Soohyun Lee1, Heeyoung Lee2, EunYoung Kim3. 1. Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, 84, Heukseokro, Dongjak-gu, Seoul, 156-756, South Korea. 2. College of Pharmacy, Gachon University, Inchon, South Korea. 3. Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, 84, Heukseokro, Dongjak-gu, Seoul, 156-756, South Korea. eykimjcb777@cau.ac.kr.
Abstract
BACKGROUND: Rituximab is a biologic medicine widely used for the treatment of autoimmune diseases and lymphoma. Several biosimilars of rituximab have been developed and marketed with the expiration of the originator rituximab's patent; thus, systematic combination and analysis of the latest data on the efficacy and safety of biosimilars and the demonstration of the interchangeability of biosimilar agents are required. OBJECTIVE: The objective of this study was to collate available data from head-to-head randomized controlled trials (RCTs) and evaluate the efficacy and safety of biosimilar rituximab compared with the reference drug in patients with rheumatoid arthritis (RA) and non-Hodgkin's lymphoma (NHL). METHODS: The PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched to identify head-to-head RCTs that directly compare the efficacy and safety of biosimilar rituximab and its originator. The efficacy outcome for RA was the American College of Rheumatology (ACR) response rates and the outcome for NHL was the response rate. The occurrence of adverse events (AEs) and anti-drug antibodies (ADAs) were evaluated for the safety outcome. Data on the pharmacokinetic profile were also included as a secondary outcome. RESULTS: Eleven head-to-head RCTs with 3163 patients were included (1744 patients with RA and 1419 patients with NHL). Biosimilars of rituximab showed similar efficacy in the clinical response in both RA and NHL. The pooled risk ratio (RR) of the ACR 20% response rate (ACR20) response in patients with RA at weeks 24 and 48 was 0.99 (p = 0.70, 95% confidence interval [CI] 0.92-1.06) and 1.04 (p = 0.73, 95% CI 0.83-1.31), respectively. The pooled RR of the overall response at week 24 in NHL patients was 1.02 (p = 0.31, 95% CI 0.98-1.07). No significant differences were found in the formation of ADAs (RR 0.86, p = 0.20, 95% CI 0.68-1.08) or AEs (RR 1.04, p = 0.30, 95% CI 0.97-1.12). CONCLUSION: This systematic review and conventional meta-analysis demonstrated the overall similarity of the long-term efficacy and safety of biosimilar rituximab to those of originator rituximab in RA and NHL patients by combining direct evidence from head-to-head trials. PROSPERO registration No. CRD42019125138.
BACKGROUND:Rituximab is a biologic medicine widely used for the treatment of autoimmune diseases and lymphoma. Several biosimilars of rituximab have been developed and marketed with the expiration of the originator rituximab's patent; thus, systematic combination and analysis of the latest data on the efficacy and safety of biosimilars and the demonstration of the interchangeability of biosimilar agents are required. OBJECTIVE: The objective of this study was to collate available data from head-to-head randomized controlled trials (RCTs) and evaluate the efficacy and safety of biosimilar rituximab compared with the reference drug in patients with rheumatoid arthritis (RA) and non-Hodgkin's lymphoma (NHL). METHODS: The PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched to identify head-to-head RCTs that directly compare the efficacy and safety of biosimilar rituximab and its originator. The efficacy outcome for RA was the American College of Rheumatology (ACR) response rates and the outcome for NHL was the response rate. The occurrence of adverse events (AEs) and anti-drug antibodies (ADAs) were evaluated for the safety outcome. Data on the pharmacokinetic profile were also included as a secondary outcome. RESULTS: Eleven head-to-head RCTs with 3163 patients were included (1744 patients with RA and 1419 patients with NHL). Biosimilars of rituximab showed similar efficacy in the clinical response in both RA and NHL. The pooled risk ratio (RR) of the ACR 20% response rate (ACR20) response in patients with RA at weeks 24 and 48 was 0.99 (p = 0.70, 95% confidence interval [CI] 0.92-1.06) and 1.04 (p = 0.73, 95% CI 0.83-1.31), respectively. The pooled RR of the overall response at week 24 in NHLpatients was 1.02 (p = 0.31, 95% CI 0.98-1.07). No significant differences were found in the formation of ADAs (RR 0.86, p = 0.20, 95% CI 0.68-1.08) or AEs (RR 1.04, p = 0.30, 95% CI 0.97-1.12). CONCLUSION: This systematic review and conventional meta-analysis demonstrated the overall similarity of the long-term efficacy and safety of biosimilar rituximab to those of originator rituximab in RA and NHLpatients by combining direct evidence from head-to-head trials. PROSPERO registration No. CRD42019125138.