Mirikizumab efficacy to placebo for treating moderate-to-severe plaque psoriasis

Considering the above, Andrew Blauvelt, Oregon Medical Research Center, Portland, OR, USA, and colleagues set out to examine the safety and efficacy of mirikizumab, an interleukin-23 inhibitor, in adult patients having moderate-to-severe plaque psoriasis through 52 weeks in phase III randomized controlled trial. They found that at week 16, mirikizumab was superior to the placebo and efficacy was maintained through week 52, with no revelation of new safety signals.

The findings of the study were featured in the British Journal of Dermatology. 

"Mirikizumab, compared to the placebo, showed high efficacy levels at week 16 in a large phase III trial; the safety profiles were comparable between the mirikizumab and placebo arms," the researchers wrote in their study. "Patients maintained on 250 mg dose of mirikizumab every eight weeks (Q8W) or 125 mg Q8W, after week 16, showed comparable efficacy and favourable safety profile over 52 weeks." The patients who changed to placebo lost efficacy over time.

Psoriasis is immune-mediated, chronic, and inflammatory skin disease that affects about 125 million people worldwide. Approximately 90% of psoriasis patients need long-term therapy, creating a critical need for psoriasis treatments that not only clear psoriasis plaques in the short term but also demonstrate durable efficacy over time. New biologics have been reported showing a better long-term safety profile than conventional treatments, but the concern regarding the relapse time after drug withdrawal remains. Notably, differences were seen among patients concerning maintaining response after treatment interruption.

Mirikizumab is a humanized, immunoglobulin G4 monoclonal antibody that targets the p19 subunit of IL-23 and has shown clinical efficacy in phase II trials in psoriasis, Crohn's disease, and ulcerative colitis. Blauvelt and team evaluated the safety and effectiveness of mirikizumab in moderate-to-severe plaque psoriasis patients through 52 weeks, including time to relapse, maintenance of response, and recapture of efficacy following treatment withdrawal in a double-blind, placebo-controlled, randomized withdrawal, phase III trial (OASIS-1). In a phase III trial (OASIS-2) for patients with moderate-to-severe psoriasis, Mirikizumab showed efficacy for up to 52 weeks, including superiority over secukinumab, an IL-17 inhibitor.

The trial included 530 patients randomized in the ratio of 4:1 to receive subcutaneous mirikizumab 250 mg or placebo every four weeks (Q4W) through week 16. The superiority of mirikizumab vs placebo was measured on static Physician's Global Assessment (sPGA score of 0 or 1 with ≥ 2-point improvement) and ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90, responders) at week 16 (Coprimary endpoints).

Mirikizumab responders were rerandomized in the 1: 1: 1 to receive mirikizumab 250 mg every eight weeks (Q8W), mirikizumab 125 mg Q8W, or placebo Q8W in week 52. The evaluation of secondary endpoints was done evaluated at weeks 16 and 52. Safety was monitored in all patients.

The authors reported the following findings:

• All primary and critical secondary endpoints were met.
• At week 16, sPGA(0,1) responses were remarkably more significant with mirikizumab (69·3%) than with placebo (6·5%).
• PASI 90 response was also more significant with mirikizumab (64·3%) than with placebo (6·5%).
• In the mirikizumab arms, significantly more patients achieved PASI 75 and PASI 100 (mirikizumab 82·5% and 32·4%; placebo, 9·3% and 1, 0·9%, respectively).
• At week 52, PASI 100, PASI 90, and sPGA(0,1) responses were, respectively, mirikizumab 250Q4W/125Q8W (N = 90; 86%, 59%, 86%), mirikizumab 250Q4W/placeboQ8W (N = 91; 19%, 10%, 18%), and mirikizumab 250Q4W/250Q8W (N = 91; 86%, 60%, 82%).
• Rates of serious adverse events were comparable across treatments (induction: mirikizumab 1·2% vs placebo 1·9%; maintenance: mirikizumab 250Q4W/125Q8W 1%, mirikizumab 250Q4W/250Q8W 3% vs placebo 3%). There was no occurrence of deaths.

To conclude, at week 16, mirikizumab was superior to the placebo and maintained efficacy through week 52, with no identification of new safety signals. Retreatment of mirikizumab after drug withdrawal resulted in prompt recapture of effectiveness without safety concerns.

Reference:

Blauvelt A, Kimball AB, Augustin M, Okubo Y, Witte MM, Capriles CR, Sontag A, Arora V, Osuntokun O, Strober B. Efficacy and safety of mirikizumab in psoriasis: results from a 52-week, double-blind, placebo-controlled, randomized withdrawal, phase III trial (OASIS-1). Br J Dermatol. 2022 Dec;187(6):866-877. doi: 10.1111/bjd.21743. Epub 2022 Aug 10. PMID: 35791755.