Risankizumab Outperforms Ustekinumab in Treating Psoriasis

Overview of Psoriasis

Psoriasis is a chronic immune-mediated inflammatory skin condition that affects approximately 2% of adults. The disease is linked to various health issues, including obesity, hypertension, diabetes, hypercholesterolemia, and metabolic syndrome. Research indicates that interleukin-23 (IL-23), which consists of p19 and p40 subunits, plays a crucial role in the disease by promoting and sustaining inflammatory cells.

Current Treatment Strategies

Treatment options for psoriasis include monoclonal antibodies targeting different subunits of IL-23. Ustekinumab is designed to target the p40 subunit, which is also present in IL-12, thus affecting both IL-23 and IL-12. In contrast, risankizumab selectively targets the p19 subunit, focusing solely on inhibiting IL-23 activity. Clinical studies have confirmed that both medications are safe, well-tolerated, and effective for psoriasis patients.

Clinical Trial Details

A recent randomized phase II clinical trial evaluated the efficacy, onset, and duration of clinical response of risankizumab compared to ustekinumab in patients with moderate-to-severe psoriasis. Participants were randomly assigned to receive either a single 18-mg dose of risankizumab at week 0, or 90-mg or 180-mg doses at weeks 0, 4, and 16, or a dose of ustekinumab at the same intervals. The total duration of the trial was 48 weeks, with follow-up for 32 weeks post-final injection. The primary endpoint was achieving a 90% or greater reduction from baseline in the Psoriasis Area Severity Index (PASI), which evaluates erythema, scaling, and the affected body-surface area. Additionally, the study monitored safety endpoints, including severe and moderate adverse events.

Results of the Trial

At the conclusion of the study, a 90% or greater reduction in PASI was achieved by 73% of patients in the 90-mg risankizumab group and 80% in the 180-mg group, in contrast to only 40% of those receiving ustekinumab. This indicates that both 90 mg and 180 mg doses of risankizumab are more effective in managing psoriasis than ustekinumab. Furthermore, the onset of action for risankizumab was observed to be quicker, with sustained benefits lasting longer. Patient reports and skin biopsies further supported the superiority of risankizumab in addressing psoriasis and its related morbidities.

Conclusion and Future Directions

The findings of the randomized phase II clinical trial suggest that risankizumab is more effective than ustekinumab in treating psoriasis and its associated conditions. The onset of therapeutic effects is quicker and more prolonged with risankizumab. Although there were reports of two patients developing basal-cell carcinoma and one experiencing a major cardiac event while on risankizumab, the study’s small sample size and short duration limit the assessment of safety profiles. Nonetheless, the results indicate that selective inhibition of IL-23 through p19 subunit blockade is a more effective strategy for psoriasis treatment than targeting both IL-23 and IL-12. Future research is necessary to validate these findings and further evaluate the safety profile of risankizumab.

Written By: Haisam Shah, BSc