Biological disease-modifying anti-rheumatic drugs appear to more effectively reduce the risk of sepsis after serious infection in patients with rheumatoid arthritis (RA) than conventional drugs of this nature, researchers reported, based on a study of outcomes in RA patients.
This finding is important, because disease-modifying therapies used to treat RA — called tumor necrosis factor-alpha inhibitor therapies or TNFi — are known to increase a person’s risk of septic arthritis, which, like all types of sepsis, can be life-threatening.
The study, “Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis,” was published in the Annals of the Rheumatic Disease.
Biologic disease-modifying antirheumatic drugs (bDMARDs) can work as TNFis by targeting a protein called tumor necrosis factor (which, in excess, causes inflammation in joints). As such, bDMARDs are used in the routine care of moderate to severe RA after failure of conventional synthetic (cs)DMARDs. Due to their immunosuppressive effect, however, bDMARDs increase the risk of serious infections in RA patients, already at risk of infection due to the nature of their disease and its progression, complications of disease-related joint surgeries and impaired physical function.
Adrian Richter, with the Deutsches Rheuma-Forschungszentrum Berlin, and colleagues investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on outcomes of serious infection in 947 patients with rheumatoid arthritis.
Researchers evaluated the patients at baseline and again at three months, six months and every subsequent six months for the next five to 10 years. Outcomes observed included recovery with no complications, sepsis following a serious infection, and death after serious infection without sepsis.
According to their analysis, 135 patients developed sepsis within 30 days after a serious infection, and 85 of these patients died. Another 53 patients also died within 90 days of a serious infection, but were not seen to have sepsis. The results also revealed that the risk of developing sepsis increased with age, and was higher in RA patients with chronic renal disease.
Compared with patients who had been using csDMARDs, however, the risk of sepsis and death was significantly lower in those who had been exposed to bDMARDs at the time of a serious infection.
Researchers also found that advanced age, higher use of glucocorticoids, and heart failure were all risk factors for deadly infections.
“In conclusion, this study suggests that patients exposed to bDMARDs at the time of [serious infection] have a reduced risk of sepsis and mortality. The effective immunosuppression via bDMARDs may prevent an unregulated host response to [serious infection] and the development of sepsis. Discontinuation of bDMARDs seems to shift the risk from an increased susceptibility to [serious infection] to more severe outcomes,” the researchers wrote.
Further study is needed to confirm these findings, they said, noting that “we cannot conclude from our study that bDMARDs should be continued in case of [a serious infection] since this is the first study showing these results. They have to be confirmed … before any clinical consequences can be drawn.”