Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week integrated results from 2 phase 3, randomized, double-blind clinical trials for csDMARD-IR and bio-IR patients.
Authors: Andrew Ostor al.
Risankizumab is a humanized IgG1 antibody directed against the p19 subunit of IL-23. A total of 1407 patients were included in the KEEPsAKE 1 and 2 trials to compare efficacy and safety of risankizumab versus placebo in patients with active PsA. Patients received blinded subcutaneous risankizumab 150mg or placebo at baseline, week 4 and week 16. The primary endpoint (ACR20 at week 24) was reached significantly more frequent in patients who received risankizumab (55.5%) in comparison to placebo patients (31.3%), p < 0.001. Secondary endpoints included ACR 50, ACR 70, resolution of dactylitis and enthesitis, MDA, PASI90 or HAQ, and were achieved significantly more frequent in patients on active drug. Side effects including serious adverse events, MACE, serious infections or malignancies occurred in both treatment arms with comparable frequency.
bDMARDs currently benefit from the discussion about the safety of JAK inhibitors as the FDA issued a warning regarding all JAK inhibitors on their website. Thus far, no relevant side effects have been reported from trials using IL12/IL23 directed bDMARDs in patients with PsA. However, IL23 has been implied in airway inflammation and based on this concept, risankizumab was recently evaluated in a phase 2a trial in subjects with severe asthma. Almost unexpected, the time to first worsening of asthma was shorter and the annual rate of asthma worsening was higher with risankizumab than with placebo (Brightling CE et al, N Engl J Med 2021) An adverse effect of anti-IL23 directed therapies on asthma or CPOD in patients with PsA has thus far not been reported in any of the trials that have been presented to the rheumatology community. Did any of the patients in the KEEPsAKE trials suffer from severe asthma? Probably not as patients with serious comorbidities are usually not included in clinical trials. However, in real life daily practise, patients might suffer from more than one disease.