Safety, efficacy and immunogenicity of switching from innovator to biosimilar infliximab in patients with spondyloarthritis: a 6-month real-life observational study

Abstract

Biosimilar infliximab (INX) was recently approved by the European Medicine Agency for the treatment of rheumatoid arthritis, ankylosing spondylitis (AS), Crohn's disease, ulcerative colitis, psoriatic arthritis (PsA), and psoriasis on the grounds that its pharmacokinetics, safety, and efficacy were comparable to those of innovator INX. The aim of this study was to investigate the real-life efficacy, safety, and immunogenicity of switching from innovator to biosimilar INX in patients with spondyloarthritis (SpA). Forty-one patients attending three Italian rheumatology centres with a previous diagnosis of SpA and clinically inactive or moderate disease activity (ASDAS-CRP < 2.1; 22 with AS, five with enteropathic arthritis, 10 with PsA, and four with undifferentiated SpA), who had been treated for more than 6 months with innovator INX in accordance with the ASAS/EULAR guidelines, were switched to biosimilar INX for pharmaco-economic reasons (Tuscany Law No. 450 of 7 April 2015) and followed up for 6 months. A record was kept of their BASDAI, BASFI, ASDAS-CRP, DAS28-CRP (in the presence of peripheral disease), MASES, VAS pain scores, the duration of morning stiffness, and adverse events (AEs). At the time of the switch, the patients had a median age of 50.9 years (range 23-80), a median disease duration of 124.5 months (range 14-372), and a median duration of treatment with innovator INX of 73.7 months (range 6-144). After 6 months of biosimilar INX therapy, there were no statistical differences in their median BASDAI (2.73 ± 1.5 vs. 2.6 ± 1.3, p = .27), BASFI (2.34 ± 1.3 vs. 2.17 ± 1.2, p = 0.051), ASDAS-CRP (1.35 ± 0.3 vs. 1.28 ± 0.2, p = 0.24), DAS28-CRP (2.66 ± 0.67 vs. 2.67 ± 0.35, p = 0.92), MASES (0.35 ± 0.7 vs. 0.17 ± 0.4, p = 0.08), or VAS pain scores (18 ± 14.7 vs. 16.7 ± 11.3, p = 0.55), whereas the median duration of morning stiffness had significantly decreased (7.2 ± 6.9 vs. 5.8 ± 6, p = 0.02). Furthermore, there was no change in circulating INX (4.22 ± 2.89 vs 4.84 ± 2.86 μg/mL, p = 0.80) or anti-INX antibody levels (27.76 ± 17.13 vs 27.27 ± 17.28 ng/mL, p = 0.98). The switch from innovator to biosimilar INX in this Italian multicentre SpA cohort was not associated with any statistically significance differences in efficacy, adverse events or anti-drug antibody level.

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

“…There was a need for additional medication to control increased disease activity after switching from originator to biosimilar infliximab in four of 83 patients with inflammatory bowel disease (IBD) [68] and in 13 of 28 patients undergoing chemotherapy and switching epoetins [77]; a significant increase in median C-reactive protein values (from 1.95 to 4.0 mg/L; P  < 0.05) and median pain scores (from 28.8 to 38.1 mm on a scale of 0–100; P  < 0.05) in patients with IBD switching from originator to biosimilar infliximab [43]; a significant increase in disease activity (mean Bath Ankylosing Spondylitis Activity Index, from 3.8 to 4.3; P  < 0.05) in patients with spondyloarthritis after switching to biosimilar infliximab [71]; a small, significant increase in total daily insulin dose (from 0.62 to 0.65 U/kg/day; P  < 0.05) in patients with type 1 or type 2 diabetes mellitus switched to a biosimilar insulin [87]; but a significant decrease (i.e. improvement) in duration of morning stiffness [median duration, from 7.2 to 5.8 (no units provided); P  = 0.02] in patients with arthritis switching from originator to biosimilar infliximab [47]. In the three remaining studies that included statistical analyses, IBD disease activity significantly improved in paediatric patients switched from originator to biosimilar infliximab ( P  < 0.05; actual values not reported) [66], but significantly worsened in adults who underwent a similar switch (median IBD-Control-8 score, from 11 to 14; P  < 0.05) [63], and primary failure was significantly lower in patients with IBD switched from originator to biosimilar infliximab than in patients switched from other biologics or who were treatment naïve (0 vs 11 and 10%, respectively; P  < 0.05) [50].…”

“…In terms of safety data after switching, eight studies reported no concerns or similar safety profiles before and after switching [43, 44, 47, 50, 62, 63, 79, 87, 89], six studies reported no general safety data [45, 51, 72, 77, 83, 90], and 12 studies reported adverse events such as injection site pain, acute hypersensitivity reactions, rash and infusion reactions after switching (although most did not provide comparative data from before switching) [46, 48, 49, 52, 54, 58, 65–68, 71, 88]. …”

“…5 patients discontinued INXNRAla et al 2016 (abstract) [44]With IBD ( N  = 20)20INX RP, duration NRCT-P13, 6 months post-switchMost patients remained in clinical remission or improved during follow-up (actual numbers NR)No significant AEs reported post-switchNRArguelles-Arias et al 2017 [45]With IBD ( N  = 120)98Originator INX, median duration 297 weeks, or INX-naiveCT-P13, follow-up 6 monthsRemained in clinical remission, switched vs naïve, CD, 3 months: 88 vs 67%; 6 months: 84 vs 50%. UC, 3 months: 92 vs 44%; 6 months: 91 vs 67%NR separately for the 2 treatment groupsNRBennett et al 2016 (abstract) [46]With IBD ( N  = 104)104INX RP, median time 162 weeksCT-P13, follow-up 6 monthsPre-switch vs post-switch, median CRP: 2 vs 2 ( P  = 0.81); median DAS: 1 vs 1 ( P  = 0.44); remission: 85 vs 81% ( P  = 0.51)After switch: 4 patients had AEs (2 minor infusion reactions, 2 skin disease); 19 patients stopped treatment (6 electively, 9 loss of response, 4 for other reasons)Pre-switch vs post-switch: 29 vs 27 patients ( P  = 0.88)Benucci et al 2017 [47]With SpA ( N  = 41)41Originator INX, median duration 74 monthsBiosimilar INX, follow-up 6 months6 months before vs 6 months after switch, median BASDAI (2.6 vs 2.7), BASFI (2.2 vs 2.3), ASDAS-CRP (1.3 vs 1.4); DAS28-CRP (2.7 vs 2.7), MASES (0.2 vs 0.4), VAS pain (17 vs 18) (all P  > 0.05). Median duration of morning stiffness 7.2 vs 5.8 ( P  = 0.02)No significance difference in AEs (Fisher test P  = 1.0; actual data NR).…”

Rapid loss of efficacy of biosimilar infliximab in three patients with Behçet’s disease after switching from infliximab originator

“…Most of these studies seem to be reassuring in terms of efficacy maintenance and safety (9)(10)(11). However, in a recent report, of 23 patients with stable disease remission who were switched from re-IFX to bio-IFX, 7 experienced disease flare-ups after a mean interval of 2 months (12).…”

Biomarkers and Pathogenic Mechanisms in Autoimmunity

“…Patients from three rheumatology centers were switched to biosimilar infliximab and followed during 6 months. Biosimilars were found to be as effective as the innovator ones and with similar efficacy, and with no adverse events or the development of antidrug antibody [15]. Among the many immune-mediated diseases, the following were presented in different sessions.…”