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 language | English (US) |
|---|---|
| Pages (from-to) | 422-434 |
| Number of pages | 13 |
| Journal | New England Journal of Medicine |
| Volume | 375 |
| Issue number | 5 |
| DOIs | |
| State | Published - Aug 4 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
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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U2 - 10.1056/NEJMoa1504370
DO - 10.1056/NEJMoa1504370
M3 - Article
VL - 375
SP - 422
EP - 434
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 5
ER -