Refining how we measure as we test: new insights using adalimumab in patients with hidradenitis suppurativa.

Abstract

In the SOLACE study, Gulliver et al.1 evaluate the real-world effectiveness of adalimumab, the first, and, to date, only medication approved for treatment of hidradenitis suppurativa (HS), a debilitating condition characterized by recurrent inflammatory nodules, abscesses, and fistulas. In this large open-label cohort of 138 patients treated with adalimumab, 68.9% achieved HiSCR (a 50% reduction in inflammatory lesion counts) at week 24, higher than the results seen in the PIONEER studies at week 12. Patients with medium to high inflammatory lesion counts (abscesses and inflammatory nodules AN) counts experienced the best response. During the pivotal adalimumab clinical trials, primary endpoints were based on the HiSCR,2 a measure that was analytically derived from the convergence of clinical and patient-reported data in an adalimumab trial. HiSCR does not incorporate improvements in fistulae. Since then, additional tools have emerged including the International HS Severity Score System (IHS4)3 which designates higher weights to draining fistulas and abscesses and, therefore, measures something different than HiSCR. As there is an overlap in the measures, it is not surprising that Gulliver et al. demonstrated that HiSCR responders also had a decrease in IHS4 scores. The best IHS4 responders were those with high AN counts, which seem most responsive to adalimumab. This finding is consistent with work by Frew et al.,4 who did not demonstrate a significant change in the IHS4 category when retrospectively applying the IHS4 to the PIONEER 1 data. Fistulas are an extremely important part of HS, and better treatment options as well as ways to measurement the impact of improvement may still emerge. In the meantime, it seems reasonable to use both scores. It is hard to get HS under control. The first studies with adalimumab showed successful treatment required relatively high doses. Taking into account the open-label design and some population differences, this study confirms that a long duration of treatment may be important to achieve desired clinical effect: the proportion of patients who achieved HiSCR increased from 69% at week 24 to 82% and 75% at week 52 for patients.2 It is difficult to maintain placebo groups past a few months in placebo controlled studies. Given the advances in the field, now is the time to move into an era with more head-to-head comparisons, which will also allow the use of longer primary endpoints. In the meantime, the guidance that it takes time to attain desired effects with adalimumab and other treatments is important for patients and physicians. HS is still hard to treat, but we are continuing to improve both our approach and our results. Dr. Kimball is a consultant and investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Incyte; consultant for Regeneron and Bayer, receives fellowship funding from Janssen and Abbvie; and is on the Board of Directors of Almirall. None.