Higher Rates of Infection Reported in Tofacitinib vs TNFi in RA


Rates of serious and non-serious infection events were higher in patients receiving tofacitinib, 5 mg 2 times daily and 10 mg 2 times daily, when compared with TNFis.

Results from the ORAL Surveillance study reported that rates of infections were higher in patients with rheumatoid arthritis (RA) receiving tofacitinib, either 5 mg 2 times daily or 10 mg 2 times daily, versus tumor necrosis factor inhibitors (TNFi), according to a study published in Annals of the Rheumatic Diseases.1 Investigators noted that these outcomes may help to inform future treatment decisions.

Higher rates of infection reported in tofacitinib versus TNFi in patients with rheumatoid arthritis

“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,” investigators stated. “For example, the TNFi, etanercept, has been associated with reduced risk of infections versus other TNFi agentsand the Janus kinase (JAK) inhibitor, tofacitinib.”

The open-label, randomized controlled ORAL Surveillance (NCT02092467) trial evaluated patients with RA aged 50 years or older with 1 or more additional cardiovascular risk factor who were randomized 1:1:1 to receive either tofacitinib 5 mg twice daily, 10 mg twice daily, or a TNFi. Incidence rates (IRs) and hazard rations (HRs) were used to calculate infections, both overall and by age (50 to 65 years; 65 years and older). Infection probability was assessed by Kaplan-Meier estimates and Cox modelling identified risk factors of infection.

In total, 4362 patients were included in the study (tofacitinib 5 mg two times per day: n=1455; tofacitinib 10 mg two times per day: n=1456; TNFi: n=1451). Rates of serious infection events (SIEs), NSIs, and IRs/HRs (95% CI) for all infections were higher in the group receiving tofacitinib 5 mg 2 times daily and 10 mg 2 times daily when compared with TNFis.

Rates of SIEs in the tofacitinib 5 mg group were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87) in the tofacitinib 10 mg cohort. A total of 31 (2.1%) patients in the tofacitinib 5 mg group and 29 (2.0%) patients in the tofacitinib 10 mg group reported multiple SIEs, compared with 24 (1.7%) of patietns in the TNFi group. IRs/HRs for all infections and SIEs in patients receiving tofacitinib 10 mg twice daily were higher in patients aged older than 65 years.

The probability of SIE increased from month 18 for those receiving tofacitinib 5 mg twice daily and before month 6 in the tofacitinib 10 mg twice daily group compared with TNFi. However, NSI probability increased before month 6 for both tofacitinib cohorts.

The most common risk factors for SIEs included increased age, baseline opioid use, a history of chronic lung disease, and time-dependent oral corticosteroid use. NSI risk was increased for those with a history of chronic lung disease and/or infections, past smoking, female sex, and time-dependent Disease Activity Score in 28 joints (DAS-28), C-reactive protein (CRP) score.

As the ORAL Surveillance study was designed to evaluate non-inferiority of tofacitinib versus TNFi across safety endpoints, it did not compare infection events across treatment groups. Backward selection may have introduced a biased relationship between covariates and outcomes and the stability of this selection method may have affected the number of events. Results from the Cox regression analyses determining risk factors, such as heart failure, chronic renal disease, and inflammatory bowel disease, should be cautiously interpreted. Finally, risk of SIEs with tofacitinib versus etanercept or adalimumab, or etanercept versus adalimumab, could not be definitively concluded as TNFi drugs were confounded by geographical location.

“These findings from ORAL Surveillance may inform treatment decisions for patients with RA,” investigators concluded. “The higher risk of infections with tofacitinib versus TNFi, and risk factors identified for infections, should be considered as part of the shared decision-making between physicians and patients.”


Balanescu AR, Citera G, Pascual-Ramos V, et al. Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial [published online ahead of print, 2022 Aug 3]. Ann Rheum Dis. 2022;annrheumdis-2022-222405. doi:10.1136/ard-2022-222405

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