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.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

“…Screening for risk factors for LIP (eg, history of diverticulitis) is advised before initiating IL-6Ri 117. More long-term observational studies (with a proper comparator) are needed to clarify the risk of LIP with JAKi seen in previous pooled analyses of trial data 118–120…”

Review article: prevention, diagnosis and management of COVID‐19 in the IBD patient

“…Serious infection was found to be increased with tofacitinib in the induction trials for UC, but similar across treatment groups including placebo in the maintenance trial 91 . Of 4789 patients treated with tofacitinib in phase II, III and LTE studies, 259 patients had serious infections (3.09 events per 100 PY [95% CI 2.73, 3.49]), and the most common infection was pneumonia 92 . Higher doses of 10 mg twice daily as opposed to 5 mg twice daily, age >65 years, corticosteroids >7.5 mg/d and diabetes were also independent factors associated with increased serious infection risk 92,93 .…”

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…Baricitinib, at therapeutic dosing (either as 2 mg or 4 mg once daily) is sufficient to inhibit AAK1, thus it has been suggested to be trialed in an appropriated COVID population [6,292]. On the other hand, therapies targeting JAK complexes may interfere with normal anti-viral response including inhibition of IFN-γ activity and may potentially increase the risk of infection and/or reactivation of several viral infectious diseases [293][294][295], including a dose dependent risk for VZV observed for tofacitinib and baricitinib [296]. Thus, their usage should be carefully evaluated.…”