Why & How Our Biologic Drug Discussion with Patients Should Evolve

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Boxed warnings report on several opportunistic infections that have occurred in RA patients taking biologics. Certainly, such infections have also occurred in RA and non-RA patients not taking biologics. To determine the incidence of these opportunistic infections, Rutherford et al. analyzed data from a British registry on RA patients taking biologics and found the incidence to be low, at slightly over one case per 1,000 patient-years.¹⁶ Their analysis also indicated the incidence per calendar year had decreased from eight per 1,000 in 2002 to less than one per 1,000 in 2015—during the biologic era.

In a recent systematic literature review of qualified studies on comparative safety of biologics vs. csDMARDs, the composite literature suggested a slightly higher risk for serious infection with biologics over csDMARDs, although the authors pointed out the more recent studies with low bias found no difference.¹⁷ This is relevant to the safety of anti-TNF biologics, because Lacaille et al. showed the use of csDMARDs does not increase the risk of infection in RA, and a study by Smitten et al. demonstrated the risk of hospitalized infections was diminished in patients taking the csDMARDs methotrexate and hydroxychloroquine compared with patients on no treatment for RA.^12,18

Suspending csDMARDs around the time of elective surgery is no longer recommended because no difference in perioperative infections, wound healing or other complications can be demonstrated in comparison with continuing the drugs.¹⁹ Although consensus on the abstinence intervals for biologic drugs for elective surgeries is still formulating, in a retrospective analysis, George et al. found that Medicare patients who received infliximab less than four weeks before hip or knee arthroplasty were not at a higher risk of short- or long-term serious infection than those who had biologics withheld for longer time periods.^3,20

Similarly, the CDC no longer recommends live vaccines be avoided in patients on csDMARDs. Jinno et al. found that hospitalizations for pneumonias and opportunistic infections in people with RA decreased between 1993 and 2013, although the incidence of sepsis rose, likely due, as in other studies, to sensitivity of coding for sepsis rather than actual increase in occurrence of sepsis.²¹

Lastly, also from 2017, Accortt et al. demonstrated from the Consortium of Rheumatology Researchers of North America (CORRONA), a large registry of rheumatoid arthritis patients, that low disease activity and remission rates in patients with RA are associated with lower serious infection rates.

Overall, biologics do not increase mortality.²² Rather, biologic agents for RA, including anti-TNF agents, are correlated with reduced all-cause mortality.²³