Treatment of hidradenitis suppurativa (HS) with oral orismilast may be well-tolerated and lead to clinical improvement dependent on dosage, according to new findings, though larger studies may be warranted.¹

These findings were observed in a recent study designed to assess HS patients’ response to the use of oral phosphodiesterase-4 (PDE4) inhibitior orismilast, specifically with a dose of 10–40 mg twice per-day. The research was led by CG Frederiksen, from the Department of Dermatology at the University Hospital of Zealand in Roskilde, Denmark.

Frederiksen and colleagues noted that secukinumab’s response rate—previously shown to be around 42.0%–46.0%—demonstrated an unmet need for newer therapy options for individuals facing HS.²

“Orismilast is an oral PDE4-inibitor holding potential for improved efficacy compared to currently available PDE4-inhibitors,” Frederiksen and colleagues wrote. “This trial assesses tolerability, safety and efficacy of oral orismilast in HS, and represents the first treatment experience with orismilast in patients with HS.”³

Background and Findings

The research team determined those aged 18 years or older with mild to severe HS—based on the International HS Severity score (IHS4-score)—to be eligible as participants in the phase 2a, single-center, open-label, single-arm trial. The research was conducted at Zealand University Hospital in Denmark.

The team used a screening period which took place over 4 weeks, followed by a 16-week treatment period, and finally by a 14-week follow-up period. They enrolled the subjects from October 2021 - December 2022, and the week 16 (W16) visit (the final one) was done in March 2023.

The investigators decided the main goal of their work would be to assess the tolerability of the proposed drug dosing regimen in those with HS. Consequently, they made changes in dosage over time to allow for tolerability.

While subjects were first given a 40 mg twice-per-day (BID) dose over a 2-week course, the research team found that the quick escalation ended up leading to unacceptable tolerability problems, especially gastrointestinal adverse effects (AEs) and later discontinuations of the drug.

They then determined they would use an individualized method in which a slower titration and a lower end-dose would be given to the 14 subjects who were left. The team also made evaluations of AEs, adverse reactions to treatment, and serious adverse events (SAEs) through various methods.

The investigators determined the measured percent change from the point of baseline in participants’ AN-count at W16 would be their main endpoint in the research. For their secondary endpoints, the research team looked at W16 or upon the time they discontinued.

At W16, the team assessed subjects’ IHS4-scores and their Hidradenitis Suppurativa Clinical Response. The latter would be a reduction of 50%, 75%, or 100% in the participants’ total AN-count (HiSCR50, HiSCR75, and HiSCR100), in addition to global assessment of skin pain through the use of Hidradenitis Suppurativa quality-of-life score (HiSQOL), numerical rating scale (NRS), and Dermatology quality-of-life index (DLQI).

Among the 20 individuals recruited as the study’s subjects, the investigators found that 9 were able to finish the 16 total weeks of orismilast therapy and 11 were shown to have terminated the program ahead of schedule.

Overall, the research team reported that the mean AN-count indicated that there was a 33.1% reduction for the participants who were able to finish their treatment and 12.0% for those who discontinued therapy.

Lastly, the team noted that HiSCR50 had been seen in 67.0% and 27.0% of the study participants who finished treatment and terminated treatment, respectively. They added that most of the AEs seen in the research were shown to be mild to moderate AEs.

“The results of this small trial suggest that PDE4B/D-inhibition with orismilast may lead to clinical improvements in HS,” they wrote. “However, larger trials at the most tolerable dose ranges are warranted based on the results of this exploratory trial. The safety profile was similar to what was seen with orismilast in psoriasis, and for other PDE4-inhibitors.”

References

1. ^{Frederiksen CG, Sedeh FB, Taudorf EH, Saunte DM, Jemec GBE. Orismilast for the treatment of mild to severe hidradenitis suppurativa: Week 16 data from OSIRIS, a Phase 2a, open-label, single-centre, single-arm, dose-finding clinical trial. J Eur Acad Dermatol Venereol. 2023; 00: 1–11. https://doi.org/10.1111/jdv.19770.}
2. ^{Kimball AB, Jemec GBE, Alavi A, Reguiai Z, Gottlieb AB, Bechara FG, et al. Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials. Lancet [Internet]. 2023; 401(10378): 747–761.}
3. ^{Silverberg JI, French LE, Warren RB, Strober B, Kjøller K, Sommer MOA, et al. Pharmacology of orismilast, a potent and selective PDE4 inhibitor. J Eur Acad Dermatol Venereol. 2022; 37: 721–729.}