Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis

Abstract

To facitinib and baricitinib are two of the currently available Janus kinase (JAK) inhibitors for the treatment of patients with RA. Randomized controlled trials have shown that these JAK inhibitors are as efficacious as biological DMARDs. Safety profiles of these JAK inhibitors in randomized controlled trials and their long-term extension studies have been demonstrated; however, real world evidence remains to be established to bridge the gap between randomized controlled trials and rheumatology clinics. Fundamentally, no difference in the screening, prevention, and monitoring of infections between JAK inhibitors and biological DMARDs exists. However, increased risk of herpes zoster is probably common to all JAK inhibitors. No indication of increased risk for malignancy in patients with RA treated with JAK inhibitors has been reported. To evaluate risks of relatively rare serious adverse events such as thromboembolic events, gastrointestinal perforation, and interstitial lung disease in clinical settings, accumulation of cases with these events are needed. Continuous pharmacovigilance activity is absolutely warranted to establish the safety of JAK inhibitors in patients with RA and other rheumatic diseases.

Keywords: Janus kinase; RA; adverse event; baricitinib; herpes zoster; infection; malignancy; safety; thromboembolism; tofacitinib.

Fig. 1

Incidence rates of serious adverse events in patients with RA Incidence rates per 100 patient-years and 95% CIs of infection requiring hospitalization (for registries) or serious infection (for tofacitinib and baricitinib) (A) [11–13], all HZ, (B) [11, 12, 14], overall malignancy excluding non-melanoma skin cancer (C) [15–17], and lymphoma (D) [157–17] were plotted. Event rates in five large registries of RA (CORRONA, Institute of Rheumatology Rheumatoid Arthritis, Norfolk Arthritis Register, Swedish Rheumatology Quality of Care Register, and CORRONA International) were standardized for age and sex distribution in the RA clinical trial programme [11, 12]. For tofacitinib and baricitinib, crude incidence is presented. CORRONA: Consortium of Rheumatology Researchers of North America.