Review calls for combining outcome measures for hidradenitis suppurativa treatment

The clinical trial endpoint most commonly used to measure hidradenitis suppurativa treatment response excludes a significant proportion of trial patients with milder or improving disease and doesn't fully capture how the disease affects their lives, according to a review published in the Journal of the European Academy of Dermatology and Venereology.

Hidradenitis suppurativa is a chronic inflammatory skin disease characterized by painful nodules, abscesses and draining tunnels that affects an estimated 0.4% to 1% of the general population, the study authors explained. Diagnosis is routinely delayed by more than 10 years, and 63.7% of patients see a physician five or more times before getting one, according to the Global Survey of Impact and Healthcare Needs (VOICE) project cited in the review. Three biologics are now approved for moderate-to-severe disease: adalimumab, secukinumab and bimekizumab, with additional small molecules, including JAK inhibitors, in development.

The expanding treatment landscape has raised the stakes for how trials and clinicians define success. The Hidradenitis Suppurativa Clinical Response (HiSCR) endpoint, developed for the trials that led to adalimumab's approval, remains the field's most used primary endpoint. However, the review’s authors note that HiSCR requires a count of at least three abscesses and inflammatory nodules — a threshold milder or improving cases don't meet. It also treats draining tunnels only as a “non-worsening” variable rather than crediting improvement in them, and it ignores body surface area entirely. Those gaps contribute to a median placebo response rate of 31% across 11 phase 2 and 3 trials, the authors found.

What IHS4-55 adds that HiSCR doesn't

The International Hidradenitis Suppurativa Severity Score System (IHS4) closes two of those gaps: it weights draining tunnels four times as heavily as nodules, and it has no minimum lesion requirement, making it usable in milder cases HiSCR can't assess. Germany's S2k treatment guideline now recommends IHS4 as its standard classification tool, and the 2025 European S2k guidelines endorse it alongside HiSCR.

The dichotomous version of the IHS4, the IHS4-55, defined as at least a 55% reduction in IHS4 score, has been adopted as a co-primary endpoint in the BE HEARD I and II bimekizumab trials. In the SUNSHINE and SUNRISE secukinumab trials, 43.4% of patients on a twice-monthly dose and 39.5% on a monthly dose achieved IHS4-55 by week 16, compared with 31.5% on placebo.

How patient-reported tools are evolving

On the patient-reported side, the Dermatology Life Quality Index (DLQI) remains the most-used quality-of-life instrument in hidradenitis suppurativa studies, with a minimal clinically important difference of four points or more. But it isn't disease-specific and misses symptoms such as odor and drainage.

The Hidradenitis Suppurativa Quality of Life (HiSQOL) tool was built specifically for the disease and now has a validated minimal clinically important difference of 20 to 21 points, based on pooled data from the BE HEARD I and II trials. A pain numeric rating scale, with a minimal important difference of one point, rounds out the core outcome domains recommended by the HiSTORIC research consortium.

Structural damage still goes undercounted

Even with those tools, the review's authors argue that hidradenitis suppurativa outcome measurements still miss irreversible tissue damage. Ultrasound-based staging has found 44.7% to 58.5% of patients are understaged by standard clinical exams because subclinical tunnels go undetected, according to research cited by the authors. Ultra-high-frequency ultrasound reclassified 69.7% of patients who scored as having “mild” disease by IHS4 up to “moderate.”

And a 52-week adalimumab monitoring study found that while inflammation and swelling improved with treatment, fibrosis in unhealed tunnels didn't budge and sometimes worsened, meaning patients can reach inflammatory remission by trial standards while retaining significant structural damage. There is also no formal consensus definition of remission, optimal disease control or progression in hidradenitis suppurativa, but a “treat-to-target” framework is under development to address that gap, the review authors noted.

The VOICE project, which surveyed 1,828 patients across 27 institutions in 14 countries, found that 45.9% of patients were dissatisfied with their medical treatment and 34.6% were dissatisfied with procedural treatment, underscoring a disconnect between clinician-reported scores and how patients experience the disease.

“Evidence that biologics modify inflammation without reversing established fibrosis and tunnelling underscores the need to distinguish inflammatory from structural endpoints, which current outcome instruments do not yet encode,” the review's authors wrote in the journal.