JAKi Treatment for Psoriatic Arthritis Not Associated With Increased CVD, VTE, Cancer Risk

JAK inhibitor (JAKi) therapy was not associated with an increased risk of cardiovascular disease, venous thromboembolism (VTE), or some cancers in people with psoriatic arthritis (PsA) and spondyloarthritis (SpA) compared to TNF inhibitors (TNFi) or IL-17 inhibitors (IL-17i).1

“Compared to TNFi, tofacitinib was shown to increase risk of CVD and cancer among people with rheumatoid arthritis (RA) with risk of CVD. Although JAKi are widely used in SpA, their safety profile remains unclear. Risk profiles may differ among SpA patients who are typically younger and have lower systemic inflammatory burden,” lead investigator Sizheng Steven Zhao, MBChB, PhD, Clinical Lecturer at the Centre for Musculoskeletal Research, University of Manchester, United Kingdom, and colleagues wrote.1

Zhao and colleagues analyzed data from a large population of patients in the TriNetX Global Collaborative Network, a large electronic health record network including over 100 million patients mostly in the United States. The study included adults with SpA, including axial SpA and PsA, and excluding those with RA or juvenile idiopathic arthritis, who initiated JAKis such as tofacitinib or upadacitinib, and TNFi, or IL-17is such as secukinumab or ixekizumab. They looked at rates of CVD,including acute myocardial infarction or cerebral infarction; VTE, including pulmonary embolism or deep vein thrombosis; and cancers including breast, colorectal, lung, or prostate. They also included herpes zoster as a positive control outcome. On statistical analyses, investigators corrected for age, gender, ethnicity (white vs non-white), BMI (<25, 25-30, >30kg/m2, missing), C-reactive protein (<5, 5-10, >10 mg/dL, missing), axSpA/PsA, hypertension, tobacco use, Chronic obstructive pulmonary disease (as proxy for smoking), overweight/obesity, type 2 diabetes mellitus, dyslipidaemia, and extra-musculoskeletal manifestations (uveitis, psoriasis, Crohn disease, ulcerative colitis). Intention to treat analyses were performed at 1, 3 and 5 years, as the stop date of each drug was not reliably available.1

Zhao and colleagues analyzed data from 2849 patients with SpA starting JAKi (mean age, 51 years [standard deviation (SD), 13]; 35% male; 80% white) and 32,694 patients with SpA starting TNFi (mean age, 48 years [SD, 14]; 49% male; 75% white). After propensity-score matching, 2844 remained in each group. Compared to TNFi, initiation of JAKi was not associated with risk of CVD (hazard rate [HR], 0.779 [95% CI, 0.547-1.108]), VTE (HR, 0.827 [95% CI, 0.480-1.425]) or cancer (HR, 0.820 [95% CI, 0.546-1.231) at 1 year, but was associated with a higher risk of herpes zoster (HR, 1.855 [95% CI, 1.151-2.991).1

When comparing patients initiating JAKi to 13,390 initiating IL17i (mean age, 50 years [SD, 13]; 42% male; 75% white), 2,792 in each group remained after propensity score-matching. Compared to IL17i initiation, JAKi initiation was not associated with risk of CVD (HR, 1.083 [95% CI, 0.732-1.603), VTE (HR, 0.900 [95% CI, 0.504-1.607) or cancer (HR, 0.890 [95% CI, 0.588-1.348) at 1 year. Findings on all analyses were directionally concordant for years 3 and 5.1

Other recent research on an IL-17i, secukinumab, found that intravenous (IV) secukinumab for the rapid improvement of disease signs and symptoms in patients with active PsA. Investigators found that all primary and secondary efficacy endpoints for secukinumab achieved statistical significance (all adjusted P <.05) versus placebo. A significantly greater proportion of patients receiving IV secukinumab achieved the primary endpoint of ACR50 response rates at Week 16 compared with placebo (31.4% vs. 6.3%; adjusted P <.0001).2

REFERENCES

1. Zhao SS, Riley D, Austin P, Alam U. Comparative Safety of Jak Inhibitors Versus TNF or Il-17 Inhibitors for Cardiovascular Disease, Venous Thromboembolism and Cancer in Psoriatic Arthritis and Axial Spondyloarthritis. Ann. Rheumatic. Dis. 2024;83:352.

2. Kivitz A, Sedova L, Churchill M, et al. Efficacy and Safety of Intravenous Secukinumab for the Treatment of Active Psoriatic Arthritis: Results From the Randomized, Placebo-Controlled Phase III INVIGORATE-2 Study. Arthritis Rheumatol. Published online September 19, 2024. doi:10.1002/art.42997