Evaluating upadacitinib for the treatment of psoriatic arthritis

Psoriatic arthritis is an extra-cutaneous manifestation affecting up to 40% of psoriasis patients with multiple therapies recommended by international guidelines including conventional and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) as well as biologics. Janus kinase inhibitors (JAKis) have emerged as a unique therapeutic target with tofacitinib the first to gain FDA approval in 2017. The non-selectivity of older JAKis increases the risk of off-target effects such as suppression of hemopoiesis hence the rationale for more selective alternatives.This paper explores the use of upadacitinib (a selective JAK1 inhibitor) for the treatment of psoriatic arthritis. It covers its chemical properties, pharmacokinetics, pharmacodynamics, efficacy, safety and regulation.In our opinion, upadacitinib is set to play an important role in the treatment of psoriatic arthritis as demonstrated by the SELECT-PsA trials especially in patients with poor or non-response to current first-line therapies. It's JAK1 receptor selectivity promises a lower side effect profile compared to the older nonselective JAKis but this will require confirmation with long-term clinical trial data.