Risankizumab shows superior efficacy to apremilast in moderate psoriasis: Results of the H2H phase 4 IMMpulse study

25 Aug 2023

Recently published in the British Journal of Dermatology, the head-to-head phase 4 IMMpulse study has demonstrated the superior efficacy of risankizumab, a humanized monoclonal antibody that inhibits interleukin-23 (IL-23), over apremilast in patients with moderate plaque psoriasis.1 “These data reinforce the efficacy of risankizumab for use in systemic-eligible patients with a safety profile similar to prior studies,” said one of the key researchers.2

Psoriasis is a chronic proliferative and inflammatory skin disease characterized by erythematous plaques covered with silvery scales.3 It has a global prevalence ranging from 0.2% to 4.8%.3 Being a lifelong illness marked by relapse and remission, about 10%-60% of patients with psoriasis will experience recurrent disease.3 Currently, there is no cure for psoriasis, and the objective of treatment focuses on alleviating the symptoms of the condition in order to improve patients’ quality of life.3 The Psoriasis Area Severity Index (PASI) is the most widely used measurement tool for assessing the disease condition and treatment effectiveness.3 Despite the use of approved treatments, many patients still fail to achieve high levels of skin clearance, measured by PASI.1 For instance, apremilast, a small-molecule phosphodiesterase 4 (PDE-4) inhibitor, is a commonly used oral systemic therapy approved for the treatment of moderate-severe psoriasis.4 Yet, clinical studies have shown that only 29%-41% of apremilast-treated patients achieved ≥75% reduction from baseline PASI (PASI 75).4 There remained an unmet need for improved patient satisfaction with treatment and reduced disease burden.

Risankizumab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that inhibits IL-23 by selectively binding to its p19 subunit.1 Previous studies have shown that the majority of risankizumab-treated patients were able to achieve 90% improvement in their disease.1 Although risankizumab demonstrates superior efficacy to other psoriasis treatments, including adalimumab, ustekinumab, and secukinumab, evidence of comparison of risankizumab and apremilast is lacking.1

The IMMpulse study is a 52-week, phase 4, multicenter, randomized, open-label study which compared the efficacy of risankizumab and apremilast head-to-head in patients with moderate psoriasis.1 Eligible patients were adults who had a diagnosis of moderate chronic plaque psoriasis for ≥6 months and were candidates for systemic therapy.1 A total of 352 participants were randomized 1:2 to receive risankizumab 150mg (n=118) subcutaneously (SC) at week 0 and 4 and oral (PO) apremilast 30mg twice daily (n=234) (Period A).1 At week 16 (Period B), all apremilast-treated patients were re-randomized 1:1 to receive either risankizumab every 12 weeks or apremilast.1 The co-primary outcomes in Period A at week 16 were the achievement of PASI 90 and static Physician’s Global Assessment (sPGA) 0/1 with ≥2-grade improvement from baseline.1 The primary endpoint in Period B at week 52 was the achievement of PASI 90 in PASI 75 non-responders with apremilast at week 16.1

The results showed that at week 16 (Period A), 55.9% (95% CI: 47.0%-64.9%) of risankizumab-treated patients achieved PASI 90, significantly higher than 5.1% (95% CI: 2.3%-8.0%) of the apremilast arm.1 Likewise, a significantly higher proportion of patients in the risankizumab arm achieved sPGA 0/1 when compared with apremilast [75.4% (95% CI: 67.7%-83.2%) vs. 18.4% (95% CI: 13.4%-23.3%)].1 From week 16, 83 PASI 75 non-responders in the apremilast group switched to risankizumab, while 78 PASI 75 non-responders continued with apremilast.1 At week 52 (Period B), 72.3% (95% CI: 62.7%-81.9%) of PASI 75 non-responders who switched to risankizumab attained PASI 90, while only 2.6% (95% CI: 0%-6.1%) of those who continued with apremilast achieved PASI 90.1

The safety findings with risankizumab were consistent with the established safety profile, with no new safety signal identified.1 The most frequently reported adverse events (AEs) associated with risankizumab were coronavirus disease 2019 (COVID-19) and nasopharyngitis, while the most frequently reported AEs with apremilast were diarrhea, nausea, and headache.1

In summary, the head-to-head phase 4 IMMpulse study demonstrated the superior efficacy of risankizumab vs. apremilast in patients with moderate psoriasis.1 For patients who did not benefit from prior apremilast treatment, risankizumab administered every 12 weeks also provided similarly significant clinical benefits.1 These data further supported the preference for risankizumab for patients with moderate psoriasis who are eligible for systemic treatment.1

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