Is there a greater risk of serious infection with tumor necrosis factor inhibitors for rheumatoid arthritis?

This study investigated the risk of serious infections with tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA).

They found no difference in serious infection risk with TNFi treatment compared to triple therapy.

Rheumatoid arthritis (RA) is a chronic disease. It is caused by excessive inflammation that causes pain and swelling in the joints. RA is treated with disease-modifying drugs anti-rheumatic (DMARDs). Conventional DMARDs (csDMARDs) are the first-line treatment for RA. Methotrexate (MTX; Otrexup) is a csDMARD. MTX targets a number of cellular pathways involved in inflammation. MTX can improve RA symptoms significantly. However, over time, patients may fail to respond to MTX. 

One option is to combine MTX with other csDMARDs. Triple therapy with MTX, hydroxychloroquine (HCQ; Plaquenil) and sulfasalazine (SSZ; Azulfidine) improves RA symptoms. Combining MTX with a tumor necrosis factor inhibitor (TNFi) is also effective in patients that no longer respond to MTX alone. TNFi drugs such as etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) are biological DMARDs (bDMARDs). Both of these options are effective. However, some studies suggest there may be a high risk of serious infection with TNFi treatment. It is unclear if the risk of serious infections is higher with TNFi + MTX compared to triple therapy.

This study included 46,693 patients who were prescribed RA medication for the first time. 1,388 patients had triple therapy (MTX + HCQ + SSZ). 45,305 patients received a TNFi + MTX (The TNF group). TNFi drugs included etanercept, infliximab, adalimumab, certolizumab (Cimzia) and golimumab (Simponi). The authors compared the rates of serious infections across the groups.

The risk of serious infection was not significantly different between the groups. The risk of bacterial or opportunistic infections was similar beween the groups. Herpes zoster infection rates were also similar between the groups. 

The authors concluded there was no difference in serious infection risk with TNFi treatment compared to triple therapy. 

This was a retrospective study meaning it was based on medical records. Information might have been missing. The number of patients with triple therapy was low compared to the TNF group. More studies are needed.