Selective IL-23 blocker shows potential in psoriasis treatment

The IL-23p19 class antibody mirikizumab demonstrated superiority to placebo and non-inferiority to secukinumab in the treatment of psoriasis up to 52 weeks.

“Mirikizumab is a humanised, IgG4-variant monoclonal antibody binding to p19, thereby blocking IL-23,” explained Dr Kim Papp (Probity Medical Research, Canada). He reported on the primary and major secondary efficacy and safety outcomes of mirikizumab versus secukinumab and placebo in the treatment of psoriasis at week 52 [1]. The phase 3, randomised, multicentre OASIS-2 study (NCT03535194) included over 1,400 adult patients with moderate-to-severe plaque psoriasis. 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 in 2 arms, or secukinumab or placebo every 4 weeks. In the maintenance period, 1 of the mirikizumab arms switched to 250 mg every 8 weeks and the other to 125 mg every 8 weeks, while the secukinumab group remained on the per-label dosage. Patients initially treated with placebo, continued with mirikizumab 250 mg every 4 weeks from week 16 to week 32 and subsequently switched to an 8-weekly dosing.

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 and severity index (PASI) 90 improvement at week 16. Among the major secondary endpoints were the proportion of patients achieving PASI 75 and PASI 100. “Regarding age, gender, and weight, the distribution of patients was well balanced across all groups,” stated Dr Papp. The study arms also had a similar distribution regarding disease duration, sPGA, body surface area (BSA), PASI, and presence of psoriatic arthritis (PsA) at baseline.

Throughout the induction phase, overall treatment-emergent adverse events (TEAEs) 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%, and combined mirikizumab groups 77.1%; most of them being mild to moderate. The most common TEAEs were nasopharyngitis and upper respiratory tract infections. Serious AEs happened in 1.9% of the placebo group, 5.6% in the secukinumab group, and 3.9% in the mirikizumab 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 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 indicated. PASI 90 at this point was achieved by 74.4% of the mirikizumab every 4 weeks 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 proportions achieving PASI 90 were 82.4% and 81.4% in the 2 mirikizumab arms versus 69.4% in the secukinumab group, and 75% in the placebo arm. The sPGA and PASI 100 results followed a similar pattern.

In summary, the novel IL-23 blocker mirikizumab was judged significantly superior to placebo in the primary endpoint 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.

 

1. 
   
   1. Papp KA, 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. 3A, EADV 2020 Virtual Congress, 29-31 Oct.

 



Posted on 17 December 202018 December 2020