Efficacy and safety of mirikizumab in psoriasis: results from a 52-week, double-blind, placebo-controlled, randomized withdrawal, phase III trial (OASIS-1)

Abstract

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. What is already known about this topic? Interleukin (IL)-23 is a key cytokine in the pathogenesis of psoriasis. Drugs targeting the p19 subunit of IL-23 have recently been approved for the treatment of adult patients with moderate-to-severe plaque psoriasis. Patients with moderate-to-severe plaque psoriasis achieved significantly greater improvements in skin measures and patient-reported quality-of-life measures after 16 weeks when treated every 8 weeks with mirikizumab compared with placebo in a phase II clinical trial. What does this study add? Compared with placebo, mirikizumab demonstrated high levels of efficacy at week 16 in a large phase III trial; safety profiles were similar between the mirikizumab and placebo arms. After week 16, patients maintained on doses of mirikizumab 250 mg every 8 weeks (Q8W) or 125 mg Q8W showed similar efficacy and favourable safety profiles over 52 weeks, whereas patients switched to placebo gradually lost efficacy over time.

Figure 1

CONSORT diagram: study patient disposition during the induction and maintenance periods. D/C, discontinued; ITT, intention to treat; Miri, mirikizumab; Q4W, every 4 weeks; Q8W, every 8 weeks. ^aIncludes eight patients who met the relapse criteria at week 52 and then completed the maintenance period without retreatment. ^bThe eight patients who met the relapse criteria at week 52 and then completed the maintenance period without retreatment are not included here.

Figure 2

Proportion of patients achieving clinical response and improvement in patient‐reported outcomes and health‐related quality‐of‐life during the induction period. (a) Static Physician’s Global Assessment (sPGA) score of 0 or 1. (b) ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90). (c) PASI 75. (d) PASI 100. (e) Involved body surface area (BSA) ≤ 1%. (f) Psoriasis Symptoms and Signs (PSS) symptoms free. (g) Dermatology Life Quality Index (DLQI) score of 0 or 1. Miri, mirikizumab; Pbo, placebo; Q4W, every 4 weeks. *P < 0·05 for mirikizumab vs. placebo using the Cochran–Mantel–Haenszel test stratified by prior biologics, weight and region.

Figure 3

Proportion of patients maintaining or achieving (a) ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90), (b) PASI 100 or (c) static Physician’s Global Assessment (sPGA) score of 0 or 1 during the maintenance period. The time of last dose prior to randomization is week 12. Miri, mirikizumab; Pbo, placebo; Q8W, every 8 weeks. ^† P < 0·05 for mirikizumab 250 mg/mirikizumab 250 mg vs. mirikizumab 250 mg/placebo; ^‡ P < 0·05 for mirikizumab 250 mg/mirikizumab 125 mg vs. mirikizumab 250 mg/placebo using the Cochran–Mantel–Haenszel test stratified by weight.

Figure 4

Time to first loss of ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) response through week 52. Maintenance period, rerandomized maintenance intention‐to‐treat population (OASIS‐1). The time of last dose prior to randomization is week 12. CI, confidence interval; HR, hazard ratio; MIRI, mirikizumab; NA, not applicable; Q8W, every 8 weeks. The numbers of patients at risk in brackets represent the number, of those being assessed, who lost or did not maintain PASI 90. ^aHR stratified by bodyweight (< 100 kg or ≥ 100 kg). ^b P‐value (two sided): log‐rank test for comparison with placebo Q8W stratified by bodyweight (< 100 kg or ≥ 100 kg).

Figure 5

Time to relapse through week 52. Maintenance period, rerandomized maintenance intention‐to‐treat population (OASIS‐1). The time of last dose prior to randomization is week 12. CI, confidence interval; HR, hazard ratio; MIRI, mirikizumab; NA, not applicable; Q8W, every 8 weeks. The numbers of patients at risk in brackets represent the number, of those being assessed, who lost or did not maintain ≥90% improvement in Psoriasis Area and Severity Index. ^aHR stratified by bodyweight (< 100 kg or ≥ 100 kg). ^b P‐value (two sided): log‐rank test for comparison with placebo Q8W stratified by bodyweight (< 100 kg or ≥ 100 kg).