Orismilast may improve hidradenitis suppurativa with dose-dependent tolerability

Key takeaways:

• 11 of 20 patients discontinued due to adverse events.
• Of the nine patients that completed treatment, 67% saw a 50% reduction in abscesses and nodules.

Orismilast may improve mild to severe hidradenitis suppurativa; however, further studies are needed to confirm patient tolerability in this indication, according to a study.

“Phosphodiesterase-4 (PDE4) inhibition is promising for the treatment of chronic inflammatory diseases,” Camilla G. Frederiksen, MD, of the department of dermatology at Zealand University Hospital in Denmark, and colleagues wrote. “Inhibition of PDE4B/D subtypes drives the anti-inflammatory effects of PDE4 inhibitors in immune cells and impact the production of pro-inflammatory cytokines.”

To evaluate the efficacy of PDE4 inhibition in patients with hidradenitis suppurativa (HS), the investigators conducted a phase 2a trial evaluating orismilast, an oral PDE4 inhibitor.

In this single-arm, single-center, open-label trial, 20 adult patients (mean age, 40.9 years; 13 women) with mild to severe HS were treated with orismilast for 16 weeks. Initially, the investigators planned a 2-week titration schedule with a target dose of 40 mg twice a day; however, this rapid dose escalation caused unacceptable tolerability as shown through numerous gastrointestinal adverse events and discontinuations.

With the 14 patients that remained after early discontinuations, the investigators revamped the schedule to allow for a more individualized approach with slower titration and a lower target dosage. Ultimately, 11 patients discontinued the trial early and nine completed the 16 weeks of treatment with most taking a dose lower than the twice-daily 40 mg initial dose (n = 6).

Among the patients that completed treatment, the investigators saw a reduction in abscesses and nodules (AN-count) from 5.3 (95% CI, 1.3-9.4) to 3.8 (95% CI, –2.5 to 10) by week 16, equating to a 33.1% reduction in AN-count. On the other hand, those who discontinued treatment saw a 12% reduction in AN-count from 4.6 (95% CI, 2.1-7) to 4.3 (95% CI, 1.3-7.3) by week 16.

Also, six (67%) patients that completed treatment achieved HS Clinical Response, defined as a 50% reduction in AN-count, vs. three (27%) of those that discontinued treatment.

A total of 197 adverse events were reported, 80% of which were adverse drug reactions. Four serious adverse events occurred including anaphylactic shock after initiating penicillin for a urinary tract infection, a urinary tract infection that led to urosepsis and new onset of ulcerative colitis. However, none of these serious adverse events were considered related to orismilast.

“The results of this small trial suggest that PDE4B/D-inhibition with orismilast may lead to clinical improvements in HS,” the authors wrote. “However, larger trials at the most tolerable dose ranges are warranted based on the results of this exploratory trial.”