Vinod Chandran, MBBS, MD, DM, PhD
Patients with active PsA require early effective therapy to improve long-term outcomes. The choice of therapy should balance effectiveness and potential toxicity. Janus kinase (JAK) inhibitors are a relatively new class of drugs that have been shown to be efficacious in treating PsA, but there are concerns about safety. To evaluate the efficacy and safety of JAK inhibitors in patients with psoriatic disease, Yang and colleagues conducted a systematic review and meta-analysis of 17 phase 2/3 randomized controlled trials including 6802 patients with PsA or moderate to severe plaque psoriasis who received at least one JAK inhibitor. They demonstrated that, compared with placebo, JAK inhibitors were associated with a significantly higher American College of Rheumatology 20 response rate (relative risk [RR] 2.09; P < .00001), with the response being the highest for filgotinib (RR 2.40; P < .00001), followed by upadacitinib, tofacitinib, and deucravacitinib. However, the overall incidence of adverse events was higher with JAK inhibitors vs placebo (RR 1.17; P < .00001) and significantly higher with 10-mg vs 5-mg tofacitinib ( P = .03). Thus, JAK inhibitors are efficacious in the treatment of PsA but are associated with adverse effects, particularly at higher doses.
Safety is best assessed in real-world observational studies. Clinical trials have raised concerns about a higher cancer risk in rheumatoid arthritis (RA) patients treated with JAK inhibitors compared with patients treated with tumor necrosis factor (TNF) inhibitors. To evaluate this further, Huss and colleagues conducted an observational cohort study that evaluated prospectively collected data from national Swedish data sources on 4443 patients with PsA and 10,447 patients with RA, all without previous cancer, who received JAK inhibitors, TNF inhibitors, or other non–TNF inhibitor biologic disease-modifying antirheumatic drugs. Overall, use of JAK inhibitors vs TNF inhibitors was not significantly associated with a higher risk for cancer other than nonmelanoma skin cancer, especially in RA. In patients with PsA, there was a trend toward higher risk for nonmelanoma skin cancer, but it was not statistically significant. The study provides reassurance that JAK inhibitors are generally as safe, as are TNF inhibitors in PsA, but continued vigilance is required.
There are limited data on the effect of disease activity on pregnancy outcomes in individuals with PsA. Using data from the Medical Birth Registry of Norway linked to data from a Norwegian nationwide observational register recruiting women with inflammatory rheumatic diseases, Skorpen and colleagues evaluated the association of active disease and cesarean section (CS) rates in singleton births in women with PsA (n = 121), axial spondyloarthritis (n = 312), and controls (n = 575,798). Compared with control individuals, women with PsA had a higher risk for CS (risk difference [RD] 15.0%; P < .001) and for emergency CS (RD 10.6%; P < .001), with active disease in the third trimester further amplifying both risks (CS: RD 17.7%; P = .028; emergency CS: RD 15.9%; P = .015). Thus, although in many patients disease activity decreases during pregnancy, this study highlights the importance of pregestational counseling and disease control along with regular monitoring of PsA during pregnancy such that disease activity remains well controlled.