OASIS-1: Thumbs up for mirikizumab in moderate-to-severe plaque psoriasis

The interleukin (IL)-23 inhibitor mirikizumab demonstrates superior efficacy in the treatment of patients with moderate-to-severe plaque psoriasis as compared with placebo, with initial responses during induction preserved through the maintenance phase, according to the results of the phase III OASIS-1 trial.

“All primary and key secondary endpoints were met,” the investigators said.

Among 530 patients in OASIS-1, 69.3 percent of the patients who received subcutaneous mirikizumab 250 mg (293 of 423) achieved the co-primary endpoint static Physician’s Global Assessment (sPGA; score of 0 or 1 with ≥2-point improvement) response at week 16, as opposed to a mere 6.5 percent of the patients who received placebo (seven of 107; p<0.001). [Br J Dermatol 2022;doi:10.1111/bjd.21743]

The other coprimary endpoint of a ≥90-percent improvement in Psoriasis Area and Severity Index (PASI 90 response) also occurred more frequently in the mirikizumab group (64.3 percent vs 6.5 percent; p<0.001). Likewise, significantly more patients in the mirikizumab arms achieved the secondary endpoints PASI 75 (82.5 percent vs 9.3 percent) and PASI 100 (32.4 percent vs 0.9 percent; p<0.001).

During the maintenance treatment phase, mirikizumab responders were rerandomized to receive mirikizumab 250 mg every 8 weeks (Q8W), mirikizumab 125 mg Q8W, or placebo Q8W through week 52.

The respective PASI 90, PASI 100 and sPGA(0,1) responses at week 52 were 19 percent, 10 percent, and 18 percent in the mirikizumab 250Q4W/placeboQ8W arm (n=91); 86 percent, 59 percent, and 86 percent in the mirikizumab 250Q4W/125Q8W arm (n=90); and 86 percent, 60 percent, and 82 percent in the mirikizumab 250Q4W/250Q8W arm (n=91; p<0.001 for all).

“Mirikizumab, a humanized, immunoglobulin G4 monoclonal antibody, specifically targets the p19 subunit of IL-23 and has demonstrated clinical efficacy in phase II trials in psoriasis, ulcerative colitis, and Crohn’s disease,” according to the investigators. 

“Mirikizumab also demonstrated efficacy up to 52 weeks, including superiority over an IL-17 inhibitor (secukinumab), in a phase III trial (OASIS-2) for patients with moderate-to-severe psoriasis,” they added. [Br J Dermatol 2019;181:88-95; Gastroenterology 2020;158:537-549; Gastroenterology 2019;156:S216; Gastroenterology 2022;162:495-508; J Clin Aesthet Dermatol 2021;14:S8-30]

In OASIS-1, the investigators also noted that following an induction dose of 250 mg every 4 weeks, maintenance doses of 125 or 250 mg every 8 weeks from week 16 to week 52 proved to be comparable in terms of maintaining efficacy.

“Among patients who achieved PASI 90 at week 16 and were subsequently randomized to placebo, the median time to first loss of PASI 90 response was approximately 20 weeks and the median time to relapse was approximately 36 weeks,” the investigators said.

“These results are aligned with other clinical trials in patients with plaque psoriasis that also assessed time to loss of response after withdrawal of IL-23 inhibitors,” they added. [J Am Acad Dermatol 2017;76:418-431]

Demographics and disease characteristics were generally similar across treatment arms and study periods. Overall, patients were 46.3 years old, weighed 85 kg, had had psoriasis for 17.6 years, and had a baseline PASI of 22.6. Patients with severe (4) and very severe (5) baseline sPGA scores accounted for 42.1 percent and 8.7 percent of the total population, respectively. Meanwhile, 32.1 percent of the patients received biologic therapy previously.

“The overall safety profile of mirikizumab was consistent with the published safety data for other IL-23p19 inhibitors and with previously published data for mirikizumab in phase II and III trials,” the investigators said.

Rates of serious adverse events were similar across treatment arms: 1.2 percent with mirikizumab and 1.9 percent with placebo in the induction phase; 1 percent with mirikizumab 250Q4W/125Q8W, 3 percent with mirikizumab 250Q4W/250Q8W, and 3 percent with placebo in the maintenance phase. There were no cases of death.