Alexa B. Kimball

BackgroundGuselkumab, an interleukin-23 blocker, was superior to adalimumab in treating moderate to severe psoriasis in a phase II trial.ObjectivesWe sought to compare efficacy and safety of guselkumab with adalimumab and placebo in patients with psoriasis treated for 1 year.MethodsPatients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 329); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20, then every 8 weeks; n = 174); or adalimumab (80 mg week 0, 40 mg week 1, then 40 mg every 2 weeks through week 47; n = 334). Physician-reported outcomes (Investigator Global Assessment, Psoriasis Area and Severity Index [PASI]), patient-reported outcomes (Dermatology Life Quality Index, Psoriasis Symptoms and Signs Diary), and safety were evaluated through week 48.ResultsGuselkumab was superior (P < .001) to placebo at week 16 (85.1% vs 6.9% [Investigator Global Assessment score of 0/1 (cleared/minimal)] and 73.3% vs 2.9% [90% or greater improvement in PASI score from baseline (PASI 90)]). Guselkumab was also superior (P < .001) to adalimumab for Investigator Global Assessment 0/1 and PASI 90 at week 16 (85.1% vs 65.9% and 73.3% vs 49.7%), week 24 (84.2% vs 61.7% and 80.2% vs 53.0%), and week 48 (80.5% vs 55.4% and 76.3% vs 47.9%). Furthermore, guselkumab significantly improved patient-reported outcomes through week 48. Adverse event rates were comparable between treatments.LimitationsAnalyses were limited to 48 weeks.ConclusionsGuselkumab demonstrated superior efficacy compared with adalimumab and was well tolerated in patients with psoriasis through 1 year. Guselkumab, an interleukin-23 blocker, was superior to adalimumab in treating moderate to severe psoriasis in a phase II trial. We sought to compare efficacy and safety of guselkumab with adalimumab and placebo in patients with psoriasis treated for 1 year. Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 329); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20, then every 8 weeks; n = 174); or adalimumab (80 mg week 0, 40 mg week 1, then 40 mg every 2 weeks through week 47; n = 334). Physician-reported outcomes (Investigator Global Assessment, Psoriasis Area and Severity Index [PASI]), patient-reported outcomes (Dermatology Life Quality Index, Psoriasis Symptoms and Signs Diary), and safety were evaluated through week 48. Guselkumab was superior (P < .001) to placebo at week 16 (85.1% vs 6.9% [Investigator Global Assessment score of 0/1 (cleared/minimal)] and 73.3% vs 2.9% [90% or greater improvement in PASI score from baseline (PASI 90)]). Guselkumab was also superior (P < .001) to adalimumab for Investigator Global Assessment 0/1 and PASI 90 at week 16 (85.1% vs 65.9% and 73.3% vs 49.7%), week 24 (84.2% vs 61.7% and 80.2% vs 53.0%), and week 48 (80.5% vs 55.4% and 76.3% vs 47.9%). Furthermore, guselkumab significantly improved patient-reported outcomes through week 48. Adverse event rates were comparable between treatments. Analyses were limited to 48 weeks. Guselkumab demonstrated superior efficacy compared with adalimumab and was well tolerated in patients with psoriasis through 1 year.

BACKGROUND: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. METHODS: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100). RESULTS: At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab. CONCLUSIONS: Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).

BACKGROUND: Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa. METHODS: PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12. RESULTS: We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences. CONCLUSIONS: Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).