THU0354 Disease worsening and safety in patients switching from originator infliximab to biosimilar infliximab (CT-P13) in the randomized nor-switch-study: explorative analysis in SPA patients

Abstract

BackgroundThe NOR-SWITCH study is a 52-week randomized, double-blind, non-inferiority, phase IV switch trial in patients with Crohn's disease (CD), ulcerative colitis (UC), spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and plaque psoriasis (Ps) on stable treatment with originator infliximab (Remicade®, INX), funded by the Norwegian government. Previously, primary analyses of the pooled indications have been published1.ObjectivesTo investigate efficacy, safety and immunogenicity in SpA patients treated with continuous INX vs patients switched to CT-P13 (biosimilar infliximab, Remsima®) in the NOR-SWITCH study (explorative analyses).MethodsPatients were randomized 1:1 to continued INX or switch to CT-P13. Serum drug levels were analyzed by automated in-house assay. The primary endpoint was disease worsening according to disease-specific composite measures and/or consensus between investigator/patient. Exploratory subgroup analyses examined disease worsening and safety in SpA. The primary endpoint was analysed by logistic regression, adjusted for diagnosis and disease duration.ResultsDemographics, occurrence of disease worsening, change in disease measures and treatment-emergent adverse events (TEAE) were similar (Table), as were serum drug levels for INX and CT-P13 (Figure).Table 1.Demographics, baseline characteristics (FAS), percentage of patients with disease worsening, change in disease measures during 52 weeks follow-up (PPS)Demographics, baseline characteristicsINXCT-P13 Total number of SpA patients PPS/FAS43/4542/46Age (years) mean (SD)50.0 (10.3)52.8 (10.8)Females7 (16%)8 (17%)Duration of ongoing INX treatment (years) mean (SD)8.6 (3.1)8.7 (3.2)Immunosuppressive co-medication15 (33%)10 (22%)HLA B27 pos31 (94%)33 (87%)Disease worsening95% CI of group difference after 52 weeks All study patients53 (26.2%)61 (29.6%)-12.7–3.9% SpA17 (39.5%)14 (33.3%)-14.5–27.2%Change in disease measures from baseline Physician Global Assessment of Disease Activity (0–10)-0.1 (1.4)-0.5 (1.3)0.53–0.53 Patient Global Assessment of Disease Activity (0–10)0.1 (2.2)-0.4 (1.8)-0.08–0.62 Log10 erythrocyte sedimentation rate (mm/h)0.0 (0.3)-0.0 (0.3)-0.14–0.06 Log10 C-reactive protein (mg/L)-0.0 (0.4)-0.1 (0.4)-0.11–0.15 ASDAS0.1 (0.6)-0.2 (0.7)-0.27–0.24 BASDAI0.3 (1.0)-0.2 (1.4)-0.50–0.47TEAE (FAS)116102Data are n (%), mean (SD) or median (25–75 percentiles). 95% CI, 95% confidence interval of the adjusted treatment difference. BASDAI, Bath Ankylosing Spondylitis Disease Activity Index. ASDAS, Ankylosing Spondylitis Disease Activity Score. FAS, Full Analysis Set. PPS, Per Protocol Set. TEAE, treatment emergent adverse events.ConclusionsExplorative analyses in the NOR-SWITCH study showed similar efficacy, drug levels and safety in SpA patients switched to CT-P13 as those on continuous INX. The study was not powered to show non-inferiority within each diagnosis.References Jørgensen KK et al. Switching from originator infliximab to biosimilar CT-P13 compared to maintained treatment with originator inflixim...

Systematic review: efficacy and safety of switching patients between reference and biosimilar infliximab

“…Among the other patient subgroups, disease worsening, immunogenicity, and safety profiles were similar across the reference infliximab and CT‐P13 groups . However, these sub‐studies were not powered to evaluate non‐inferiority …”

“…Further exploratory analyses of safety, efficacy, and immunogenicity, in spondyloarthritis, RA, CD, and UC patient subgroups in NOR‐SWITCH were also conducted . In the largest of these cohorts (CD; N = 129), disease worsening occurred in more frequently in the switch arm (36.5%) than the maintenance arm (21.2%; 95% CI of adjusted difference, −29.3% to 0.7%) .…”

“…In the largest of these cohorts (CD; N = 129), disease worsening occurred in more frequently in the switch arm (36.5%) than the maintenance arm (21.2%; 95% CI of adjusted difference, −29.3% to 0.7%) . Among the other patient subgroups, disease worsening, immunogenicity, and safety profiles were similar across the reference infliximab and CT‐P13 groups . However, these sub‐studies were not powered to evaluate non‐inferiority …”

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: 12 months results

“…In the current study, AEs occurred in 11 of the 98 (11.2%) patients with IBD. To date, no unexpected treatment-emergent adverse events (TEAEs) have been observed in patients with CD and UC treated with CT-P13 17 – 25 . A Korean study in 95 patients with CD and 78 patients with UC treated with CT-P13 reported that treatment-related TEAEs occurred in 10% of patients.…”

“…In patients with IBD, a number of observational studies of CT-P13 in clinical practice in both anti-TNF-α-naive patients 17 – 22 and those who have been switched from infliximab RP 23 , 24 have been published with good results. Furthermore, results from the randomized, phase IV, double-blind, parallel-group NOR-SWITCH study (NCT02148640) have recently been reported 25 and other similar randomized controlled trials have been initiated in patients with IBD 26 , 27 but are either ongoing or awaiting results. On the basis of the current regulatory guidance from the EMA, and the evidence for efficacy and safety of biosimilars in patients with IBD, the European Crohn’s Colitis Organisation has recently published its position statement on the use of biosimilars for IBD 28 and states that ‘when a biosimilar product is registered in the European Union, it is considered to be as efficacious as the reference product when used in accordance with the information provided in the Summary of Product Characteristics’.…”