Tofacitinib linked to elevated infection risk in real-world study
medwireNews: Rheumatoid arthritis patients treated with tofacitinib in routine clinical practice have a higher risk for serious infections, including herpes zoster, than those given other biologic agents, researchers report.
Seoyoung Kim (Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA) and team used three US databases to investigate serious infection risk among 130,718 patients initiating treatment with either tofacitinib (n=6278) or one of seven biologic agents (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or tocilizumab; n=124,440) between 2012 and 2018.
In all, 3140 patients experienced the primary composite outcome of hospital admission for serious infection including bacterial, viral, or opportunistic infection over 100,790 person–years of follow-up, giving an incidence rate of 3.12 events per 100 person–years.
After propensity score-based inverse probability treatment weighting to adjust for potential confounders, patients treated with tofacitinib had a significant 41% higher risk for serious infection than those given etanercept, with incidence rates of 3.52 versus 2.32 events per 100 person–years.
Serious infection risk was numerically, but not significantly, higher among patients treated with tofacitinib versus those in the abatacept, golimumab, and tocilizumab groups, and was similar among individuals treated with the Janus kinase (JAK) inhibitor versus adalimumab or certolizumab pegol, say Kim and team.
Conversely, patients in the tofacitinib group had a numerically lower risk for serious infection compared with those in the infliximab group, but again the difference did not reach statistical significance.
Tofacitinib was associated with an approximate doubling in the risk for herpes zoster, with significant differences in incidence rates relative to all biologics. The rate of herpes zoster per 100 person–years was 3.72 in the tofacitinib group, and ranged from 1.65 to 2.15 in the biologic groups.
“These differences in the risk of serious infection should be carefully considered when deciding an appropriate [biologic] DMARD and [targeted synthetic] DMARD therapy for patients with rheumatoid arthritis,” write the researchers.
In a comment accompanying the research published in The Lancet Rheumatology, Ennio Giulio Favalli (Gaetano Pini-CTO Institute, Milan, Italy) notes that the observed infection rates were higher than those reported in a recent meta-analysis of phase 2 and 3 randomized controlled trials of tofacitinib.
Favalli says that this discrepancy “was expected,” because “many comorbidities associated with a higher infectious risk are considered criteria for exclusion” in randomized controlled trials, whereas the database analysis included patients from routine clinical practice.
“Therefore, the generalisability of the results to the overall rheumatoid arthritis population is one of the main strengths” of the study, he adds.
The commentator believes that the findings “reinforce the idea that a vaccination strategy should be applied in all patients at risk of herpes zoster infection,” as advocated by EULAR.
“From this perspective, the availability of a recombinant vaccine that does not require the temporary suspension or postponement of immunosuppressive therapy will make vaccination of candidates for JAK inhibitors more feasible in clinical practice,” he concludes.
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