TY - JOUR

T1 - Orismilast for the treatment of mild to severe hidradenitis suppurativa

T2 - Week 16 data from OSIRIS, a Phase 2a, open-label, single-centre, single-arm, dose-finding clinical trial

AU - Frederiksen, C. G.

AU - Sedeh, F. B.

AU - Taudorf, E. H.

AU - Saunte, D. M.

AU - Jemec, G. B. E.

N1 - Publisher Copyright: © 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

PY - 2024

Y1 - 2024

N2 - Background: Hidradenitis suppurativa (HS) is a disease with an unmet need for treatment. Objective: To examine tolerability, safety and efficacy of oral phosphodiesterase-4 (PDE4) inhibitior orismilast 10–40 mg twice daily (BID) in HS. Methods: A Phase 2a, single-arm, single-centre, open-label, 16-week trial in HS patients. Adjustments in maximal dose and titration were allowed, to improve tolerability, dividing the study population in two groups who completed and discontinued 16 weeks of treatment. Descriptive statistics were applied to efficacy data from patients who completed treatment and patients who discontinued treatment prematurely. A last-observation-carried-forward (LOCF) approach was used for patients who discontinued treatment. The primary endpoint was percent change in the total number of abscesses and nodules (AN-count) at Week 16, with the HS Clinical Response with a 50% reduction in the AN-count (HiSCR50) as key secondary endpoint. Results: Of the 20 patients included, 9 completed 16 weeks of treatment and 11 discontinued treatment prematurely. The mean AN-count was reduced with 33.1% in patients who completed treatment and with 12.0% in patients who discontinued. HiSCR50 was achieved by 67.0% and 27.0% of patients who completed and discontinued treatment, respectively. Most adverse events were mild to moderate. Conclusions: Oral orismilast demonstrated a dose-dependent tolerability, with mild to moderate adverse effects. Further, the results of this exploratory trial indicate that orismilast may lead to clinical improvements in HS. However, larger trials with tolerable dose ranges are warranted. The Trial is registered at Clinicaltrials.gov (UNI50007201) and EudraCT.ema.europa.eu (2021-000049-42).

AB - Background: Hidradenitis suppurativa (HS) is a disease with an unmet need for treatment. Objective: To examine tolerability, safety and efficacy of oral phosphodiesterase-4 (PDE4) inhibitior orismilast 10–40 mg twice daily (BID) in HS. Methods: A Phase 2a, single-arm, single-centre, open-label, 16-week trial in HS patients. Adjustments in maximal dose and titration were allowed, to improve tolerability, dividing the study population in two groups who completed and discontinued 16 weeks of treatment. Descriptive statistics were applied to efficacy data from patients who completed treatment and patients who discontinued treatment prematurely. A last-observation-carried-forward (LOCF) approach was used for patients who discontinued treatment. The primary endpoint was percent change in the total number of abscesses and nodules (AN-count) at Week 16, with the HS Clinical Response with a 50% reduction in the AN-count (HiSCR50) as key secondary endpoint. Results: Of the 20 patients included, 9 completed 16 weeks of treatment and 11 discontinued treatment prematurely. The mean AN-count was reduced with 33.1% in patients who completed treatment and with 12.0% in patients who discontinued. HiSCR50 was achieved by 67.0% and 27.0% of patients who completed and discontinued treatment, respectively. Most adverse events were mild to moderate. Conclusions: Oral orismilast demonstrated a dose-dependent tolerability, with mild to moderate adverse effects. Further, the results of this exploratory trial indicate that orismilast may lead to clinical improvements in HS. However, larger trials with tolerable dose ranges are warranted. The Trial is registered at Clinicaltrials.gov (UNI50007201) and EudraCT.ema.europa.eu (2021-000049-42).

U2 - 10.1111/jdv.19770

DO - 10.1111/jdv.19770

M3 - Journal article

C2 - 38147438

AN - SCOPUS:85180910063

VL - 38

SP - 920

EP - 930

JO - Journal of the European Academy of Dermatology and Venereology

JF - Journal of the European Academy of Dermatology and Venereology

SN - 0926-9959

IS - 5

ER -