A total of 222 patients receiving Remicade® treatment were informed about the option to switch to the biosimilar, of which 192 agreed to transition and to collection of their outcome data as part of this study (BIO-SWITCH). Among these, the indications for treatment were rheumatoid arthritis (RA; n=75), psoriatic arthritis (PsA; n=50) and ankylosing spondylitis (AS; n=67). All had longstanding disease (median duration 14 years) and had been treated with Remicade® for a median of 7 years.
Overall, the mean DAS28-CRP in RA and PsA patients remained stable over the 6-month study. However in AS patients, the mean BASDAI increased (difference of +0.5 [9% CI 0.1 - 0.9]). The CRP levels, infliximab trough levels, and anti-infliximab antibody levels did not change.
During the six months of the study, the biosimilar was stopped in 47 patients (24%) due to a perceived lack of effect (n=26), an adverse effect (n=11) or a combination (n=10) [the authors comment that the majority of the adverse effects could be categorized as subjective health complaints]. Among these, Remicade was restarted in 37, 7 switched to another biological and 3 continued without biologic drugs.
When the authors analysed the results from the subgroup who discontinued the biosimilar, they found that the DAS28-CRP (RA and PsA) immediately prior to discontinuation was increased relative to baseline (by +0.8 (95% CI 0.3 to 1.3) points, and that this was caused by increases in subjective (e.g. patient's global assessment of disease activity), but not objective (e.g. swollen joint count), assessments.
The authors comment that the rate of discontinuation of the biosimilar due to subjective health complaints seen in this study (and in other open-label transition studies) is much higher than that seen in the blinded NOR-SWITCH trial. In their view this can be explained by the awareness by both patients and physicians of the transition to a biosimilar, with two recent surveys highlighting concerns about effectiveness and safety. They therefore suggest that the increase in subjective assessments may be explained by nocebo effects (where patients’ own negative expectations may induce negative symptoms) and/or incorrect causal attribution effects (where increases in disease activity or adverse events that occur independently of the transition may be falsely attributed to the transition). They therefore suggest that communication is an important determining factor in the success of transitioning to a biosimilar drug in daily practice.
NHS England are undertaking a programme of work to improve clinician confidence and clarify understanding amongst decision makers, such as commissioners, clinicians, pharmacists and patients in their consideration of the appropriate use of biosimilar medicines.
A NICE key therapeutic topic (last updated January 2017) summarises the evidence-base on biosimilar medicines.