Are Patients at Risk for Recurrent Disease Activity After Switching From Remicade® to Remsima®? An Observational Study

Abstract

Background: Since the late '90s, infliximab (Remicade ®) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, infliximab biosimilars, including Remsima ® were introduced in clinical practice. Aim: To investigate the interchangeability of Remicade ® (originator infliximab) and its biosimilar Remsima ® in patients with rare immune-mediated inflammatory diseases (IMIDs). Methods: This two-phased prospective open label observational study was designed to monitor the transition from Remicade ® to Remsima ® in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation. Results: Forty eight patients treated with Remicade ® were switched to Remsima ® in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (n = 17), Behçet's disease (n = 12), non-infectious uveitis (n = 11), and other diagnoses (n = 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (n = 7) or adverse events (n = 5) within 2 years; 10 of these patients discontinued Remsima ® treatment, one withdrew from the study and one received additional corticosteroid therapy. Xue et al. Recurrent Disease Activity on Remsima ® Conclusions: We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade ® to Remsima ®. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade ® to Remsima ®. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires wellconsidered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening.

Switching to an Infliximab Biosimilar Was Safe and Effective in Dutch Sarcoidosis Patients

“…However, the study did report therapy failure or exacerbation of neurological symptoms in a substantial number of patients who were diagnosed with granuloma, including (neuro)sarcoidosis. In contrast to Xue et al, we did not observe a large number of patients to have treatment failure/exacerbation during our 6 months versus their 2 years [ 25 ] follow-up.…”

“…In our study, there was no relapse observed in seven neurosarcoidosis patients during the 6 months follow-up. In addition, Xue et al conducted a prospective observational monitoring study of 48 rare immune-mediated inflammatory diseases patients (among which 17 with sarcoidosis) that were switched from Remicade ® to Remsima ® [ 25 ]. No significant differences were observed for patient-reported outcomes, physician perception disease activity, and laboratory parameters after switching from Remicade ® to Remsima ® .…”

Patients Retransitioning from Biosimilar TNFα Inhibitor to the Corresponding Originator After Initial Transitioning to the Biosimilar: A Systematic Review

“…However, this study included only eight patients, all diagnosed with neurosarcoidosis. Xue et al [ 33 ] also reported failure of infliximab biosimilar in patients with neurosarcoidosis, with effect regained after retransitioning. The authors attributed this finding to variations in afucosylation between the originator and biosimilars, which might be associated with differences in biological activity specifically in sarcoidosis [ 33 ].…”

“…Overall, these studies concluded that there were no major safety issues, including immunogenicity, after transitioning [14]. However, some studies have shown that patients who transitioned to a biosimilar experienced loss of effect and/ or adverse events (AEs), resulting in higher discontinuation rates than in patients who remained on the originator [15][16][17][18]. It has also been shown that, of all patients who transitioned from originator to biosimilar, 2.6-25.8% restarted treatment with the originator (retransitioning) [16,19].…”

Advances in the Treatment of Behcet’s Disease

“…Recently, biosimilars are also used in BD patients. Although a first study has shown a loss of efficacy in 3 patients after switch to an IFX biosimilar, subsequent studies reported good efficacy and safety profile of IFX biosimilar after a start or switch from the originator [11][12][13][14].…”