Selective TYK2 inhibitor safe, works against psoriatic arthritis

Deucravacitinib, a selective TYK2 inhibitor, is well tolerated and appears to produce marked improvements in American College of Rheumatology 20 (ACR20) and other endpoints in the treatment of patients with psoriatic arthritis (PsA), according to the results of a phase II study.

A total of 203 PsA patients (mean age 49.8 years, 51.2 percent female, 98 percent Caucasian) were randomized to receive placebo (n=66) or deucravacitinib 6 mg (n=70) or 12 mg (n=67) once daily. The mean body weight was 88.6 kg.

Of the patients, 65.0 percent were being treated with conventional synthetic disease-modifying antirheumatic drug at baseline, and 15.8 percent had previously received a tumour necrosis factor inhibitor.

Overall, the median PsA duration was 4.5 years, the mean swollen joint count was 11.3, and the mean tender joint count was 18.1. There were 47.3 percent of patients with enthesitis and 38.9 percent with dactylitis. The mean PASI score was 8.5 among those with body surface area of involvement ≥3 percent.

The primary endpoint of ACR-20 response at the initial week 16 follow-up was significantly higher with both deucravacitinib doses than with placebo (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). Furthermore, active treatment led to significant improvements in the secondary endpoints of Health Assessment Questionnaire-Disability Index score, Short Form-36 Physical Component Summary score, and Psoriasis Area and Severity Index-75 response.

In terms of safety, nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache, and diarrhoea were the most common adverse events (AEs; ≥5 percent) among deucravacitinib-treated patients. None of the them developed serious AEs or herpes zoster, opportunistic infections, and major adverse cardiovascular events.

Mean changes in laboratory parameters were comparable between deucravacitinib and placebo.

Larger trials over longer periods of time with deucravacitinib are required to establish its safety profile and benefits in PsA.