Systematic switch from innovator infliximab to biosimilar infliximab in inflammatory chronic diseases in daily clinical practice: The experience of Cochin University Hospital, Paris, France
Introduction
Targeted biological treatments have revolutionized and transformed treatment paradigms for chronic inflammatory disorders in rheumatology, as well as in dermatology, gastroenterology, and ophthalmology. However, their significant costs have been a barrier to their use [1], [2].
Recent expiry of patents for some key biologics has led to development of biosimilars. With increasing numbers of biosimilar products, more options are available for patients to access earlier to biological products and possibly switch from costly innovators to biosimilars. Since the approval of the chimeric monoclonal antibody to tumor necrosis factor-ɑ (TNF-ɑ) Infliximab (Remicade®), the biosimilar CT-P13, has entered the market [3]. This is the first biosimilar monoclonal antibody, with the trade names Inflectra® or Remsima®, registered by the European Medicines Agency (EMA) in 2013 [4]. Since then, new biosimilars of TNF-α inhibitors have been developed: Benepali® (biosimilar etanercept), Amjetiva® (biosimilar adalimumab) and Flixabi® (another biosimilar infliximab).
Biosimilarity between CT-P13 and its innovator has been demonstrated by physicochemical, non-clinical, and clinical studies including two pivotal clinical studies [5], [6], CT-P13 development program included a therapeutic equivalence PLANETRA study in 606 patients with rheumatoid arthritis (RA), on background of methotrexate, which showed equivalent efficacy and comparable safety profile, pharmacokinetics and immunogenicity of CT-P13 with innovator infliximab. Similarly, the PLANETAS trial that included 250 patients with spondyloarthritis demonstrated equivalent pharmacokinetic parameters and comparable safety profile, efficacy and immunogenicity of CT-P13 with innovator infliximab.
Thus, based on these comparable results in randomized controlled trials and favorable costs, the medical community of Cochin Hospital decided in October 2015 to systematically propose the switch from innovator to biosimilar infliximab to all treated patients.
It is important to mention that CT-P13 development program only included patients who were naive of infliximab before receiving the first infusion of CT-P13. Moreover, CT-P13 has been approved for use in indications held by the innovator biologic not directly studied in a comparative clinical trial with the biosimilar, like Crohn's disease (CD) and ulcerative colitis (UC). This extrapolation reduces or eliminates the need for duplicative clinical studies of the biosimilar by extrapolating all the data collected from one indication for the biosimilar product to all the indications originally approved for the innovator.
Thus, given the paucity of data related to the consequences of switching to biosimilar infliximab in daily clinical practice, particularly in the subsets of patients suffering from different diseases than those evaluated during the CT-P13 development program and those receiving long lasting innovator infliximab infusions, we decided to collect clinical outcomes in an observational prospective cohort study in a clinical practice setting.
The objective of this study was to investigate on a large array of inflammatory disorders the efficacy in clinical practice (i.e., effectiveness) and safety of systematic switching treatment from innovator infliximab to biosimilar infliximab. In addition, we analyzed the outcome of patients re-established back on innovator infliximab in case of biosimilar discontinuation
Section snippets
Study design
Prospective observational usual care study conducted in Rheumatology, Gastroenterology, and Internal Medicine departments of Cochin Hospital. The Dermatology department was not involved, since no patient with psoriasis was receiving infliximab.
Study population
All patients on maintenance therapy with innovator infliximab and followed-up in Cochin Hospital were systematically screened for inclusion.
Inclusion criteria
Adults who agreed to switch to biosimilar infliximab, and who had received at least 3 infusions of innovator
Statistical analysis
All data are expressed as mean values ± standard deviation (SD) or number and percentage (%) for continuous and categorical variables, accordingly. Statistical analysis was performed using SAS. Comparisons before-after switch were estimated by paired t-test or McNemar test for continuous and categorical variables, accordingly. Retention rate of biosimilar infliximab was estimated by Kaplan-Meier survival curves. Factors associated with discontinuation were estimated by Cox proportional hazards
Study population
A total of 265 patients were on maintenance therapy with innovator infliximab. Five patients were not eligible for inclusion (Fig. 1). No patient declined to participate in this study. In total, 260 patients fulfilled the inclusion criteria, including 182 patients followed-up in Rheumatology, including 131 with axSpA, 31 with RA, and 20 with other inflammatory rheumatic diseases (14 psoriatic arthritis, 3 juvenile arthritis, and 3 undifferentiated inflammatory arthritis). Sixty-four patients
Retention rate of biosimilar infliximab at the last study visit
At the last study visit, patients had received a mean of 4.6 ± 1.1 infusions of biosimilar infliximab, with a mean dose of 413 ± 157 mg and a usual inter-dose interval of 8.2 ± 1.8 weeks (Table S1). At this visit, a total of 201 patients (77%) were still on this treatment (Fig. 1). The retention rate was significantly lower in rheumatology (134/182, 74%) compared to the rate observed in Gastroenterology and Internal Medicine (67/78, 86%, P = 0.034). Patients with AxSpA had the lowest retention
Discussion
We report one of the first experiences of a systematic switch from innovator infliximab to its biosimilar in patients with various inflammatory conditions in a single tertiary center. Our study brings additional relevant data to the previous published RCTs, since we focused on a population that was long-term treated with innovator infliximab, we considered diseases that were not included in these trials, such as IBD and uveitis, and we studied the outcome of patients re-established back on
Acknowledgments
Gerturde TOUANGA NGOTI and Clotilde SIMON, Unité de Recherche Clinique Cochin/Necker.
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Recurrence Rates of Inflammation after Switching from the Originator Infliximab to Biosimilar Infliximab-abda for Noninfectious Uveitis
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These authors equally contributed to this work.