Hidradenitis suppurativa programs are built around a composite lesion-count responder endpoint. The way regulators defined and accepted that endpoint shapes trial design, sample size and the labeling a sponsor can expect. Teams planning HS development, or preparing a label negotiation, also need to know whether patient-reported outcomes such as skin pain and quality of life are likely to appear in the prescribing information in each region, because this affects both endpoint hierarchy and commercial positioning.
The analysis below compares the originator biologics with HS indications in the US and EU. It covers how HiSCR50 and HiSCR75 were defined, which primary timepoints were used, and which pain and patient-reported outcome results FDA labels and EMA SmPCs each included. It also covers where adalimumab biosimilars fit relative to the reference-product labeling.
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Hidradenitis suppurativa approvals at FDA and EMA: how HiSCR50/HiSCR75 were defined and which pain and PRO claims reached the label
Three biologics hold hidradenitis suppurativa (HS) indications in both the US and the EU: adalimumab (Humira), secukinumab (Cosentyx) and bimekizumab (Bimzelx). US labels for adalimumab biosimilars (for example Hyrimoz, Hadlima, Amjevita) and EU adalimumab biosimilars (for example Amgevita, Imraldi, Hyrimoz) also carry HiSCR-based HS text 131136138717976. That text follows the reference products, so this article covers the three originator programs.
All three programs used the same clinician-assessed lesion-count responder endpoint, the Hidradenitis Suppurativa Clinical Response (HiSCR). The two agencies treated patient-reported pain and quality-of-life data very differently in labeling. EU SmPCs report skin-pain responder results for all three products. US labels carry no numerical pain or PRO results for any of them.
Key takeaways
- HiSCR50 is the same across agencies and products. It requires at least a 50% reduction from baseline in total abscess plus inflammatory nodule (AN) count, with no increase in abscesses and no increase in draining fistulas/tunnels 88817112175.
- HiSCR75 keeps the same no-worsening safeguards and raises the AN threshold to 75% 17112175. Only bimekizumab has labeled HiSCR75 results (US and EU) 106111.
- Primary timepoint: Week 12 for adalimumab 8849. Week 16 for secukinumab and bimekizumab 5819106111.
- Pain: EU SmPCs report skin-pain responder rates for adalimumab (NRS30) 7, secukinumab (NRS30, pooled) 2124 and bimekizumab (HSSDD worst skin pain, at least a 3-point reduction) 111. US labels describe the pain assessment without results (Humira), omit it entirely (Cosentyx), or, for Bimzelx, state a descriptive at-least-3-point worst-skin-pain (lesion pain) improvement versus placebo without numerical rates 19521334.
- Quality of life: DLQI appears in all three EU SmPCs. Bimekizumab's SmPC gives numerical data, while adalimumab and secukinumab have qualitative statements only 117721. No DLQI claim appears in any of the three US labels 9634106.
Approved HS indications
| Product | FDA indication (US PI) | EMA indication (EU SmPC) |
|---|---|---|
| Humira (adalimumab) | "Moderate to severe hidradenitis suppurativa in patients 12 years of age and older" (label dated December 23, 2025) 163 | "Active moderate to severe hidradenitis suppurativa (acne inversa) in adults and adolescents from 12 years of age with an inadequate response to conventional systemic HS therapy" 51 |
| Cosentyx (secukinumab) | "Moderate to severe hidradenitis suppurativa (HS) in adults and pediatric patients 12 years of age and older" (section 1.6 updated 3/2026) 202 | "Active moderate to severe hidradenitis suppurativa (acne inversa) in adults with an inadequate response to conventional systemic HS therapy" 17 |
| Bimzelx (bimekizumab) | "Adults with moderate to severe hidradenitis suppurativa" (revised 11/2024) 151152 | "Active moderate to severe hidradenitis suppurativa (acne inversa) in adults with an inadequate response to conventional systemic HS therapy" 121 |
The EU indications consistently restrict use to patients with an inadequate response to conventional systemic HS therapy. The US indications carry no such line-of-therapy restriction. Humira's EU indication, unlike Cosentyx and Bimzelx, also includes adolescents from 12 years of age. The SmPC states there are no Humira clinical trials in adolescent HS; that dose was set by pharmacokinetic modelling. For adalimumab, CHMP also required that claims about preventing worsening of abscesses and fistulae be removed from the indication wording. CHMP cited the mechanism of action and the characteristics of the trial population 13.
How response was defined
HiSCR50 (the primary endpoint in every program)
| Program | Pivotal trials | Primary timepoint | Definition wording in label/EPAR |
|---|---|---|---|
| Adalimumab | HS Study I / PIONEER I (M11-313), HS Study II / PIONEER II (M11-810) 8849 | Week 12 | At least 50% reduction in total AN count with no increase in abscess count and no increase in draining fistula count relative to baseline 1958 |
| Secukinumab | HS Trial 1 / SUNSHINE (M2301, NCT03713619), HS Trial 2 / SUNRISE (M2302, NCT03713632) 581922 | Week 16 | US PI: at least a 50% decrease in AN count with "no increase in the number of abscesses and/or in the number of draining fistulae" 60. EU SmPC: no increase in abscesses and no increase in draining fistulae 17 |
| Bimekizumab | HS-1 / BE HEARD I (HS0003), HS-2 / BE HEARD II (HS0004) 106111 | Week 16 | At least 50% reduction in total AN count, no increase in abscesses and no increase in draining tunnels 106112 |
The Cosentyx US PI uses "and/or" between the two no-worsening criteria 60. The EU SmPC and FDA's clinical pharmacology text state both criteria conjunctively 17159210. Bimekizumab documents use "draining tunnels" where the older adalimumab and secukinumab documents use "draining fistulas" 106112.
HiSCR75
HiSCR75 applies the same no-increase conditions for abscesses and draining fistulas/tunnels, with a 75% AN-count reduction threshold. The secukinumab SmPC 17, the bimekizumab EPAR 112 and FDA's bimekizumab review 175 all define it this way. HiSCR75 was a ranked secondary endpoint for bimekizumab, not a primary endpoint 111130. The Bimzelx US PI reports HiSCR75 rates but does not define HiSCR75 106.
How regulators judged HiSCR as an endpoint
- Adalimumab (EMA). CHMP/SAWP were concerned that the originally proposed AN50 endpoint would not capture disease progression. This led to the composite HiSCR, which adds the no-worsening criteria 5. The EPAR concluded that HiSCR was adequately validated for its intended use. Its assessment covered construct validity, predictive validity and responsiveness, with correlations to Hurley stage, modified Sartorius score, pain VAS, HS-PGA and DLQI 5. The 50% cut-off was accepted because patients with less than 30% AN reduction showed no meaningful DLQI or pain improvement 5. Inter- and intra-rater reliability of lesion counts was considered adequate (ICCs 0.68 to 0.92), although abscess counts had the lowest ICCs 5.
- Adalimumab (FDA). HiSCR was the primary endpoint agreed under a Special Protocol Assessment. FDA found Humira superior to placebo in both Phase 3 trials 150.
- Secukinumab (EMA). CHMP considered HiSCR clinically aligned with HS because it captures abscesses, inflammatory nodules and draining fistulas. CHMP also noted its prior use for adalimumab and its endorsement in scientific advice 212.
- Bimekizumab (EMA). CHMP judged the Week 16 differences versus placebo on both HiSCR50 and the "more stringent" HiSCR75 to be clinically relevant 129.
Efficacy results on the label
| Product / trial | Endpoint | Placebo | Active arm(s) | Source |
|---|---|---|---|---|
| Humira HS-I | HiSCR, Wk 12 | 26% (40/154) | 42% (64/153), 40 mg weekly | US PI 88; EU 26.0% vs 41.8% 8 |
| Humira HS-II | HiSCR, Wk 12 | 28% (45/163) | 59% (96/163) | US PI 88; EU 27.6% vs 58.9% 8 |
| Cosentyx HS Trial 1 | HiSCR50, Wk 16 | 29.4% | 41.3% Q4W; 44.5% Q2W (significant) | US PI 60 |
| Cosentyx HS Trial 2 | HiSCR50, Wk 16 | 26.1% | 42.5% Q4W (significant); 38.3% Q2W (significant) | US PI 60 |
| Cosentyx SUNSHINE / SUNRISE | HiSCR50, Wk 16 | 33.7% / 31.2% | Q2W 45.0% / 42.3%; Q4W 41.8% / 46.1% | EPAR 192131 |
| Bimzelx HS-1 | HiSCR50 / HiSCR75, Wk 16 | 29% / 18% | 48% / 33%, 320 mg Q2W | US PI 106 |
| Bimzelx HS-2 | HiSCR50 / HiSCR75, Wk 16 | 32% / 16% | 52% / 36%, 320 mg Q2W | US PI 106 |
| Bimzelx BE HEARD I | HiSCR50 / HiSCR75, Wk 16 | 28.7% / 18.4% | Q4W 45.3% / 24.7%; Q2W 47.8% / 33.4% | EU 111 |
| Bimzelx BE HEARD II | HiSCR50 / HiSCR75, Wk 16 | 32.2% / 15.6% | Q4W 53.8% / 33.7%; Q2W 52.0% / 35.7% | EU 111 |
The secukinumab response rates in the US PI and the EU documents differ slightly for the same trials 601921. Anyone drafting comparative or promotional materials should use the figures from the relevant jurisdiction's label. The US Bimzelx PI presents only the Q2W arm 106. The EU presentation includes both Q2W and Q4W. HiSCR75 in BE HEARD I was met for Q2W but not for Q4W, and in BE HEARD II it was met for both regimens 127.
Pain and patient-reported outcome claims: what reached the label
Summary matrix
| Claim | Humira US | Humira EU | Cosentyx US | Cosentyx EU | Bimzelx US | Bimzelx EU |
|---|---|---|---|---|---|---|
| Skin pain responder result | Method described, no results 195 | NRS30 results by trial 7 | Not described 34 | NRS30 pooled results 2124 | Descriptive ≥3-point worst skin pain (lesion pain) claim versus placebo; no numerical rates 213 | HSSDD worst skin pain, at least 3-point response, results by trial 111 |
| DLQI | No 96 | Qualitative statement (both trials) 7 | No 34 | Qualitative statement 2124 | No 106 | Mean change results 117 |
| Other PROs | None 96 | TSQM, SF-36 PCS (qualitative) 7 | None 34 | None with results 202124 | None 106 | None beyond pain/DLQI 111117 |
| Flare | Flare after withdrawal, Period B (22%) 195 | Reduced flare risk, weeks 0 to 12 7 | Not described 34 | Flare rates by trial 2021 | Not described 106 | Not in SmPC 5.1 111 |
Adalimumab
Endpoint. The ranked secondary NRS30 endpoint was based on the Patient's Global Assessment of Skin Pain "at worst." It required at least a 30% and at least a 1-unit reduction from baseline at Week 12, in patients with a baseline NRS of 3 or higher 11146147. The item is a 0 to 10 scale covering worst HS-related skin pain over the prior 24 hours 1472.
EU SmPC. The SmPC table reports NRS30 responses of 24.8% vs 27.9% in HS-I (not marked significant) and 20.7% vs 45.7% in HS-II (p<0.001), placebo vs Humira weekly 7. The SmPC also states that DLQI and TSQM improved more than with placebo in both trials, and that the SF-36 physical component summary improved in HS-I. It reports a significantly reduced risk of flare during the first 12 weeks 7. CHMP noted that the ranked secondary endpoints, including NRS30, had been discussed in scientific advice 5. CHMP concluded that the DLQI and TSQM data showed an adalimumab effect 13.
US PI. The label says only that skin pain was assessed on an 11-point NRS in patients with a baseline score of 3 or more. It reports no results 195. FDA's review states that the skin-pain results were excluded from labeling because they did not replicate across the two Phase 3 trials 145146. None of the ranked secondary endpoints, NRS30 included, reached statistical significance in M11-313 150. The US PI does include a flare finding from the randomized withdrawal period. Flare, defined as at least a 25% increase in AN count with a minimum of 2 additional lesions, occurred in 22 of 100 subjects (22%) withdrawn from Humira after the primary timepoint 195.
Secukinumab
Endpoint. NRS30 was defined more strictly than for adalimumab. It required at least a 30% and at least a 2-unit reduction in the Patient's Global Assessment of Skin Pain (at worst) at Week 16, in patients with a baseline NRS of 3 or higher 1763207.
EU SmPC. NRS30 was a secondary endpoint analysed on pooled SUNSHINE/SUNRISE data 20. Responses were 23.0% with placebo (58/251), 33.5% with Q4W (84/252) and 36.6% with Q2W (97/266). Only the Q2W result was statistically significant 2124. The SmPC states qualitatively that DLQI improved at Week 16 2124. The assessment report defines a DLQI response as a decrease of more than 5 points 30. Flare (at least a 25% increase in AN count plus at least 2 AN) is reported by trial. Q2W was significant in SUNSHINE (15.4% vs 29.0%) and Q4W was significant in SUNRISE (15.6% vs 27.0%) 172021. The HS Symptom Diary, EQ-5D-3L, PGI-S, PGI-C and WPAI-SHP were exploratory, and their results do not appear in SmPC section 5.1 30. CHMP described the pain and flare results as consistent with HiSCR and supportive of a clinically relevant effect 29.
US PI. The HS section reports only HiSCR50. It includes no skin-pain, DLQI or flare results 34. FDA's exposure-response review lists NRS30 and flare as secondary endpoints and DLQI as a major exploratory endpoint 182.
Bimekizumab
Endpoint. The program replaced NRS30 with a responder threshold anchored to the Hidradenitis Suppurativa Symptom Daily Diary (HSSDD). The HSSDD worst-skin-pain item is a daily, electronic, 24-hour-recall, 0 to 10 NRS 154. At End-of-Phase 2, FDA advised measuring pain "at its worst" rather than using a 30% pain-reduction endpoint. FDA also recommended anchor-based analyses to derive meaningful-change thresholds 176. FDA's COA review found that the item's content validity was generally supported. It placed meaningful within-patient improvement at roughly 2.4 to 4.8 points and described a 3 to 4 point reduction as clinically meaningful 173154.
EU SmPC. Section 5.1 reports the HSSDD worst-skin-pain response, defined as a reduction of at least 3 points in patients with a baseline score of 3 or higher. Rates were 15.0% placebo, 22.1% Q4W and 32.3% Q2W in BE HEARD I, and 10.9%, 28.6% and 31.8% in BE HEARD II 111. DLQI mean change (0 to 30 scale) is also reported. BE HEARD I showed -2.9 with placebo, -5.4 with Q4W and -5.0 with Q2W. BE HEARD II showed -3.2, -4.5 and -4.6 117. The SmPC states that the DLQI improvements were sustained through Week 48 117. Pain and DLQI sat within the hierarchical secondary testing strategy 114.
US PI. HS-specific skin pain response is named as a secondary endpoint on a 0 to 10 NRS 106. The current US PI reports no numerical rates, but it states that BIMZELX was associated with an improvement in worst skin pain (lesion pain), based on a reduction of at least 3 points on a 0 to 10 NRS, compared with placebo at Week 16 213. The FDA reviews explain why numerical rates were not included. In HS0003, Q2W was not statistically superior to placebo on the at-least-3-point pain response, which ended formal testing of the remaining secondary endpoints 157. In HS0004, the flare endpoint failed ahead of the pain endpoints in the hierarchy (p ≥0.497), so statistical claims could not be made for pain 157. The COA reviewer left it to the Division to decide whether a descriptive pain claim was acceptable, and recommended "pain" or "lesion pain" rather than "skin pain" 154173. The current PI uses both: "worst skin pain (lesion pain)" 213. HiSQOL results were expressly excluded from labeling because they were exploratory with no formal hypothesis testing 154156. FDA had earlier raised content-validity and multibarreled-item concerns about DLQI 176.
Why the labels diverge
The evidence points to a consistent pattern.
- US labeling depends on multiplicity-controlled, replicated results. Humira's pain data were dropped because the result did not replicate across trials 145146. Bimzelx's numerical pain claim was blocked by breaks in the testing hierarchy, although a descriptive at-least-3-point worst-skin-pain (lesion pain) statement still appears in the US PI 157213.
- FDA reviews the instrument and the threshold themselves. FDA steered the bimekizumab program away from NRS30 toward an anchor-based "worst pain" threshold 176. It also raised concerns about DLQI's content validity 176.
- EU SmPCs describe secondary and PRO findings more freely. The SmPCs report pain responder rates even where only one trial or one dose arm reached significance 721111. DLQI and other quality-of-life measures appear in qualitative or descriptive form 721117.
For sponsors planning HS programs, the precedents suggest the following. A US pain claim needs a pre-specified worst-pain responder threshold, supported by anchor-based meaningful-change work. That endpoint should also sit early enough in the testing hierarchy to survive both pivotal trials. The same data may reach an EU SmPC under a more descriptive standard.