Can Biologic DMARDs Protect Against Sepsis?

SAN FRANCISCO, CA—Biologic DMARDs (bDMARDs) confer a protective effect in patients with rheumatoid arthritis, lowering risk of developing sepsis as well as reducing mortality after serious infection and sepsis, according to results from a German registry presented at the 2015 ACR/ARHP Annual Meeting.

Adrian Richter, MSc, from the German Rheumatism Research Center, Berlin, Germany, also noted that discontinuation of bDMARDs shows that their protective effects recede in a time-dependent manner.

Inhibition of tumor necrosis factor-alpha (TNF-α) was believed to be the mechanism of action in the treatment of sepsis. However, randomized controlled trials have not demonstrated a survival benefit with the use of TNF inhibitors in patients diagnosed with sepsis. 

Richter and colleagues examined the outcomes of 1,017 serious infections in 859 patients enrolled in the German biologics registry RABBIT (Rheumatoid Arthritis oBservation of BIologic Therapy). They investigated the following outcomes: (1) no complication of serious infection, (2) sepsis following serious infection (≤30 days), and (3) death after serious infection (≤90 days). The risks of sepsis and death were adjusted for age at time of infection, sex, physical function, comorbid heart failure or renal disease, glucocorticoid dose, and DMARDs; bDMARDs were categorized as either TNF-inhibitors or others. 

The bDMARDs included were adalimumab, etanercept, rituximab, tocilizumab, infliximab, abatacept, certolizumab, golimiumab, and anakinra.

Results showed that 137 patients with a serious infection developed sepsis; 53 patients died, and 827 were cured.

The odds ratio of sepsis was significantly higher in older patients and in those with chronic renal disease. 

Patients exposed to bDMARDs who were in better physical function (odds ratio [OR] 0.92; 95% CI: 0.84–1.00) had significantly lower risk of developing sepsis. Risk factors such as older age, high-dose glucocorticoid, and heart failure increased the risk for serious infection, whereas treatment with bDMARDs (OR 0.48; 95% CI: 0.24–0.95 [TNF inhibitors], OR 0.16; 95% CI: 0.05–0.54 [other bDMARDs]) and better physical function (OR 0.86; 95% CI: 0.76–0.98) lowered the risk of death after a serious infection. 

Richter concluded that further investigation is needed to determine whether the serious infections are bacterial or viral in nature and whether the protective effects can be attributed to individual bDMARDs.

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