The oral JAK1 inhibitor povorcitinib elicits clinical response in the subpopulation of hidradenitis suppurativa (HS) patients who had prior treatment with anti-TNF, according to pooled 24-week data from the phase III STOP-HS trials.
At week 12, the primary endpoint of at least 50-percent skin clearance (HiSCR 50*) was achieved in 39 percent of patients in the 45-mg povorcitinib arm, 36.3 percent in the 75-mg arm, and 21.4 percent in the placebo arm. [AAD 2026, poster 75195]
Povorcitinib was also associated with higher rates of high threshold responses, including HiSCR 75 (19.5 percent with the 45-mg dose and 22.1 percent with the 75-mg dose vs 4.1 percent with placebo) and HiSCR 90 (10.2 percent and 13.3 percent vs 3.1 percent, respectively). A ≥3-point reduction in Skin Pain NRS was reported by 19.6 percent and 18.2 percent of patients in the povorcitinib 45- and 75-mg arms, respectively, as opposed to 7.5 percent in the placebo arm.
Continued improvements were seen at week 24 in patients who were initially randomized to povorcitinib and those who crossed over to povorcitinib after 12 weeks, reported first study author Dr Christopher Sayed from the University of North Carolina School of Medicine, Chapel Hill, North Carolina, US.
The rates of HiSCR 50 were 48.3 percent in the 45-mg povorcitinib arm, 44 percent in the 75-mg arm, 48.6 percent in the placebo-to-45-mg-crossover arm, and 63.4 percent in the placebo-to-75-mg-crossover arm. HiSCR 75 rates were 33.7 percent, 27.4 percent, 34.3 percent, and 34.1 percent; while HiSCR 90 rates were 20.2 percent, 14.3 percent, 14.3 percent, and 24.4 percent, respectively.
The percentage of patients who reported a ≥3-point decrease in Skin Pain NRS at week 24 was 33.3 percent in the 45-mg povorcitinib arm, 34.4 percent in the 75-mg arm, 36.4 percent in the placebo-to-45-mg-crossover arm, and 39.4 percent in the placebo-to-75-mg-crossover arm.
“Safety and tolerability were favourable at both povorcitinib doses, with a very low frequency of laboratory abnormalities over 24 weeks,” Sayed noted.
Treatment-emergent adverse events (TEAEs) occurred in 35.6 percent of patients in the 45-mg povorcitinib arm, 46.4 percent in the 75-mg arm, 27.5 percent in the placebo-to-45-mg-crossover arm, and 34.8 percent in the placebo-to-75-mg-crossover arm. The rates of serious TEAEs were 7.6 percent, 7.1 percent, 2.5 percent, and 4.3 percent, respectively. TEAEs led to treatment discontinuation in 8.5 percent, 4.5 percent, 2.5 percent, and 6.5 percent of patients in the respective treatment arms. No cases of fatal TEAEs were documented.
Among AEs of special interest, two cases of malignancies, two cases of serious infections, and one case of herpes zoster were documented.
“Overall, povorcitinib is a promising treatment option for anti-TNF–experienced patients, who have recalcitrant HS and may have more severe disease,” Sayed said.
STOP-HS1 and STOP-HS2 were identically designed international phase III trials involving a total of 1,227 adult patients with moderate-to-severe HS (STOP-HS1, n=608; STOP-HS2, n=619). These patients were randomly assigned to receive povorcitinib at 45 mg once daily or 75 mg once daily or placebo during the 12-week placebo-controlled period. This was followed by a 42-week blinded extension through week 54, wherein patients in the placebo arm crossed over to povorcitinib. Patients had to have an abscess and inflammatory nodule (AN) count of ≥5 in at least two anatomic areas, Hurley stage II or III, disease duration ≥3 months, and prior systemic therapy.
Of the patients, 457 (37.2 percent) had previously received ≥1 dose of any biologic therapy for HS, including anti-TNF (n=364), anti–IL-17 (n=174), and other biologics (n=58), regardless of their response to these treatments.
The anti-TNF–experienced patient subpopulation was defined as those with an inadequate response (≥3 months of continuous treatment), intolerance, or contraindication to an anti-TNF biologic therapy. Of the 364 patients who received anti-TNF treatment, 329 (90.4 percent) met the subpopulation criteria and were included in the present analysis.
The median age in this subpopulation was 39 years, and most were female (63.5 percent), White (73.3 percent), and current smokers (45.6 percent). The mean BMI was 33.7 kg/m2, and 20.1 percent had severe obesity.
Generally, anti-TNF–experienced patients had higher disease severity at baseline compared with the overall population, as evidenced by higher AN (14.3 vs 12) and draining tunnel (3.7 vs 2.8) counts, mean disease duration (12.3 vs 10.3 years), percentage of Hurley stage III patients (48 percent vs 35.1 percent), percentage of those with prior HS excision surgery (28 percent vs 20.9 percent), mean Skin Pain NRS (6 vs 5), and mean HiSQoL score (37.3 vs 31.7).
Furthermore, a relatively high percentage of anti-TNF–experienced patients had previously received a second biologic drug (anti–IL-17: 23.7 percent; other biologics: 12.5 percent).