Safety of tuberculosis preventive treatment among people receiving or about to initiate immunosuppressive medications: a systematic review and meta-analysis.

BACKGROUND

People receiving immunosuppressive medications are at increased risk of tuberculosis. Tuberculosis preventive treatment (TPT) can reduce risk, however its safety among these populations is uncertain. We conducted a meta-analysis to evaluate adverse events (AE) associated with TPT among people receiving or about to initiate immunosuppressive medications.

METHODS

We searched MEDLINE, Cochrane, Health Star, and EMBASE (1952-May 1, 2025), for studies reporting AE during TPT among people receiving or about to initiate immunosuppressives. We used random-effects generalized linear mixed models with Hartung-Knapp 95% confidence intervals to estimate our primary outcome: pooled proportion of AE-related discontinuation, stratified by TPT regimen.

RESULTS

We included 27 studies (3184 participants). Populations included biologics/steroids recipients and solid organ/hematopoietic transplant candidates/recipients. For the primary outcome (25 studies, 2802 participants), TPT regimens included 6-12-month mono-isoniazid regimens (1511 participants), 4-months mono-rifamycin regimens (228 participants), 3-month isoniazid-rifamycin combination regimens (990 participants), and 6-9-month fluoroquinolone-based regimens (73 participants). Only mono-isoniazid regimens were provided while receiving immunosuppressives. Pooled AE-related discontinuation was 5.3% (95% CI: 3.1-8.9%; I2=65.4%) for mono-isoniazid regimens, 4.4% (95% CI: 0.1-75.4%; I2=86.3%) for mono-rifamycin regimens, 2.0% (1.0-4.1%; I2=0.0%) for isoniazid-rifamycin combination regimens, and 6.9% (95% CI: 0-92.3%; I2=65.4%) for fluoroquinolone-based regimens. Proportions were similar when stratified by biologics/steroids and transplant populations.

CONCLUSION

Overall, AE-related TPT discontinuation was like the broader TPT literature. AE-related discontinuation of TPT was lowest with rifamycin-containing regimens, but these were only provided prior to initiating immunosuppressives. Data on the safety of non-isoniazid regimens among people receiving immunosuppressives are needed.