PTU-073 In Patients with IBD Switching from Originator Infliximab (Remicade) to Biosimilar Infliximab (CT-P13) Is Safe and Effective

Abstract

IntroductionBiosimilar infliximab (CT-P13) has been licensed for the treatment of IBD in Europe for over a year with the potential for significant cost savings. However, uptake in the UK has been slow primarily due to concerns over the lack of safety and efficacy data particularly with regard to switching patients from the originator product. We present the preliminary data from a controlled switch programme in a cohort of adult IBD patients.MethodsA prospective study was undertaken to assess the safety and efficacy of switching patients receiving originator infliximab (Remicade) to its biosimilar (CT-P13). Patient demographic data was collected along with disease severity scores (HBI and SCCAI), biological markers of disease activity, drug and antibody levels and PROM data (IBD-Control questionnaire) prior to the switch and at each subsequent infusion visit. Evaluation of the efficacy of biosimilar infliximab at the time of the last infusion was compared with the originator at switch over. Means, medians, and ranges were calculated. Adverse events were prospectively collected.Results78 IBD patients were included in the cohort (63 CD and 15 UC). The average age for the CD and UC patients was 43 and 42 years respectively. The average length of therapy on Remicade prior to the switch was 46 months for CD and 25 months for UC. 66/78 (85%) patients were receiving the standard dosage of 5 mg/kg 8 weekly with 12/78 (15%) either on a shortened interval or a 10 mg/kg dose. 42/63 (67%) of CD patients were in remission at switch over compared to 43/60 (72%) at the most recent infusion (4–6 months). The number of patients with mild, moderate and severe disease remained stable throughout the study period (Mild 10/63 (16%) v 11/60 (18%): Moderate 10/63 (16%) v 5/60 (8%): Severe 1/63 (2%) v 1/60 (2%)). 9/15 (60%) of UC patients were in remission at switch over compared with 11/13 (85%) at the most recent infusion. There was no difference in the mean CRP before and after the switch in either CD patients (5.4 vs 5.6 p=0.32) or UC patients (3.1 vs 3.0 p=0.73). The mean patient questionnaire score data also remained unchanged before and after the switch (CD 4.4 vs 4.0 p=0.56, UC 4.9 vs 3.1 p=0.61). Five patients (3 CD, 2 UC) discontinued infliximab during the study period (3 switched biological class, 1 infusion reaction, 1 deep remission). There were no adverse safety signals with one infusion reaction (1/283 infusions) and the rate of mild adverse events unchanged from before and after the switch.ConclusionSwitching patients with IBD from originator infliximab to biosimilar infliximab appears both safe and effective. Wider uptake in the UK would result in considerable cost savings to the NHS.Disclosure of InterestNone Declared

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

“…All of the 27 observational, non-medical switching studies reported data on main efficacy parameters after switching compared with baseline/before switching (Table 2) [43–52, 54, 58, 62, 63, 65–68, 71, 72, 77, 79, 83, 87–90, 105]. The originator biologics/biosimilars assessed were infliximab (20 studies [43–52, 54, 58, 62, 63, 65–68, 71, 72]), ESAs (two studies [77, 79]), insulin (two studies [83, 87]) and growth hormone (three studies [88–90]).…”

“…The originator biologics/biosimilars assessed were infliximab (20 studies [43–52, 54, 58, 62, 63, 65–68, 71, 72]), ESAs (two studies [77, 79]), insulin (two studies [83, 87]) and growth hormone (three studies [88–90]).…”

“…Of 16 studies that reported statistical analyses, 13 found no statistically significant differences for main efficacy parameters [43, 46–49, 58, 62, 67, 68, 71, 77, 79, 87], although six of these observed changes for some parameters (in favour of the pre-switch and post-switch treatments in five studies and one study, respectively). 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.…”

“…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]. …”

“…IRR naïve vs switched for SAEs and infusion reactions leading to drug withdrawal: 1.10 ( P NS) and 1.88 ( P NS), respectivelyNRGentileschi et al 2016 (letter to editor) [51]With rheumatic diseases ( N  = 23)23INX RP (Remicade ® ), mean duration: 72 monthsCT-P13 (Inflectra ® ), mean 1.7 months7/23 patients (30%) relapsed after switch (5 switched back to INX RP, of whom 4 improved)NRNRGlintborg et al 2016 (abstract) [105] and 2017 [52]With rheumatoid arthritis, SpA or PsA ( N  = 802)802INX RP, duration 6.8 yearsCT-P13, median follow-up 413 daysDisease activity, 3 months pre- vs post-switch: no clinically relevant differences. unchanged in majority of patientsPost-switch treatment discontinuation: 132 patients (lack of effect, n  = 71, AEs, n  = 37)Baseline vs post-switch (data from 2016 abstract, n  = 96): 15 vs 16% ( P  = 0.7)Jung et al 2015 [54]With IBD ( N  = 110)36INX RP, duration NR (study also included naive patients started straight on CT-P13 treatment, with no switch)CT-P13, duration up to 54 weeksINX RP/CT-P13: efficacy maintained in 31/36 patients, CT-P13 discontinued in 3 patients because of lack of efficacy and in 1 patient who wanted to switch back to INX RP (reason NR)INX RP/CT-P13: AEs, n  = 1 patient (skin rash and arthralgia)NRNikiphorou et al 2015 [58]With established rheumatic diseases ( N  = 39)39INX RP (Remicade ® ), mean duration 4 yearsCT-P13, median follow-up 11 monthsPatient-reported outcomes (including pain, fatigue) similar pre-switch vs post-switch (all P NS)11 patients (28%) discontinued CT-P13: ADAs [sample taken before switch, n  = 3; re-activation of tuberculosis, n  = 1; new-onset neurofibromatosis, n  = 1; subjective reasons (details NR), n  = 6 (5 restarted INX RP)]Not assessed after switchingRahmany et al 2016 (abstract) [62]With IBD ( N  = 78)78INX RP; median treatment duration: CD 46 months, UC 25 monthsCT-P13, 4–6 monthsPre- vs post-switch, remission, CD: 67 vs 72%; UC: 60 vs 85%; mean CRP: 5.4 vs 5.6 ( P NS); UC: 3.1 vs 3.0% ( P NS)1 infusion reaction. Rate of mild AEs similar pre- and post-switch (actual data NR).…”