Comparative safety of generic versus brand calcineurin inhibitors in solid organ transplant patients: A systematic review and meta-analysis.

BACKGROUND

Although generic ciclosporin-A (CsA) and tacrolimus (TAC) have been used for the prophylaxis of organ rejection in transplant patients for decades, evidence in their safety profile compared to reference listed drugs (RLDs) in real-world transplant patients remains limited.

OBJECTIVES

To compare safety outcomes of generic CsA and TAC with the reference-listed drugs in solid organ transplant patients.

METHODS

We systematically searched MEDLINE, International Pharmaceutical Abstracts, PsycINFO, and Cumulative Index of Nursing and Allied Health Literature from inception until March 15, 2022, to select randomized and observational studies comparing safety profiles of generic versus brand CsA and TAC in de novo and/or stable solid organ transplant patients. Primary safety outcomes were changes in serum creatinine (Scr) and glomerular filtration rate (GFR). Secondary outcomes included incidences of infection, hypertension, diabetes, other serious adverse events (AEs), hospitalization, and death. Mean difference (MD) and relative risk (RR) with 95% confidence intervals (CIs) were calculated using random-effects meta-analyses.

RESULTS

Of 2612 publications identified, 32 studies met inclusion criteria. Seventeen studies had a moderate risk of bias. Scr was statistically significantly lower in patients using generic CsA compared to brand at 1 month (MD = -0.07; 95% CI: -0.11, -0.04), while there were no statistically significant differences at 4 months, 6 months, and 12 months. No differences were detected in Scr (MD = -0.04; 95% CI: -0.13, 0.04) and estimated GFR (MD = -2.06; 95% CI: -8.89, 4.77) between patients using generic and brand TAC at 6 months. No statistically significant differences between generic CsA and TAC with their RLDs were observed for secondary outcomes.

CONCLUSION

Findings support similarity in safety outcomes between generic and brand CsA and TAC in real-world solid organ transplant patients.