IL-23p19 class antibody efficacious in psoriasis management

Mirikizumab is another selective IL-23 blocker that showed promise in the treatment of psoriasis with superiority to placebo and non-inferiority to secukinumab up to 52 weeks.

The phase 3, randomised, multicentre OASIS-2 study included over 1,400 adult patients with moderate-to-severe plaque psoriasis [1]. The study consisted of an induction period to week 16 and a blinded maintenance period lasting to week 52. Patients were initially randomised 4:4:4:1 to receive either 250 mg mirikizumab every 4 weeks (Q4W) in 2 arms, or secukinumab or placebo Q4W. Within the maintenance period, 1 of the mirikizumab arms switched to 250 mg and the other to 125 mg, both every 8 weeks, while the secukinumab group remained on the per label dosage. Patients initially treated with placebo continued with mirikizumab 250 mg Q4W from week 16 to week 32 and were changed to an 8 weekly dosing thereafter.

Primary endpoints were defined as the proportions of patients reaching static Physician Global Assessment (sPGA) 0/1 (i.e. clear or almost clear skin) and a psoriasis area severity index (PASI) 90 improvement at week 16. Among the major secondary endpoints were the rates achieving PASI 75 and PASI 100. “Regarding age, gender, and weight the distribution of patients was well balanced across all groups,” stated Dr Kim Papp (Probity Medical Research, Canada). The groups also had a similar distribution regarding disease duration, sPGA, body surface area (BSA), PASI, and presence of psoriatic arthritis at baseline.

Throughout the induction phase, overall treatment-emerging adverse events (TEAE) were 60.7% under placebo, 57.8% in the secukinumab arm, and 58.1% in the mirikizumab arms. The corresponding rates during the whole study period (week 0-52) were: placebo 71.2%, secukinumab 78.3%, combined mirikizumab groups 77.1%; the majority of them being mild to moderate. The most common TEAEs were nasopharyngitis and upper respiratory tract infections. Serious AE happened in 1.9% (placebo), 5.6% (secukinumab) and 3.9% (mirikizumab) of the groups.

“We see that during the induction period, secukinumab maintains a slight lead over mirikizumab in terms of PASI 90 response, but at approximately week 12 we see that there is a diminishing capability of secukinumab to achieve higher levels of PASI 90 response and mirikizumab quickly catches up, surpassing secukinumab at week 16,” Dr Papp stated. PASI 90 at this point was achieved by 74.4% of the mirikizumab Q4W arm and 72.8% of the secukinumab arm. “Secondly, we see in the secukinumab cohort a somewhat diminishing response over time leading to an even superior response level maintained by mirikizumab,” he continued. At week 52, the PASI 90 proportions were 82.4% and 81.4% in the 2 mirikizumab arms versus 69.4% in the secukinumab arm, and 75% in the placebo arm. sPGA and PASI 100 results followed a similar pattern.

In summary, the novel IL-23 blocker was judged significantly superior to placebo in the primary and non-inferior and superior to secukinumab in the secondary endpoints. “All this combined indicates that mirikizumab certainly warrants further evaluation in the treatment of chronic plaque psoriasis,” Dr Papp concluded.

 

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   1. Papp K, et al. Efficacy and safety of mirikizumab versus secukinumab and placebo in the treatment of moderate-to-severe psoriasis: 52-week results from OASIS-2, a multicenter, randomized, double-blind study. Late-breaker D1T03.3A, EADV Virtual, 29-31 October 2020.

Posted on 30 October, 202018 December, 2020