Infections more common in patients with RA receiving tofacitinib vs TNF inhibitors
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Infections are more common in patients with rheumatoid arthritis who receive tofacitinib compared with those who receive TNF inhibitors, according to data published in the Annals of the Rheumatic Diseases.
“The increased susceptibility to infections in patients with RA has been attributed to disease pathophysiology, comorbidities, lifestyle factors and use of immunomodulatory drugs,” Andra-Rodica Balanescu, MD, of the Carol Davila University of Medicine and Pharmacy, in Bucharest, Romania, and colleagues wrote.
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“Analyses of real-world and clinical trial data from patients with RA have shown that the risk of serious and non-serious infections (NSIs) is increased in those receiving biologic disease-modifying antirheumatic drugs (bDMARDs) versus conventional synthetic DMARDs (csDMARDs), and the risk of infections varies across treatments,” they added.
To investigate the prevalence of infections in patients with RA, the Balanescu and colleagues analyzed data from the ORAL Surveillance study, a phase 3b/4 randomized, open-label, safety endpoint study that was conducted from March 2014 to July 2020. The study included patients with RA who demonstrated active disease despite receiving methotrexate. Eligible patients were aged 50 years or older and had at least one additional cardiovascular risk factor.
Patients were excluded if they developed an infection requiring intervention 2 weeks or fewer prior to the beginning of the trial. Additionally, patients were required to test negative for tuberculosis at entry and annually throughout the study.
Participants were randomized into three equal arms to receive either oral tofacitinib (Xeljanz, Pfizer) 5 mg, oral tofacitinib 10 mg — both twice daily — or a subcutaneous TNF inhibitor — adalimumab (Humira, AbbVie) — every 2 weeks. The study was updated in early 2019 to reduce the 10 mg tofacitinib patients to 5 mg after an increase in adverse events and mortality.
This analysis included evaluation of all infections, serious infection events of fatal and non-fatal varieties, nonserious infections, herpes zoster and adjudicated opportunistic infections, including TB.
According to the researchers, he incidence and HR for all infections, including serious and nonserious infections, were higher in the groups that received tofacitinib compared with those who received adalimumab.
The HRs for serious infection events were 1.17 (95% CI, 0.92-1.5) for patients receiving tofacitinib 5 mg and 1.48 (95% CI, 1.17-1.87) for patients receiving tofacitinib 10 mg, compared with those who received the TNF inhibitor.
According to the researchers, hazard and incidence rates of infections and serious infection events were “more pronounced” in patients aged 65 years and older, compared with patients aged 50 to 64 years. In addition, the chances of serious infection events occurring increased at month 18 for patients receiving tofacitinib 5 mg, and prior to 6 months for patients receiving tofacitinib 10 mg. Factors most predictive of serious infection events were age, opioid use at baseline, a history of chronic lung diseases and time-dependent oral corticosteroid use.
“Results of ORAL Surveillance showed dose-dependent increases in all infections, [serious infection events (SIEs)] and NSIs with tofacitinib versus TNFi in patients aged 50 years with 1 additional CV risk factor,” Balanescu and colleagues wrote. “The risk for all infections and SIEs increased with both tofacitinib doses versus TNFi, regardless of age, although an elevated risk with tofacitinib 10mg two times per day versus 5mg two times per day and TNFi was most pronounced in patients aged 65 vs 50– < 65 years.”
References:
- Bechman K, et al. Arthritis Rheumatol. 2015;doi:10.1016/S0140-6736(14)61704-9.
- Listing J, et al. Rheumatology. 2013;doi:10.1093/rheumatology/kes305.
- Singh JA, et al. Lancet. 20156;doi: 10.1016/S0140-6736(14)61704-9.
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