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Comparative Harms of Biologic Therapies – Tb and All-Site Serious Infections

November 17 2014 8:20 PM ET via RheumReports RheumReports

During the "Hot Topics in RA" session at the ACR Monday morning, Dr. Will Dixon addressed the comparative harms of biologic therapies.


Early anti-TNF RCTs suggested a differential risk for tuberculoisis (Tb) with more cases reported with monoclonal antibodies than with etanercept. This was also observed in pharmacovigilance reports.

Subsequently, a review of the the British Society for Rheumatology Biologic Register (BSRBR) reported 40 cases of incident Tb. These cases were all found in patients treated with anti-TNF, whereas there were no cases of Tb in the DMARD controls. The findings from the BSRBR have now been confirmed in the Swedish (ARTIS) registry, which reported about a 3-fold increased risk of Tb with monoclonal antibodies vs. etanercept. Fortunately, screening for latent Tb has reduced this risk.

Dr. Dixon's review of the literature found no cases of Tb with rituximab or tocilizumab. He reported two controversial cases with abatacept. These biologics all appear to be safer in terms of Tb reactivation than infliximab.

Higher rates of Tb have been reported with golimumab and certolizumab, however, these medications were studied in populations where the background prevalence of Tb was higher.

There have been 7 reported cases of Tb with Tofacitinib.

All-Site Serious Infections

In a network meta-analysis combining all of the data for all biologics (Singh J et al, Lancet 2014 in press), the odds ratio (OR) of serious infection was 1.3 meaning a 30% increased risk with standard dose biologics vs. traditional DMARDs. This risk was lower for low-dose biologics (OR=0.93) whereas it was higher with high dose biologics (OR=1.9). This is helpful but what we really want to know is whether one of these biologics is safer than another.

Based on Dr. Dixon's review of the literature, his conclusions about the comparative risks of serious infection are as follows:

  • The risk with infliximab appears higher than with etanercept, adalimumab, abatacept, or rituximab. However, surveillance bias must be considered.
  • Although the overall risk with rituximab was lower than infliximab, it was actually higher in patients who were "high-risk" for infection and in those with low IgG levels.
  • Certolizumab has the highest risk of serious infection in clinical trials.

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Dr. Andy Thompson
Dr. Andy Thompson

Dr. Andy Thompson is an Associate Professor at Western University and founder of,, and

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