Coccidioidomycosis Screening Benefits TNFi Therapy Recipients

Screening of asymptomatic coccidioidomycosis within a Coccidioides-endemic area allowed for identification and management of asymptomatic coccidioidomycosis before patients began tumor necrosis factor-α inhibitor (TNFi) therapy, according to a study recently published in Clinical Infectious Diseases.

TNFi therapies have advanced the treatment of numerous inflammatory diseases because they act by impairing select functions of cellular immunity. However, by doing so, these medications increase the risk for mycobacterial and certain fungal infections, including coccidioidomycosis. Coccidioidomycosis is an infection caused by the dimorphic fungus Coccidioides, which is primarily endemic to southern Arizona, the southern and central valleys of California, southwestern New Mexico, and west Texas in the United States. 

Coccidioidomycosis commonly presents as a self-limited pulmonary infection. Control of coccidioidomycosis depends on intact cellular immunity. Therefore, continued study of the relationship between TNFi medications and coccidioidomycosis is a high priority in Coccidioides-endemic areas. However, little information exists regarding coccidioidomycosis infection in the setting of TNFi therapy. In an effort to fill this research gap, the current study compared the outcomes of TNFi recipients screened for asymptomatic coccidioidomycosis with those of unscreened persons to compare development of symptomatic coccidioidomycosis and to describe outcomes for patients with abnormal coccidioidal screening.

Individuals receiving a TNFi for dermatologic, rheumatologic, or gastroenterologic diagnoses from September 2010 to September 2016 were identified through electronic health records. A total of 2793 patients were prescribed a TNFi. Patients were then further categorized by whether they had undergone coccidioidal serologic testing for screening or diagnostic purposes. The utility of coccidioidal screening was assessed by comparing the rate of development of symptomatic coccidioidomycosis in TNFi recipients who were screened vs those who were not screened for coccidioidomycosis.

Among the 925 individuals who underwent screening for coccidioidomycosis, 5.7% had abnormal coccidioidal serologic tests, of whom 3.9% met the definition for coccidioidomycosis. In addition, 19% of individuals with abnormal serology were identified as having probable coccidioidomycosis, 31% were identified as having possible coccidioidomycosis, and 50% were asymptomatic. Of the 1025 unscreened patients, coccidioidomycosis developed in 3% compared with 1% of screened patients.

Further, a multivariate logistic regression analysis did not identify increased risk among the screened or unscreened cohort regarding age (P =.90), non-white race/ethnicity (P =.16), or underlying inflammatory disease (P =.98). Although, among the screened and unscreened cohorts, women were more likely to contract symptomatic coccidioidomycosis (P =.004). The absolute risk for coccidioidomycosis in the screened population was 1.3% and the absolute risk in the unscreened population was 3.4%. The absolute risk reduction of screening was 2.1% and the number needed to screen to avoid 1 symptomatic case of coccidioidomycosis was 48. This suggests that screening for coccidioidomycosis, followed by assessing and treating prophylactically is statistically and clinically significant for patients beginning or continuing TNFi treatment within an endemic area.

Overall, the study authors conclude that, “[T]he mounting evidence demonstrating that patients receiving TNFi therapy who develop symptomatic coccidioidomycosis have high rates of hospitalization, disseminated disease, and death suggests that identifying coccidioidomycosis in asymptomatic TNFi recipients is important to prevent poor outcomes.”

Reference

Choi K, Deval N, Vyas A, Moran C, et al. The utility of screening for coccidioidomycosis in recipients of inhibitors of tumor necrosis factor-α. [published online August 2, 2018] Clin Infect Dis. doi: 10.1093/cid/ciy620