Calibrating biologic treatment of HS to the response patterns to biologics

Treatment for hidradenitis suppurativa (HS) has changed significantly with approval of biologics for moderate to severe cases of the disease. So far, the FDA has approved Humira (adalimumab) and its biosimilars, Costenyx (secukinumab) and Bimzelx (bimekizumab) for HS. But as corresponding author Axel P. Vallini, M.D., Ph.D., and his co-authors note in their paper published last week in JAMA Dermatology, the biologics are far from a cure-all. Between 40% and 60% of the patients enrolled in their pivotal trials did not achieve a Hidradenitis Suppurativa Clinical Response at induction, and the drugs stopped working for a sizable proportion of patients. Villani and his colleagues, citing a 2023 study published in the Lancet, report that 23% of patients prescribed Cosentyx stopped responding to the drug after a year. They described two patterns of cases when biologics fall short as treatments for HS: an end-of-dose effect (EODE) when the disease starts to recur in the days before the next injection, suggesting “pharmacokinetic insufficiency,” or persistent inflammation through the dosing interval. In real-world practice, clinicians increase the intensity of treatment with biologics when they see the EODE pattern and will add antibiotics to treatment when they see persistent inflammation.

Villani and his colleagues, most of whom are, like him, at Hospices Civils de Lyon, a health system in Lyon, France, set out to assess those two approaches in a more systematic way in a retrospective cohort study. A total of 107 patients with HS were assessed for “response-pattern-guided biologic optimization. They selected 52 with EODE for dose intensification (weekly treatments with Humira or its biosimilars, for example, or biweekly treatments with Costenyx), while 50 without EODE were treated with oral antibiotics. The remaining five were treated with both strategies.

After some exclusions and some no-shows, the French researchers end up with 102 patients, and three to five months after their biologic therapy was optimized, their average International Hidradenitis Suppurativa Severity Score System (IHS4) score — a standardized scale for measuring the response to HS treatment — was 3.9, down from 7.0 at baseline.

The study’s primary outcome was a reduction of at least 3 points in IHS4 score. Just over half (53.8%, 50 of 93) of the evaluable patients reached it.

Villani and his colleagues also reported a collection of positive results on secondary outcomes. Among 84 patients, average pain scores on a 0-to-10 scale slid from 6.2 to 4.2, and 36 (42.9%) moved to a lower pain category. The share of patients having more than four flares a month dropped from 38.2% to 18.6%, and just over half (51%, 52 of 102 patients) moved to a lower flare-frequency category. Flares also got shorter, with 41 (47.7%) of the 86 evaluable patients on this end point indicating that they had shorter flares than at baseline. Overall, 65 of 100 patients (65.0%) said their condition had improved.

Villani and his colleagues said in the discussion section of the paper that theirs was, to the best of their knowledge, “the largest real-world description of a response-pattern-guided optimization strategy in patients with HS. Although nearly half of the patients did not reach the primary outcome, the researchers described the results as showing “clinically meaningful improvement across all prespecified outcomes.” The results show, they said, “support a personalized approach to biologic optimization in HS” and also point to using EODE as a “candidate phenotyping to guide optimization strategy selection.”

Still, this was a single-center, retrospective study. And the researchers note the lack of a control arm. These findings are far from the final word. Adequately powered prospective trials are needed to confirm their findings, wrote Villani and his co-authors, and to refine the algorithm they used to assign patients to the safest, most efficacious response-pattern-guided treatment.