Tocilizumab increases risk of GI perforation in rheumatoid arthritis: BMJ
Sweden: Tocilizumab (Actemra) treatment versus TNF inhibitors in patients with rheumatoid arthritis (RA) doubles the risk of gastrointestinal perforations, suggests a recent study published in the BMJ journal RMD Open.
Compared to patients who do not have RA, RA patients are known to be at increased risk of gastrointestinal (GI) complications. Of these, GI perforations are rare but potentially lethal. It is however not clear whether these perforations are caused by inflammation or other RA processes, or rather by RA treatments.
Andrei Barbulescu, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden, and colleagues compared the incidence rates of GI perforations between RA patients and the general population, and between patients treated with tumor necrosis factor inhibitors (TNFi) and non-TNFi biologics.
This nationwide cohort study included a total of 63 532 RA patients, with 26 050 biological treatment episodes (TNFi, rituximab, abatacept or tocilizumab) and 76 304 general population controls. They were followed between 2009 and 2017 until the first outcome event.
The main outcome was hospitalization or death due to lower GI perforations, identified according to a prespecified list of ICD-10 (International Classification of Diseases, 10th revision) codes.
Key findings of the study include:
- The sex-standardised and age-standardised incidence rates of lower GI perforations were 1.1 events per 1000 person-years among general population controls, 1.6 among bionaïve patients and ranged from 1.8 (TNFi) to 4.5 (tocilizumab) among biologics-treated patients.
- After adjustment for glucocorticoid use, the risk in bionaïve, TNFi-treated, abatacept-treated or rituximab-treated patients with RA was no longer different from the general population, while for tocilizumab it remained significantly higher.
- Comparing tocilizumab to TNFi, the adjusted HR for lower GI perforations was 2.2, 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 RA," concluded the authors.
"Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study," is published in the journal RMD Open.