Comparative effectiveness and safety of imported and domestic immune checkpoint inhibitors in China: A systematic review and pairwise and network meta-analyses

Multiple brands of immune checkpoint inhibitors (ICIs), including domestic and imported agents, have been approved as front-line therapy in China. However, little is known about the difference in efficacy and safety of these agents of different origins. This study aims to systematically compare the difference between National Medical Products Administration (NMPA) approved domestic and imported ICIs regarding their efficacy, safety, and price. We systematically searched PubMed, Embase, and Cochrane Central, from inception to July 1st, 2023, for phase III trials evaluating ICIs as first- or second-line settings that have available hazard ratio (HR) for Asians or non-Asians. Studies of domestic and imported ICIs were screened and paired by the matching clinical characteristics as mirror groups. The primary endpoint was to assess the difference in efficacy between domestic and imported ICIs regarding overall survival. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Heterogeneity was assessed by I2 statistics. Monthly treatment costs for each drug were calculated based on dosing information on National Medical Products Administration (NMPA) label and prices extracted from INSIGHT database. The difference in monthly treatment costs was compared by unpaired T-test. The protocol is registered on PROSPERO, CRD42024580753. Overall, domestic ICIs exhibited better efficacy regarding overall survival (HR, 0.87; 95 % CI, 0.79–0.97; P < 0.05; I2 = 0) compared with imported agents. No difference was observed regarding benefits in progression free survival (HR, 0.95; 95 % CI, 0.82–1.09; P > 0.05; I2 = 0). Consistent results were obtained through frequentists and Bayesian approaches. The differences in safety; measured by relative risk of treatment-related adverse events (TARE) of any grade, TARE of grade 3 or higher, immune-related adverse events(irAE) of any grade, irAE of grade 3 or higher, discontinuation due to treatment, and death due to treatment; were also similar between domestic and imported ICIs. Moreover, in current Chinese market, the monthly treatment prices of domestic ICIs was statistically lower than that of imported ICIs (P < 0.01). Our research provides an essential reference of cost-effectiveness of ICIs manufactured in China for clinicians in routine practice of cancer care as well as public health authorities for decision making process. [Display omitted]