Abstract and Introduction
Background: Interleukin-23 inhibitors are effective and safe for treating moderate-to-severe plaque psoriasis.
Objectives: To evaluate the efficacy and safety of mirikizumab in adult patients with moderate-to-severe plaque psoriasis through 52 weeks in a phase III randomized controlled trial.
Methods: OASIS-1 (NCT03482011) was a double-blind, placebo-controlled, randomized withdrawal, phase III trial. Patients (n = 530, randomized 4 : 1) received subcutaneous mirikizumab 250 mg or placebo every 4 weeks (Q4W) through week 16. Coprimary endpoints were superiority of mirikizumab vs. placebo 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. Mirikizumab responders were rerandomized (1 : 1 : 1) to mirikizumab 250 mg every 8 weeks (Q8W), mirikizumab 125 mg Q8W, or placebo Q8W through week 52. Secondary endpoints were evaluated at weeks 16 and 52. Safety was monitored in all patients.
Results: All primary and key secondary endpoints were met. At week 16, sPGA(0,1) responses were significantly greater with mirikizumab (293 of 423, 69·3%) than placebo (seven of 107, 6·5%) (P < 0·001). PASI 90 response was also greater with mirikizumab (272 of 423, 64·3%) than placebo (seven of 107, 6·5%) (P < 0·001). Significantly more patients in the mirikizumab arms achieved PASI 75 and PASI 100 (mirikizumab 349, 82·5% and 137, 32·4%; placebo 10, 9·3% and 1, 0·9%, respectively; all P < 0·001). At week 52, PASI 90, PASI 100 and sPGA(0,1) responses were mirikizumab 250Q4W/placeboQ8W (N = 91; 19%, 10%, 18%), mirikizumab 250Q4W/125Q8W (N = 90; 86%, 59%, 86%) and mirikizumab 250Q4W/250Q8W (N = 91; 86%, 60%, 82%; all P < 0·001), respectively. Rates of serious adverse events were similar across treatments (induction: mirikizumab 1·2% vs. placebo 1·9%; maintenance: mirikizumab 250Q4W/125Q8W 1%, mirikizumab 250Q4W/250Q8W 3% vs. placebo 3%). No deaths occurred.
Conclusions: Mirikizumab was superior to placebo at week 16 and maintained efficacy through week 52, with no new safety signals.
Psoriasis is a chronic, immune-mediated, inflammatory skin disease that affects an estimated 125 million people worldwide. Approximately 90% of patients with psoriasis require 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 shown a better long-term safety profile than conventional treatments, but the time to relapse after drug withdrawal remains a concern. Notably, differences have been observed among patients in terms of maintaining response after treatment interruption.[4,5]
Since the discovery of the key roles of interleukin (IL)-17 and IL-23 in the development of psoriatic disease,[6,7] several biologic therapies that target these cytokines and associated inflammatory pathways have been studied and approved for use in patients with plaque psoriasis.[8–15] Therapies selectively targeting the p19 subunit of IL-23, such as guselkumab and risankizumab,[4,13] have resulted in high Psoriasis Area and Severity Index (PASI) response rates with favourable safety profiles,[4,13] and have shown prolonged maintenance of responses following randomized drug withdrawal.[4,14,16] This may be due to the ability of IL-23 inhibitors to decrease resident memory T cells within the affected tissue, which have been shown to be responsible for psoriasis recurrences after initial skin clearing.[18,19]
Mirikizumab (LY3074828), 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 disease.[22,23] Mirikizumab also demonstrated efficacy up to 52 weeks, including superiority over an IL-17 inhibitor (secukinumab), in a phase III trial (OASIS-2, NCT03535194) for patients with moderate-to-severe psoriasis. Here, we evaluated the efficacy and safety of mirikizumab in patients with moderate-to-severe plaque psoriasis through 52 weeks, including maintenance of response, time to relapse, and recapture of efficacy after treatment withdrawal in a double-blind, placebo-controlled, randomized withdrawal, phase III trial (OASIS-1, NCT03482011).
The British Journal of Dermatology. 2022;187(6):866-877. © 2022 Blackwell Publishing