Introduction: Certolizumab pegol (CZP), is currently approved for treatment of Crohn’s disease (CD), rheumatoid arthritis (RA), axial spondyloarthritis (AS) and psoriatic arthritis (PA) [1]. To our knowledge, no systematic review and meta-analysis, evaluating the overall safety profile of CZP in patients with immune-mediated inflammatory diseases (IMIDs), have been performed. Aim: To assess the adverse event (AE) patterns of CZP versus control in patients with IMIDs, focusing on AEs, serious AEs (SAEs), adverse drug reactions (ADRs), infectious SAEs, injection site reactions, neoplasms and tubercolosis. Methods: A systematic literature search was performed using PubMed/ MEDLINE, EMBASE, Cochrane Library and FDA database for clinical trials up to March 2014.Articles reporting randomized controlled trials (RCTs), evaluating the safety profile of CZP in patients with CD, RA, AS, PA or psoriasis, were selected for the meta-analysis. The following data were extracted: number and related incidence of patients who experienced overall AEs and SAEs, ADRs, withdrawals due to AEs, fatal AEs, infectious AEs, infectious SAEs, upper respiratory tract infections, injection site reactions, neoplasms (including malignant and benign lesions) and tubercolosis. Results were calculated as pooled risk ratios. Results: A total of 2023 references were identified and a total of 18 RCTs, involving 6992 participants (4,589 randomized to CZP 200 or 400 mg, and 2,403 to control), were included. The main findings for the pooled risk ratios in CZP-treated versus control patients were: overall AEs 1.07 (95 % CI 1.03–1.10), overall SAEs 1.58 (95 % CI 1.31–1.92), overall ADRs 1.20 (95 % CI 1.05–1.38), infectious SAEs 2.14 (95 % CI 1.34–3.43), injection site reactions 2.01 (95 % CI 0.95–4.29), neoplasms 1.18 (95 % CI 0.59–2.39) and tubercolosis 2.90 (95 % CI 0.73–11.43). Risk ratios estimates for other safety data extracted in our study were: withdrawals due to AEs 1.19 (95 % CI 0.96–1.47), fatal AEs 2.08 (95 % CI 0.83–5.17), infectious AEs 1.21 (95 % CI 1.09–1.34) and upper respiratory tract infections 1.33 (95 % CI 1.15–1.53). Conclusion: Safety data on CZP, largely originated from pre-authorization trials, suggest a favorable tolerability profile, with infections being the most common AEs. Large observational studies or the analysis of data from national registries of ADRs are needed, particularly for detecting rare AEs (such as neoplasms), that might occur after long-term exposures to CZP.

Update of Certolizumab Pegol Safety Profile: A Systematic Review and Meta-Analysis

Mantarro, S;Blandizzi, C;Ruggiero, E;Convertino, I;Antonioli, L;Fornai, M;Tuccori, M
2014-01-01

Abstract

Introduction: Certolizumab pegol (CZP), is currently approved for treatment of Crohn’s disease (CD), rheumatoid arthritis (RA), axial spondyloarthritis (AS) and psoriatic arthritis (PA) [1]. To our knowledge, no systematic review and meta-analysis, evaluating the overall safety profile of CZP in patients with immune-mediated inflammatory diseases (IMIDs), have been performed. Aim: To assess the adverse event (AE) patterns of CZP versus control in patients with IMIDs, focusing on AEs, serious AEs (SAEs), adverse drug reactions (ADRs), infectious SAEs, injection site reactions, neoplasms and tubercolosis. Methods: A systematic literature search was performed using PubMed/ MEDLINE, EMBASE, Cochrane Library and FDA database for clinical trials up to March 2014.Articles reporting randomized controlled trials (RCTs), evaluating the safety profile of CZP in patients with CD, RA, AS, PA or psoriasis, were selected for the meta-analysis. The following data were extracted: number and related incidence of patients who experienced overall AEs and SAEs, ADRs, withdrawals due to AEs, fatal AEs, infectious AEs, infectious SAEs, upper respiratory tract infections, injection site reactions, neoplasms (including malignant and benign lesions) and tubercolosis. Results were calculated as pooled risk ratios. Results: A total of 2023 references were identified and a total of 18 RCTs, involving 6992 participants (4,589 randomized to CZP 200 or 400 mg, and 2,403 to control), were included. The main findings for the pooled risk ratios in CZP-treated versus control patients were: overall AEs 1.07 (95 % CI 1.03–1.10), overall SAEs 1.58 (95 % CI 1.31–1.92), overall ADRs 1.20 (95 % CI 1.05–1.38), infectious SAEs 2.14 (95 % CI 1.34–3.43), injection site reactions 2.01 (95 % CI 0.95–4.29), neoplasms 1.18 (95 % CI 0.59–2.39) and tubercolosis 2.90 (95 % CI 0.73–11.43). Risk ratios estimates for other safety data extracted in our study were: withdrawals due to AEs 1.19 (95 % CI 0.96–1.47), fatal AEs 2.08 (95 % CI 0.83–5.17), infectious AEs 1.21 (95 % CI 1.09–1.34) and upper respiratory tract infections 1.33 (95 % CI 1.15–1.53). Conclusion: Safety data on CZP, largely originated from pre-authorization trials, suggest a favorable tolerability profile, with infections being the most common AEs. Large observational studies or the analysis of data from national registries of ADRs are needed, particularly for detecting rare AEs (such as neoplasms), that might occur after long-term exposures to CZP.
https://link.springer.com/article/10.1007/s40264-014-0208-1
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1101240
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