. Conclusions Guselkumab is a highly effective, well-tolerated, maintenance therapy, including in adalimumab nonresponders.
Background Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis. Objective ...To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks. Methods Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study. Results Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% P < .0001); PASI 100 responses were 46% versus 36% ( P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% ( P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index DLQI, EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab ( P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable. Limitations There was no placebo arm. Conclusion In this head-to-head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile.
Background Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study). ...Objective We sought to directly compare efficacy and safety of secukinumab versus ustekinumab. Methods In this 52-week, double-blind study ( NCT02074982 ), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per label. Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at week 16. Results Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at week 16 ( P < .0001). The 100% improvement from baseline PASI score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%) ( P < .0001). The 75% or more improvement from baseline PASI score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) ( P < .0001). Percentage of subjects with the Dermatology Life Quality Index score 0/1 (week 16) was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%) ( P < .0001). The safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies. Limitations The study was not placebo-controlled and of short-term duration. Conclusions Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks.
Background Apremilast works intracellularly to regulate inflammatory mediators. Objective ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque ...psoriasis. Methods This phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ2 test; continuous end points used analysis of covariance. Results In all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was −88% to −81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period. Limitations Data were limited to 52 weeks and may not generalize to nonplaque psoriasis. Conclusions Apremilast was effective in moderate to severe plaque psoriasis.
Background Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe plaque psoriasis. Objective We reviewed safety ...data from the secukinumab psoriasis phase II/III program. Methods Data were pooled from 10 phase II/III secukinumab psoriasis studies. Results Analysis included 3993 subjects; 3430 received secukinumab, representing 2725 subject-years (SYs) of exposure. Over 52 weeks, for secukinumab 300 mg, 150 mg, and etanercept, respectively, exposure-adjusted incidence rates (IRs) per 100 SYs were comparable across treatments for total adverse events (AEs; 236.1, 239.9, and 243.4, respectively); infections (91.1, 85.3, and 93.7, respectively); serious AEs (7.4, 6.8, and 7.0, respectively); serious infections (1.4, 1.1, and 1.4, respectively); malignant or unspecified tumors (0.77, 0.97, and 0.68, respectively); and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34, respectively). AEs were not dose-related except for nonserious, mild/moderate, skin/mucosal candidiasis (IRs 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively). Limitations There was a limited number of patients in comparator groups and the exposure to placebo was short. Conclusion Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque 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 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 A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate ...whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. Objectives We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. Methods In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients’ diaries. The safety and tolerability of omalizumab were also assessed. Results Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo ( P = .0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. Conclusions The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.
Background Inflammatory bowel disease (IBD) occurs more frequently in patients with psoriasis. The 2 diseases have significant genetic overlap, but the pathogenesis underlying their co-occurrence is ...unknown. Objective We sought to report adjudicated IBD cases (Crohn's disease CD and ulcerative colitis UC) in patients exposed to ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. Methods Adverse events (AEs) integrated from 7 randomized controlled and uncontrolled trials were analyzed for the controlled induction period, controlled maintenance period, and all ixekizumab-treated patients. Suspected IBD cases were reviewed by blinded external experts using internationally recognized criteria (Registre Epidemiologique des Maladies de l'Appareil Digestif registry). Results In all, 4209 patients (6480 patient-exposure years) were exposed to ixekizumab. Suspected CD (N = 12) or UC (N = 17) AEs were reported; 19 were adjudicated as definite/probable IBD (CD, N = 7, incidence rate = 1.1/1000 patient-exposure years; UC, N = 12, incidence rate = 1.9/1000 patient-exposure years). Among these, 3 occurred during induction (CD, N = 1; UC, N = 2) and 7 during maintenance (CD, N = 4; UC, N = 3). Twelve of 16 patients with reported IBD history have not had an IBD treatment-emergent AE/serious AE to date. Limitations Clinical review (adjudication) was not prespecified. AE data collected post-hoc may have been limited by length of time from occurrence. Conclusion From an integrated database of 7 ixekizumab psoriasis trials, CD and UC cases were uncommon (<1%).
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