TYK2 inhibitor for psoriatic arthritis clears phase II trial

In the treatment of patients with psoriatic arthritis (PsA), the use of the selective TYK2 inhibitor deucravacitinib appears to be effective and well tolerated, leading to greater improvements in American College of Rheumatology (ACR) domains, enthesitis endpoints, and multiple patient-reported, psoriasis-related outcomes relative to placebo, as shown in the results of a phase II trial.

A total of 203 PsA patients (mean age 49.8 years, 51.2 percent female, 98 percent Caucasians, mean body weight 88.6 kg) were randomized to receive once-daily treatment with deucravacitinib 6 mg (n=70) or 12 mg (n=67) or placebo (n=66) for 16 weeks. Most of them (65.0 percent) were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) at baseline, and 15.8 percent had previously been exposed to a tumour necrosis factor inhibitor (TNFi).

The median PsA duration (from diagnosis) was 4.5 years, the mean swollen joint count was 11.3, and the mean tender joint count was 18.1. Enthesitis was present in 47.3 percent and dactylitis in 38.9 percent of patients. The mean PASI score was 8.5 in those with body surface area of involvement ≥3 percent.

Compared with placebo, both deucravacitinib doses resulted in a significantly higher ACR-20 response, the primary endpoint, at week 16 (52.9 percent with 6 mg and 62.7 percent with 12 mg vs 31.8 percent; p=0.0134 and p=0.0004, respectively).

Both deucravacitinib doses also led to greater improvements in the multiplicity-controlled secondary endpoints of change from baseline in Health Assessment Questionnaire-Disability Index and Short Form-36 Physical Component Summary score and in Psoriasis Area and Severity Index-75 response (p≤0.05).

The most common adverse events (AEs) observed among deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache, and diarrhoea. None of the patients in the active treatment groups developed serious AEs, herpes zoster, opportunistic infections, and major adverse cardiovascular events.