Mirikizumab for plaque psoriasis: Results from OASIS-1

Mirikizumab, an interleukin (IL) 23 inhibitor, has previously shown superior efficacy to the IL-17 inhibitor secukinumab in the phase III OASIS-2 trial (NCT03535194) in patients with moderate to severe psoriasis. Here, we present the results of the placebo-controlled phase III OASIS-1 trial (NCT03482011) that investigated mirikizumab in patients with plaque psoriasis for up to 52 weeks.

Study design

OASIS-1 was a randomized double-blind trial, a 16-week induction period was followed by a 36-week maintenance period. After the induction period, responders and non-responders were spilt into different treatment groups for the maintenance period. Response was defined as achievement of ≥90% improvement in Psoriasis Area and Severity Index (PASI 90). Enrolled patients were ≥18 years old with a diagnosis of plaque psoriasis at least 6 months before baseline. The study design in shown in Figure 1.

Figure 1. OASIS-1 study design* 

BSA, body surface area; IL, interleukin; PASI, psoriasis area and severity index; sPGA, static physician’s global assessment; TNF, tumor necrosis factor; Q4W, every four weeks; Q8W, every eight weeks.
*Adapted from Blauvelt, et al.¹

The primary outcomes were the proportion of mirikizumab treated patients achieving a static physician’s global assessment (sPGA) score of 0 or 1 compared with placebo at Week 16, a ≥2-point improvement from baseline, and the proportion of patients achieving PASI 90.

Results

Baseline patient characteristics for both study periods are shown in Table 1. The majority of patients in all treatment groups were male, with a mean psoriasis duration of between 17 and 19 years.

Table 1. Baseline patient characteristics

Safety

During the induction period of OASIS-1, the rate of treatment-emergent adverse events (TEAEs) was similar in both mirikizumab and placebo treated patients; most TEAEs were mild or moderate and no deaths were reported. In the maintenance period, there was a higher rate of TEAEs reported in patients treated with mirkizumab 250 mg or 125 mg compared with patients who switched to placebo. TEAE rates and other safety outcomes in both study periods is shown in Figure 2.

Figure 2. Safety outcomes in A the induction period and B the maintenance period* 

AE, adverse event; TEAE, treatment-emergent adverse event.

*Adapted from Blauvelt, et al.¹

The most common TEAEs across both periods were headaches, injection-site pain, nasopharyngitis, and upper respiratory tract infection. There was a higher rate of infections and infestations in mirkizumab treated patients (27.5%) compared with placebo treated patients (19.6%) in the induction period. This trend was also observed in the maintenance period, where patients treated with mirikizumab (125 mg and 250 mg) had a higher rate of infections and infestations (38% and 43%, respectively) than placebo treated patients (30%). Adverse events of special interest are shown in Table 2.

Table 2. Adverse events of special interest*

Efficacy

The primary outcomes of the study were met, with a significantly greater proportion of mirikizumab treated patients achieving sPGA (0,1) and PASI 90 at Week 16 compared with placebo. The primary efficacy outcomes are shown in Figure 3, alongside the Week-52 outcomes.

Figure 3. Primary efficacy outcomes* 

PASI 90, ≥ 90% improvement in Psoriasis Area and Severity Index; sPGA, static Physician’s Global Assessment.
*Adapted from Blauvelt, et al.¹

Secondary efficacy endpoints were met in the induction period, with a significantly greater proportion of mirikizumab treated patients achieving PASI 75 compared with placebo at Week 4 (17% vs 0.9%) and Week 16 (82.5% vs 9.3%). At Week 52, there were significantly more mirikizumab treated patients compared with placebo who achieved PASI 100 (mirikizumab 250 mg, 85%; mirikizumab 125 mg, 86%; placebo, 19%). For patients receiving placebo in the maintenance period who received mirikizumab 250 mg in the induction period, the median time to loss of PASI 90 was 20.1 weeks.

Conclusion 

The OASIS-1 trial demonstrated that treatment with mirikizumab produced higher response rates in patients with plaque psoriasis compared with placebo, with efficacy maintained up to Week 52. Mirikizumab treatment was superior to placebo in all primary and secondary efficacy endpoints, with a similar rate of TEAEs and discontinuations across treatment arms. In addition, maintenance doses of either 125 mg or 250 mg mirizumab had similar efficacy. The efficacy and safety data of mirikizumab in this study is similar to previously published data on IL-23 inhibitors. Considering the large size of this study and inclusion of patients from several countries, these results suggest mirikizumab could be an effective treatment for patients with plaque psoriasis, despite the lack of an active comparator arm in the study.

Despite the success of the OASIS trials, psoriasis is no longer being pursued as an indication for mirikizumab.²