Tocilizumab May Be Associated With Increased GI Ruptures in RA

Swedish researchers writing in RMD Open report that tocilizumab may be associated with a higher risk of lower gastrointestinal perforations in rheumatoid arthritis patients as compared patients who took other biologics.

Rheumatoid arthrits patients are at greater risk of gastrointestinal complications, such as bowel inflammation, infections and perforations. And although perforations are rare, they can be lethal. How they occur remains a mystery. Experts suspect they occur as a result of inflammation associated with rheumatoid arthritis or possibly due to treatments used for rheumatoid arthritis. It is known that glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) are associated with the development of intestinal perforations. And, although the use of some biologics has been linked to an increase in the incidence of intestinal perforations in some rheumatoid arthritis cases, the extent to which biologic DMARDs may contribute to this problem is unknown.

In this study, Dr. Andrei Barbulescu of Karolinska Institute in Stockholm, conducted a nationwide cohort study in which he and his colleagues comapared the incidence rates of gastrointestinal perforations between patients with rheumatoid arthritis and the general population, and then between rheumatoid arthritis patients treated with tumour necrosis factor inhibitors (TNFi) and non-TNFi biologics.

The study included 63,532 rheumatoid arthritis patients who were treated with TNFi, rituximab, abatacept or tocilizumab biologics. The patients, and 76,304 controls, were followed for eight years between 2017 and 2009 or until the first outcome event. The main outcome was hospitalization or death due to lower GI perforations.

The incidence rates of lower GI perforations were 1.1 (95% CI 1.0 to 1.3) events per 1,000 person-years among general population controls compared to 1.6 (1.5–1.7) among biologic naive patients and ranged from 1.8 (1.4–3.6) (TNFi) to 4.5 (2.7–10.4) (tocilizumab) among biologics-treated patients. After adjustment for glucocorticoid use, the risk in bionaïve, TNFi-treated, abatacept-treated or rituximab-treated patients with rheumatoid arthritis was no longer different from the general population, while for tocilizumab it remained significantly higher. Comparing tocilizumab to TNFi, the adjusted hazard ration (HR) for lower GI perforations was 2.2 (1.3–3.8), corresponding to one additional GI perforation per 451 patient-years treated with tocilizumab instead of TNFi.

"Tocilizumab was associated with a higher risk of lower GI perforations compared with alternative biologics. In absolute numbers, the risk remained low on all biologics commonly used to treat RA, but the accumulated evidence across settings and outcome definitions supports that this risk should be considered in treatment guidelines for rheumatoid arthritis," the authors wrote.

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REFERENCE

Barbulescu A, Delcoigne B, Askling J, et al. Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study. RMD Open 2020;6:e001201. doi: 10.1136/rmdopen-2020-001201