Risankizumab More Efficacious Than Apremilast for Moderate Plaque Psoriasis

Risankizumab was found to be superior to apremilast for the treatment of moderate plaque psoriasis including in patients who had not benefited from prior apremilast treatment, according to study results published in the British Journal of Dermatology.

Risankizumab, a humanized IgG1 monoclonal antibody that inhibits the regulatory cytokine IL-23, has previously shown superior efficacy to adalimumab, ustekinumab, and secukinumab in the treatment of psoriasis.

Researchers sought to compare the efficacy and safety of risankizumab vs apremilast in adult patients with moderate plaque psoriasis. They also aimed to evaluate the efficacy and safety of switching to risankizumab vs continuing apremilast among patients who had failed to reach at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75 nonresponders) after treatment with apremilast for 16 weeks.

The researchers conducted a phase 4, open-label, 52-week, randomized, assessor-blinded study (ClinicalTrials.gov Identifier: NCT04908475) which included 352 adult patients (at least 18 years of age) with moderate chronic plaque psoriasis (at least 6 months, with or without psoriatic arthritis) who were candidates for systemic therapy. Patients were enrolled in Canada, Germany, Israel, Poland, and the United States at 51 sites. They were randomly assigned in a 1:2 ratio to receive subcutaneous risankizumab at a dose of 150 mg at weeks 0 and 4 (n=118) or oral apremilast at a dosage of 30 mg twice daily (n=234). Moderate psoriasis was defined as a static Physician’s Global Assessment (sPGA) score of 3. In the overall study population, mean (SD) age was 46 (14) years, approximately 66% of patients were men, and almost one-third had received prior biologic and/or systemic therapy. Mean (SD) baseline PASI was 14.5 (2.6), and mean body surface area involvement was 13.1% (1.7).

Primary endpoints at week 16 (Period A) were achievement of PASI 90 and sPGA 0/1 (clear/almost clear) with at least a 2-grade improvement from baseline. The primary endpoint at week 52 (Period B) was achievement of PASI 90 among PASI 75 nonresponders treated with apremilast at week 16.

PASI 90 was achieved at week 16 by 55.9% (95% CI, 47.0% to 64.9%) of patients in the risankizumab group vs 5.1% (95% CI, 2.3% to 8.0%) of those in the apremilast group. Additionally, sPGA 0/1 was achieved by 75.4% of patients treated with risankizumab vs 18.4% of those treated with apremilast.

At week 16, patients in the apremilast group were all stratified by PASI 75 response and randomly reassigned 1:1 to treatment with risankizumab (82 nonresponders, 20 responders) or apremilast (75 nonresponders, 22 responders). Among those in the apremilast PASI 75 group who were nonresponders at week 16 (Period B), 83 switched to risankizumab and 78 continued treatment with apremilast. At week 52, among patients who switched to risankizumab, 72.3% achieved PASI 90 vs 2.6% who continued to receive apremilast.

In Period A, approximately 42% of patients treated with risankizumab and 61% of patients treated with apremilast reported treatment-emergent adverse events (TEAEs), of which 5% vs 42%, respectively, were possibly related to study treatment. There were no treatment discontinuations due to AEs in the risankizumab group vs approximately 7% of patients discontinuing treatment in the apremilast group.

In Period B, TEAEs were reported in approximately 56% of patients who switched from apremilast to risankizumab and in 46% of patients who continued to receive apremilast. Severe AEs were higher with risankizumab vs apremilast (2.9% vs 2.1%, respectively). Among patients treated with risankizumab, the most frequently reported adverse events were COVID-19 and nasopharyngitis. Patients treated with apremilast most frequently reported diarrhea, nausea, and headache.

Limitations of this study include its open-label design, possible bias towards retention of patients who experienced improved efficacy and for whom there were no safety concerns, the fact that most comparisons were performed without adjusting for multiplicity, and a lack of long-term follow-up. The researchers also emphasized that, to enhance the generalizability of the results, future studies should enroll cohorts that are more ethnically and geographically diverse.

“These results show that risankizumab, administered every 12 weeks, can be used to achieve high rates of clinical response, with favourable safety and tolerability compared to apremilast,” the researchers concluded. They added, “Improved patient-reported outcomes measuring health-related QOL, treatment satisfaction, and work productivity further support the favorability of risankizumab relative to apremilast in the systemic-eligible moderate psoriasis patient population.”

Disclosure: This research was supported byAbbVie. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Dermatology Advisor