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