Two phase 3 trials of adalimumab for hidradenitis suppurativa

Alexa B. Kimball, Martin M. Okun, David A. Williams, Alice B. Gottlieb, Kim A. Papp, Christos C. Zouboulis, April W. Armstrong, Francisco Kerdel, Michael H. Gold, Seth B. Forman, Neil J. Korman, Evangelos J. Giamarellos Bourboulis, Jeffrey J. Crowley, Charles Lynde, Ziad Reguiai, Errol Prospero Prens, Eihab Alwawi, Nael M. Mostafa, Brett Pinsky, Murali SundaramYihua Gu, Dawn M. Carlson, Gregor B E Jemec

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192 Scopus citations

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 á, 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.

Original languageEnglish (US)
Pages (from-to)422-434
Number of pages13
JournalNew England Journal of Medicine
Volume375
Issue number5
DOIs
StatePublished - Aug 4 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

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Kimball, A. B., Okun, M. M., Williams, D. A., Gottlieb, A. B., Papp, K. A., Zouboulis, C. C., Armstrong, A. W., Kerdel, F., Gold, M. H., Forman, S. B., Korman, N. J., Giamarellos Bourboulis, E. J., Crowley, J. J., Lynde, C., Reguiai, Z., Prens, E. P., Alwawi, E., Mostafa, N. M., Pinsky, B., ... Jemec, G. B. E. (2016). Two phase 3 trials of adalimumab for hidradenitis suppurativa. New England Journal of Medicine, 375(5), 422-434. https://doi.org/10.1056/NEJMoa1504370