Analysis of Infections and All‐Cause Mortality in Phase II, Phase III, and Long‐Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis

Abstract

Objective. To determine the rate of infection and all-cause mortality across tofacitinib phase II, phase III, and long-term extension (LTE) studies in patients with moderately to severely active rheumatoid arthritis (RA).Methods. Conclusion. The overall risk of infection (including serious infection) and mortality rates in RA patients treated with tofacitinib appear to be similar to those observed in RA patients treated with biologic agents. The rates of serious infection were stable over time. 550) is an oral JAK inhibitor used for the treatment of rheumatoid arthritis (RA) and has a novel mechanism of action. The JAK family of tyrosine kinases includes JAK-1, JAK-2, JAK-3, and Tyk-2. Tofacitinib preferentially inhibits signaling by heterodimeric receptors associated with JAK-3 and/or JAK-1, with functional selectivity over receptors that signal in pairs of JAK-2 (1). Common ␥-chaincontaining receptors using JAK-1 and JAK-3 include

Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

“…Recently reported risk factor analyses have shown that Asian patients exposed to tofacitinib had a higher IR of herpes zoster infection 49 . The rate of herpes zoster infection did not appear to increase after longterm treatment and followup 48 .…”

“…The IR for herpes zoster infection (serious and non-serious) was higher for tofacitinib [4.3 (95% CI: 3.83-4.90) per 100 patient-years] than the rates reported in the literature for patients with RA treated with biologic and nonbiologic DMARD (0.0034 to 2.4 events per 100 patient-years) 39,40,41,42,43,44,45,46 . It is noteworthy that the rates of herpes zoster in the phase III cohorts of patients receiving placebo and adalimumab in the tofacitinib program were also higher than those in the literature overall 47,48 . Recently reported risk factor analyses have shown that Asian patients exposed to tofacitinib had a higher IR of herpes zoster infection 49 .…”

“…The safety reported here relates only to findings in the LTE phase of the tofacitinib development program, with the exception of GI perforations, where an integrated analysis is presented (the majority of cases occurred in LTE studies). A detailed discussion of safety events of special interest is, however, warranted and will be addressed in dedicated safety reports in preparation, which will integrate safety findings from LTE, phase II, and phase III studies, to provide an integrated summary from across the development program 37,38,48,49,52,53 .…”

Risk of cytomegalovirus reactivation in patients with immune-mediated inflammatory diseases undergoing biologic treatment: a real matter?

“…We found one report describing two CMV infections in patients affected by psoriasis during anti-TNF-α therapy (12). In case of the novel therapies for RA, like Janus Kinase (JAK) inhibitors (tofacitinib), an analysis to determine the rate of infections reported 6 cases of CMV infection, but it's not clear if the clinical presentation was severe neither if it was a primary infection or a reactivation (13). In Table I, we summarize the cases of CMV infection reported during biological therapy in IMID patients.…”

Targeted Therapy and Infections in Rheumatic Diseases

“…При оценке эффективности и безопасности ТОФА у 3151 больного РА частота выявления HZ колебалась в пре-делах 5,4-7,7%, или 3,37-4,49 на 100 пациенто-лет. При этом HZ-инфекция фигурировала в качестве СКИ с часто-той 0,3 на 100 пациенто-лет [110].…”