Does tocilizumab lead to intestinal perforation in patients with rheumatoid arthritis?

This study looked at the risk of developing lower intestinal perforations (tears) in patients with rheumatoid arthritis treated with tocilizumab (Actemra). The authors concluded that tocilizumab treatment increases the risk of lower intestinal perforations compared to other treatments.

One problem encountered by some patients with rheumatoid arthritis (RA) is lower intestinal perforations (LIPs). These are holes that develop in the wall of the intestine. LIPs can lead to severe abdominal pain, chills, nausea, fever and even death.

Treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs) are known to increase the risk of perforations in the gastrointestinal (GI) tract. It was thought that biological drugs such as tumor necrosis factor inhibitors (TNFi), such as adalimumab (Humira), would lower the risk of LIPs. However when these were taken in conjunction with GCs the risk was still increased.

Tocilizumab is a newer biological drug that was shown to increase the risk of GI perforations in clinical trials. The risk of developing GI perforations in patients treated with this drug outside of trials is not clear.

RA patients receiving tocilizumab, disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (Rheumatrex), TNFis, abatacept (Orencia) or rituximab (Rituxan) were included in this study. 13,310 patients were included in the analysis. The authors looked at the number of GI perforations associated with each treatment.

The number of GI perforations in patients receiving DMARDs, TNFi, abatacept and rituximab were all similar. Patients receiving tocilizumab showed significantly higher rates of LIPs. Tocilizumab-treated patients were 4.5 times more at risk of LIPs than patients receiving DMARDs.

Overall, higher age, use of GCs and NSAIDs and treatment with tocilizumab were all linked to higher rates of LIPs. 

Patients receiving treatment with tocilizumab are at a significantly higher risk of GI perforations than those on DMARDS, TNFi or other biologics. 

The exact dosages and length of use of NSAIDs may not have been correctly reported for all participants. Previous GI complications can also contribute to LIPs. These may also have been underreported by patients in this study.

Consult with your physician if you have any concerns regarding your gastrointestinal health.