Once-daily oral povorcitinib increased 12-week clinical response rates compared with placebo among adults with moderate to severe hidradenitis suppurativa in two phase 3 randomized controlled trials published in Nature Medicine.
Investigators conducted the identically designed, global, double-blind STOP-HS1 and STOP-HS2 trials at 103 and 99 sites, respectively, across Australia, Canada, Europe, Japan, and the US. Eligible patients had hidradenitis suppurativa (HS) for at least 3 months, at least five abscesses and inflammatory nodules, lesions in at least two anatomic areas, and at least one area classified as Hurley stage II or III. Patients also had an inadequate response, intolerance, or contraindication to at least a 3-month course of an oral antibiotic or biologic.
Participants were randomly assigned 2:2:1:1 to povorcitinib 45 mg, povorcitinib 75 mg, placebo followed by crossover to 45 mg at week 12, or placebo followed by crossover to 75 mg at week 12. Treatment continued through week 54. STOP-HS1 included 608 patients, and STOP-HS2 included 619 patients.
The primary endpoint was Hidradenitis Suppurativa Clinical Response 50 at week 12, defined as at least a 50% reduction from baseline in total abscess and inflammatory nodule count without an increase in abscess or draining tunnel count. Patients who discontinued treatment, received systemic antibiotics for HS, or used prohibited therapies were counted as nonresponders.
In STOP-HS1, the primary response occurred in 40% of patients receiving 45 mg and 41% receiving 75 mg vs 30% receiving placebo. In STOP-HS2, response rates were 42% with either dose vs 29% with placebo. Both doses met the primary endpoint in each trial.
In STOP-HS2, both doses also met the multiplicity-controlled secondary endpoints of Hidradenitis Suppurativa Clinical Response 75, improvement in skin pain, and reduced flare frequency. In STOP-HS1, the key secondary outcomes did not all achieve statistical significance under the prespecified testing hierarchy.
Following placebo crossover, outcomes through week 54 were summarized descriptively. Observed-case Hidradenitis Suppurativa Clinical Response 50 response rates ranged from 57% to 71%, whereas modified nonresponder-imputation estimates ranged from approximately 49% to 60%. No formal statistical comparison was performed between the two povorcitinib doses.
“The clinical responses were rapid and were sustained or further enhanced through week 54,” wrote lead study author Martina L. Porter of the Department of Dermatology at Harvard Medical School and the Beth Israel Deaconess Medical Center, in Boston, Massachusetts, and colleagues.
Through week 54, serious treatment-emergent adverse events were reported in 5% of patients receiving 45 mg and 6% receiving 75 mg. Adverse events led to discontinuation in 8% of each group. Acne occurred in 17% and 20%, respectively, and herpes zoster occurred in 2% of each group. One patient died of an undetermined cause; the investigator considered the event unrelated to treatment.
The investigators noted that interpretation was limited by the 12-week placebo-controlled period, the absence of formal comparisons between the active doses, heterogeneity in underlying disease severity, and the conservative nonresponder-imputation approach.
Disclosures: The study was sponsored by Incyte Corporation, which participated in its design, conduct, data collection, analysis, and manuscript preparation. Full disclosures can be found in the published study.
Source: Nature Medicine
