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 Sundaram & 3 others Yihua Gu, Dawn M. Carlson, Gregor B E Jemec

Research output: Contribution to journalArticle

152 Citations (Scopus)

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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Hidradenitis Suppurativa
Placebos
Abscess
Adalimumab
Skin Diseases
Multicenter Studies
Fistula
Tumor Necrosis Factor-alpha
Pain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kimball, A. B., Okun, M. M., Williams, D. A., Gottlieb, A. B., Papp, K. A., Zouboulis, C. C., ... 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

Two phase 3 trials of adalimumab for hidradenitis suppurativa. / Kimball, Alexa B.; Okun, Martin M.; Williams, David A.; Gottlieb, Alice B.; Papp, Kim A.; Zouboulis, Christos C.; Armstrong, April W.; Kerdel, Francisco; Gold, Michael H.; Forman, Seth B.; Korman, Neil J.; Giamarellos Bourboulis, Evangelos J.; Crowley, Jeffrey J.; Lynde, Charles; Reguiai, Ziad; Prens, Errol Prospero; Alwawi, Eihab; Mostafa, Nael M.; Pinsky, Brett; Sundaram, Murali; Gu, Yihua; Carlson, Dawn M.; Jemec, Gregor B E.

In: New England Journal of Medicine, Vol. 375, No. 5, 04.08.2016, p. 422-434.

Research output: Contribution to journalArticle

Kimball, AB, Okun, MM, Williams, DA, Gottlieb, AB, Papp, KA, Zouboulis, CC, Armstrong, AW, Kerdel, F, Gold, MH, Forman, SB, Korman, NJ, Giamarellos Bourboulis, EJ, Crowley, JJ, Lynde, C, Reguiai, Z, Prens, EP, Alwawi, E, Mostafa, NM, Pinsky, B, Sundaram, M, Gu, Y, Carlson, DM & Jemec, GBE 2016, 'Two phase 3 trials of adalimumab for hidradenitis suppurativa', New England Journal of Medicine, vol. 375, no. 5, pp. 422-434. https://doi.org/10.1056/NEJMoa1504370
Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. New England Journal of Medicine. 2016 Aug 4;375(5):422-434. https://doi.org/10.1056/NEJMoa1504370
Kimball, Alexa B. ; Okun, Martin M. ; Williams, David A. ; Gottlieb, Alice B. ; Papp, Kim A. ; Zouboulis, Christos C. ; Armstrong, April W. ; Kerdel, Francisco ; Gold, Michael H. ; Forman, Seth B. ; Korman, Neil J. ; Giamarellos Bourboulis, Evangelos J. ; Crowley, Jeffrey J. ; Lynde, Charles ; Reguiai, Ziad ; Prens, Errol Prospero ; Alwawi, Eihab ; Mostafa, Nael M. ; Pinsky, Brett ; Sundaram, Murali ; Gu, Yihua ; Carlson, Dawn M. ; Jemec, Gregor B E. / Two phase 3 trials of adalimumab for hidradenitis suppurativa. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 5. pp. 422-434.
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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 {\'a}, 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.",
author = "Kimball, {Alexa B.} and Okun, {Martin M.} and Williams, {David A.} and Gottlieb, {Alice B.} and Papp, {Kim A.} and Zouboulis, {Christos C.} and Armstrong, {April W.} and Francisco Kerdel and Gold, {Michael H.} and Forman, {Seth B.} and Korman, {Neil J.} and {Giamarellos Bourboulis}, {Evangelos J.} and Crowley, {Jeffrey J.} and Charles Lynde and Ziad Reguiai and Prens, {Errol Prospero} and Eihab Alwawi and Mostafa, {Nael M.} and Brett Pinsky and Murali Sundaram and Yihua Gu and Carlson, {Dawn M.} and Jemec, {Gregor B E}",
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T1 - Two phase 3 trials of adalimumab for hidradenitis suppurativa

AU - Kimball, Alexa B.

AU - Okun, Martin M.

AU - Williams, David A.

AU - Gottlieb, Alice B.

AU - Papp, Kim A.

AU - Zouboulis, Christos C.

AU - Armstrong, April W.

AU - Kerdel, Francisco

AU - Gold, Michael H.

AU - Forman, Seth B.

AU - Korman, Neil J.

AU - Giamarellos Bourboulis, Evangelos J.

AU - Crowley, Jeffrey J.

AU - Lynde, Charles

AU - Reguiai, Ziad

AU - Prens, Errol Prospero

AU - Alwawi, Eihab

AU - Mostafa, Nael M.

AU - Pinsky, Brett

AU - Sundaram, Murali

AU - Gu, Yihua

AU - Carlson, Dawn M.

AU - Jemec, Gregor B E

PY - 2016/8/4

Y1 - 2016/8/4

N2 - 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.

AB - 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.

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