Efficacy Results Using a Novel Hidradenitis Suppurativa Endpoint, Hiscr (Hidradenitis Suppurativa Clinical Response), From The Placebo-Controlled Phase of a Phase 2 Adalimumab Study

Abstract

Hidradenitis suppurativa (HS) is a painful, chronic inflammatory skin follicular disease with manifestations that include recurrent inflamed nodules, abscesses, and fistulas. Several scores have been proposed as outcome measures. We report efficacy results using the novel endpoint Hidradenitis Suppurativa Clinical Response (HiSCR; ≥50% reduction from baseline in total abscess and inflammatory nodule [AN] count, with no observed increase in either abscess or draining fistula counts) from the 16-week, double-blind, placebo-controlled phase of a 52-week adalimumab (ADA) study. Moderate to severe HS patients were randomized 1:1:1 (intent to treat population [ITT]) to placebo (n=51), ADA 40mg every other week, 80mg at Week 0 (W0) (eow, n=52), or ADA 40mg every week, 160mg at W0, 80mg at W2 (ew, n=51). For patients with baseline AN count ≥3 and draining fistula count ≤20 (mITT population), the following retrospective evaluations are reported for W12 and W16: percentage of patients achieving HS-Physician Global Assessment (HS-PGA)−based Clinical Response (non-responder imputation [NRI]); percentage of patients achieving HiSCR; percentage of patients achieving 50%, 75%, 100% reduction in total AN count (AN50, AN75, AN100) relative to baseline (NRI), and percent change from baseline in AN count (last observation carried forward). In the mITT population at W12 and W16, respectively, HS-PGA−based Clinical Response rates (%) for placebo/eow/ew groups were 4.7/6.7/25.0 (p<0.05 placebo vs ew) and 2.3/6.7/20.5 (p<0.05 placebo vs ew). HiSCR response rates (%) at W12 and W16, respectively, for placebo/eow/ew groups were 16.3/35.6/59.1 (p<0.05 placebo vs ew and placebo vs ewo) and 25.6/33.3/54.5 (p<0.05 placebo vs ew). For placebo/eow/ew groups, percentages (%) of patients achieving specified percent reduction in AN counts at W12 were 32.6/42.2/63.6 (AN50); 20.9/28.9/43.2 (AN75); 4.7/6.7/22.7 (AN100) and at W16, 34.9/48.9/56.8 (AN50); 27.9/24.4/40.9 (AN75); 2.3/8.9/20.5 (AN100). For placebo/eow/ew groups, mean percent (%) reduction from baseline in AN count at W12 was 12.2/32.3/60.3, and at Wk16, 19.8/38.8/59.7. ADA efficacy was demonstrated in moderate to severe HS patients. Differences for ADA ew vs placebo in HS-PGA−based Clinical Response and HiSCR at W12 and W16 were statistically significant. Percent improvement in AN counts was greater after ADA ew treatment. HiSCR appeared more responsive to change and better able to discriminate improvement in eow-treated patients than HS-PGA−based Clinical Response and may be a useful new tool to assess HS therapy efficacy in clinical practice and research trials.