Efficacy and Safety in the Continued Treatment With a Biosimilar Drug in Patients Receiving Infliximab: A Systematic Review in the Context of Decision-Making From a Latin-American Country

Abstract

Introduction: Biological products, including infliximab (INF), are a therapeutic option for various medical conditions. In the Peruvian Social Security (EsSalud), infliximab is approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthropathy, ankylosing spondylitis, ulcerative colitis and Crohn’s disease (in cases refractory to conventional treatment). Biosimilars are a safe and effective alternative approved for these diseases in patients who start treatment with infliximab. Nevertheless, there are people in treatment with the biological reference product (BRP), in whom the continuing therapy with a biosimilar biological product (BBP) must be evaluated. Objectives: To synthesize the best available evidence, calculate a preliminary financial impact and conduct technical discussions about the interchangeability into biosimilar in patients receiving treatment with original infliximab for medical conditions approved in EsSalud. Methodology: We carried out a systematic review of controlled clinical trials. Primary search was performed in Pubmed- MEDLINE, SCOPUS, WOS, EMBASE, TRIPDATABASE, DARE, Cochrane Library, NICE, AHRQ, SMC, McMaster-PLUS, CADTH, and HSE until June-2018. We used the Cochrane Collaboration tool to assess the risk of bias. Also, we implemented a preliminary financial analysis about the impact of biosimilar introduction on institutional purchasing budget. Moreover, technical meetings with medical doctors specialized in rheumatology, gastroenterology and dermatology were held for discussing findings. Results: In primary search, 1136 records were identified, and 357 duplicates were removed. From 799 records, we excluded 765 after title and abstract evaluation. From 14 full-text appraised documents, we included five clinical trials in the risk of bias assessment: four studies evaluated CTP-13 and one tested SB2. Two double-blind clinical trials reported no differences in efficacy and safety profiles between maintenance group (INF/INF) and interchangeability group in all diseases included (INF/CTP-13) and rheumatoid arthritis (CTP13 and SB2). In the other three studies, open-label extension of primary clinical trials, no differences were founded in efficacy and safety profiles between CTP-13/CTP-13 and INF/CTP-13 groups. In financial analysis, the inclusion of biosimilars implied savings around S/7´642,780.00 (1USD=S/3.30) on purchasing budget of EsSalud. In technical meetings, beyond certain concerns, specialists agreed with the findings. Conclusions: Evidence from clinical trials support that there are no differences in efficacy or safety of continuing the treatment with Infliximab BRP or exchanging into its biosimilar in patients with medical conditions approved in EsSalud. Financial analysis shows that the biosimilar introduction produce savings in purchasing institutional budget. Therefore, based on cost-opportunity principle, exchanging into biosimilar in patients receiving the original Infliximab, is a valid therapeutic alternative in the Peruvian Social Security.

Infliximab switching from reference product to biosimilar: a review of evidence regarding the clinical efficacy, safety profile and immunogenicity

“…Previous literature reviews have evaluated safety and efficacy of switching to biosimilar infliximab from the reference product. Unlike our study, these reviews were limited to a single disease (IBD) 51 or setting 52 . Nonetheless, some limitations of this review should be noted.…”

Biologic Drugs for Rheumatoid Arthritis in the Context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment

“…Data on teratogenic effects of TNFi are limited and there is no strong evidence of potentially harmful effects, if used in preconception period [ 32 ]. Recent data and metanalysis suggest that biosimilar drugs are equal to their biooriginators, however, recent data have shown that treatment with biosimilar ADA, ETN and IFX might be associated with increased discontinuation rates due to medical and nonmedical issues, such as the nocebo effect [ 34 , 35 , 36 , 37 , 38 , 39 ]. Moreover, researchers from the UK suggest that nonmedical switch from biooriginal to biosimilar drug might involve higher costs from the medical system than continuation of the original drug [ 40 ].…”

Clinical Benefits of Switching from Original Infliximab to its Biosimilar (CT-P13) as a Potential TNF-α Inhibitor

“…63 The Peruvian Social Security (known as Es-Salud) reported biosimilarity between infliximab and CT-P13, and according to financial analysis determined it is a cost-effective decision. 64 In 2013, Park and colleagues 65 reported a Phase 1, doubleblind, parallel-group study of 22 and 30 weeks on 250 patients administered with either CT-P13 (n = 125) or infliximab (n = 125) (in two groups). To check the efficacy and safety profile, concentration-time curve (AUC) at steady-state and observed maximum steady-state serum concentration (C max , ss) was evaluated.…”