Alexa B Kimball1, Martin M Okun1, David A Williams1, Alice B Gottlieb1, Kim A Papp1, Christos C Zouboulis1, April W Armstrong1, Francisco Kerdel1, Michael H Gold1, Seth B Forman1, Neil J Korman1, Evangelos J Giamarellos-Bourboulis1, Jeffrey J Crowley1, Charles Lynde1, Ziad Reguiai1, Errol-Prospero Prens1, Eihab Alwawi1, Nael M Mostafa1, Brett Pinsky1, Murali Sundaram1, Yihua Gu1, Dawn M Carlson1, Gregor B E Jemec1. 1. From Harvard Medical School and Massachusetts General Hospital (A.B.K.) and Tufts Medical Center (A.B.G.) - all in Boston; AbbVie, North Chicago, IL (M.M.O., D.A.W., E.A., N.M.M., B.P., M.S., Y.G., D.M.C.); Probity Medical Research and K Papp Clinical Research, Waterloo, ON (K.A.P.), and the Lynde Centre for Dermatology and Probity Medical Research, Markham, ON (C.L.) - both in Canada; the Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany (C.C.Z.); University of Southern California, Los Angeles (A.W.A.), and Bakersfield Dermatology, Bakersfield (J.J.C.) - both in California; Florida Academic Dermatology Centers, Miami (F.K.), and Forward Clinical Trials, Tampa (S.B.F.) - both in Florida; Tennessee Clinical Research Center, Nashville (M.H.G.); University Hospitals Case Medical Center, Cleveland (N.J.K.); 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens (E.J.G.-B.); CHU de Reims, Hôpital Robert Debré, Service de Dermatologie, Reims, France (Z.R.); Erasmus University Medical Center, Rotterdam, the Netherlands (E.-P.P.); and the Department of Dermatology, Roskilde Hospital, and Health Sciences Faculty, University of Copenhagen, Copenhagen (G.B.E.J.).
Abstract
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 adalimumabfor 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.).
RCT Entities:
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.).
Authors: Eran Shavit; Afsaneh Alavi; Falk G Bechara; Richard G Bennett; Marc Bourcier; Ricardo Cibotti; Steven Daveluy; John W Frew; Amit Garg; Iltefat Hamzavi; Lauren K Hoffman; Jenny Hsaio; Joslyn Sciacca Kirby; Hadar Lev-Tov; Erin Martinez; Robert Micheletti; Haley B Naik; Aude Nassif; Cynthia Nicholson; Angie Parks-Miller; Zarine Patel; Vincent Piguet; Mayur Ramesh; Barry Resnik; Christopher Sayed; Gregory Schultz; Aamir Siddiqui; Jerry Tan; Ximena Wortsman; Michelle A Lowes Journal: Exp Dermatol Date: 2019-01 Impact factor: 3.960