Frequency of Monotherapy versus Combination Therapy in Reported Cases of Infections Occurring in the Setting of Biologic Agents

Abstract

The purpose of this work was to determine the frequency with which concomitant immunosuppressive medications were used in a systemic review of reported cases of infection occurring in the setting of biologic therapy. A Pub Med search was conducted using the term “infection” combined with “biologic” and specific biologic drug names to identify case reports and case series written in English documenting patients who were diagnosed with an infection while being treated with a biologic agent. Demographic information, biologic medication, treatment indication, and patient outcomes, as well as information regarding the use of concomitant immunosuppressive therapies, were recorded. A total of 246 patients from 148 case reports and 20 case series met inclusion criteria and were evaluated. Among reported cases of infection occurring in the setting of biologic therapy, 69.9% were being treated with ≥1 other immunosuppressive medication. Of patients receiving concomitant therapies, corticosteroids (56.4%) and methotrexate (53.5%) were taken most frequently. Bacteria composed the majority of infections in this review (57.7%) with nonmycobacteria implicated in 38.6% of cases and mycobacteria in 19.1% of patients. In this cohort, patients receiving tumor necrosis factor-α inhibitors with other immunosuppressive medications experienced 2.67 times more reported nonserious infections (outpatient management), 2.33 times more reported hospitalizations, and 2.75 times more deaths than patients receiving biologic monotherapy. Infection risk among patients on biologic therapy is significantly confounded by the widespread use of concomitant immunosuppressive medication(s) and may be overestimated, particularly for patients who take biologic drugs as monotherapy.