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- DMARDs (biologic)
- rheumatoid arthritis
- patient attitude to health
- nocebo effect
To date, all available data regarding the switch from bio-originator to its biosimilar are reassuring, and the switch has been recommended as a shared patient–physician decision in recent consensus-based recommendations.1 In particular, the Norway's infliximab switching study (NOR-SWITCH study), a 52-week randomised double-blind trial, strongly supports the efficacy and safety of the switch from originator infliximab (OI) to its biosimilar CT-P13 in patients with a stable disease.2 However, long-term follow-up data are required to confirm the efficacy and safety of the switch.
In a previous real-life study, we demonstrated a high acceptance of 89% (89/100) and a 72% (64/89) retention rate after a median follow-up of 33 weeks in a cohort of patients with stable rheumatic diseases switched from OI to CT-P13.3 This retention rate was lower compared with two control cohorts: a historic cohort of 82 patients treated with OI in 2013, and a prospective cohort of 29 infliximab-naïve patients beginning CT-P13. Interestingly, 44% (11/25) of switched patients who had CT-P13 withdrawn did not present any objective disease activity defined as bath ankylosing spondylitis disease (BASDAI) ≥4 and physician global assessment ≥4 for spondyloarthritis/28-joint disease activity score-C-reactive protein (DAS28-CRP) ≥3.2 with ≥1 swollen joint for rheumatoid arthritis, suggesting a nocebo effect or incorrect causal attribution bias. When considering only patients with objective activity as CT-P13 failure, differences between cohorts faded, suggesting the neutrality of the switch in terms of efficacy and safety.
In the present work, our goal was to assess the long-term retention rate of CT-P13 after switching from OI, and to compare it with the retention rate observed in the historic cohort of patients treated with OI described in our previous study.3
In the switch cohort, 50/89 (56%) patients were still treated with CT-P13 after a median follow-up of 120 weeks (range 6–145). Among the 39 withdrawals, 25 (64%) patients discontinued CT-P13 during the first period of follow-up,3 whereas 14 (36%) patients discontinued CT-P13 later. Reasons for stopping CT-P13 belatedly were: an objective clinical worsening in 5/14 patients, non-serious safety issues in 6/14 patients (psoriatic lesions, digestive disorders, asthenia and subjective neurological symptoms with negative extensive investigations as detailed in online supplementary data and stable remission in 3/14 patients. No case of subjective clinical worsening was observed during the second period of the follow-up.
Treatment retention rates were 67% (55/82) for OI in the historic cohort after a median follow-up of 131 weeks (range 4–156). Survival curves of treatment retention taking all causes of withdrawals into account are shown in figure 1A. There was a statistical trend towards more withdrawals in the switch population compared with the historic cohort, as assessed by the log-rank analysis (p=0.052). After excluding patients without worsening objective clinical activity, this statistical trend faded (log-rank p=0.673;, see figure 1B). Interestingly, infliximab retention rates were similar between the switch and the historic cohort when starting the analysis from the end of the first study as represented in figure 1C (log-rank p=0.708).
These results suggest that a nocebo effect may occur in the first weeks after the switch and initially lowers the biosimilar retention rate, as already demonstrated in previous studies.3–5 Thereafter, OI and CT-P13 retention rates appear to be identical, confirming the safety, efficacy and acceptability of the switch in the long term. One strength of our study is a long-term follow-up after the switch. Initial information provided before the switch appears to be crucial for biosimilar acceptance and therefore reducing the nocebo effect.6 Patient and physician information on long-term efficacy and safety of biosimilars are consequently a major need to enhance their widespread use.
Handling editor Josef S Smolen
VG and MS contributed equally.
Contributors VG and MS collected the data and wrote the manuscript. MS and TB analysed the data. TS designed the study and helped in data analysis. All authors critically reviewed the paper and validated the last version of it.
Competing interests TS received honoraria as consultant from: Amgen, AbbVie, BMS, Janssen, MSD, Novartis, Pfizer, Roche Chugaï, UCB. TS received a research grant from Pfizer (unrelated to this work). The other authors report no conflicts of interests.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.