Background/Purpose:

Gastrointestinal (GI) perforations occur more often than expected in patients with RA. Reports indicate that tocilizumab may be associated with an increased risk of GI perforations compared to synthetic DMARDs (1) or to TNF inhibitors (TNFi) (2). Replications are needed, and there is little data on other biologic DMARDs. In this analysis, we compare GI perforation rates among RA patients exposed to rituximab, abatacept, tocilizumab, or TNFi.

Methods:

In this register-based cohort study we included all Swedish RA patients, with follow-up from 2010 to 2016. All initiations of treatment with TNFi, rituximab, abatacept, or tocilizumab were extracted from the Swedish rheumatology register (SRQ); each patient could contribute to several exposure cohorts. Follow-up under each exposure episode ended with a GI perforation event or at censoring by emigration, death, treatment switch or discontinuation, or end of study period. GI perforations were identified in the Swedish National Patient Register as any inpatient or outpatient diagnosis with an International Statistical Classification of Diseases and Related Health Problems (ICD) 10 code from a predefined list. Crude incidence rates were tabulated for each treatment cohort and relative effects were estimated as adjusted hazard ratios (HR) in multivariable Cox regressions, conditioning on baseline characteristics measured at the start of each episode (demographic, disease activity, co-medication, disease history).

Results:

We found some evidence for outcome relevant channeling, with patients starting abatacept or rituximab more often having a history of diverticular disease or GI perforation, and some differences in age and co-medication (Table 1). Table 2 presents observed person-time, number of events (95% of which were lower GI perforations), crude rates and adjusted comparisons. The crude GI perforation rate was lowest in the TNFi, and highest in the abatacept cohort. None of the adjusted comparisons of each non-TNFi biologic with TNFi biologics yielded hazard ratios significantly different from 1. 

Conclusion:

We could not replicate an increased rate of GI perforations for tocilizumab. Taking measured channeling of treatment into account, none of the non-TNFi biologics showed an increased risk compared to TNFi biologics. Effects of residual or unmeasured factors cannot be excluded.

References:

1. Strangfeld A, et al. Ann Rheum Dis 2017;76:504–510.

2. Xie F, et al. Arthritis Rheumatol 2016;68:2612–2617.