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Patients with rheumatoid arthritis (RA) who initiated therapy with abatacept (Orencia) had a lower risk of being hospitalized for infection compared with those initiating treatment with a tumor necrosis factor (TNF) inhibitor, an examination of claims data found.

The overall incidence rate for any hospitalized infection was 36.7/1,000 person-years (95% CI 31.8-42.3) for abatacept initiators vs 47.4 per 1,000 person-years (95% CI 41.5-54.1) for anti-TNF initiators, according to Seoyoung C. Kim, MD, ScD, and colleagues from Brigham and Women's Hospital and Harvard Medical School in Boston.

Accordingly, the hazard ratio (HR) for a hospitalized infection among patients being treated with abatacept was 0.78 (95% CI 0.64-0.95), the researchers reported online in .

Patients with RA are at increased risk of serious infections, which is further heightened by the use of today's powerful immunosuppressive therapies.

The efficacy of TNF inhibitors and abatacept have been shown to be comparable, but the associated risk of infection is uncertain, with previous analyses having had conflicting results.

Therefore, to address the question as to which treatment option may be safer with regard to infections, Kim's group analyzed data from the Truven MarketScan database for the years 2006 to 2015, identifying new users of abatacept or the TNF inhibitors adalimumab (Humira), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade).

Initiators of abatacept were allowed to have had previous exposure to TNF inhibitors, and initiators of TNF inhibitors were permitted to have had previous use of abatacept.

Participants were propensity score-matched for multiple covariates that could influence infection risk, including demographics, comorbidities, and use of other medications. After this matching, there were 11,248 pairs of patients initiating abatacept or TNF inhibitors. Mean age was 55, and 84% were women.

Steroid use in the 30 days prior to study enrollment was common in both groups (44% for abatacept, 42% for TNF inhibitors). A total of 58% of the abatacept group had previously used TNF inhibitors, whereas only 4% of the TNF inhibitor group had prior exposure to abatacept.

In a sensitivity analysis that compared the risk between abatacept and the three most commonly used TNF inhibitors, the hazard ratio remained lower for abatacept vs infliximab (HR 0.63, 95% CI 0.47-0.85), although not for adalimumab (HR 0.78, 95% CI 0.57-1.06) or etanercept (HR 1.19, 95% CI 95% CI 0.92-1.53).

In secondary analyses that looked at specific types of infection, only respiratory tract infections were lower with abatacept (HR 0.71, 95% CI 0.52-0.99). No differences were seen for infections of the gastrointestinal, cardiac, or genitourinary systems, or for bacterial infections or herpes zoster specifically.

An additional sensitivity analysis that included only patients who had never received either of the treatments previously also found no difference in risk (HR 0.87, 95% CI 0.68-1.11).

Potential reasons for the observed differences in risks among the individual TNF inhibitors include a higher peak concentration of infliximab, which is given by infusion, whereas adalimumab and etanercept are administered by subcutaneous injection. In addition, the steady state drug level of etanercept is lower and it binds only circulating TNF, while infliximab also can bind to TNF on cell membranes.

As to the lower risk of infection with abatacept, the reason is "unknown but may potentially be due to the fact that abatacept indirectly blocks T-cell costimulation rather than the mechanism of directly inhibiting cytokines for TNF inhibitors," Kim and colleagues wrote.

"In this large nationwide cohort of RA patients in the U.S. initiating abatacept or a TNF inhibitor as a first- or second-line biologic therapy, we found a lower risk of any hospitalized infections associated with abatacept versus TNF inhibitors, particularly in comparison to infliximab, suggesting that RA patients with specific concerns about infections may benefit from use of abatacept compared to TNF inhibitors," the researchers concluded.

A limitation of the study, they said, was the lack of information in the database about disease activity and socioeconomic status.

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