Introduction
Biosimilars are used for the treatment of inflammatory bowel disease (IBD). However, data on the switch from one biosimilar to another still lack. We aimed to study, in an IBD cohort, the effects of the CT-P13-to-SB2-switch, in terms of effectiveness, safety, psychological implications, pharmacokinetic and inflammatory marker levels.
Aims & Methods
Consecutive CT-P13-to-SB2-switched IBD patients were enrolled and prospectively followed-up for 12 months (mo). Patient-reported outcomes (PROs) were employed: specific PRO-2 for CD and UC, IBD-Disability Index (IBD-DI), Functional Assessment of Chronic Illness Therapy Fatigue (FACIT), Short-IBD-Questionnaire (SIBDQ). Psychometric tests were administered to assess the psychological impact of the switch: Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Believes About Medicine (BMQ). C-reactive protein (CRP) levels, concomitant steroid use, and adverse events of interest (AEIs) were recorded. Serum samples were obtained before and after the switch to measure: infliximab (IFX) and anti-IFX trough levels (TLs), and cytokine (TNF-α, IL-6, IL-8, IL-17A, IL22) concentrations.
Results
We enrolled 119 (73 CD, 46 UC). Median age was 40 years (IQR:27-52), median disease duration 9 years (IQR:4-16). Median duration of pre-switch infliximab was 45 mo (IQR:24.5-75.5); 50 (42.0%) patients had previously received infliximab originator-to-CT-P13 switch (median CT-P13 duration: 28 mo, IQR:27-29). In UC, mean stool frequency scores were 0.2±0.5, 0.4±0.8, 0.7±1.5, 0.2±0.5, and mean rectal bleeding scores were 0.1±0.4, 0.1±0.4, 0.4±0.8, 0.0±0.0, at baseline, 2, 6 and 12 mo (p=ns for all). In CD, mean stool frequency scores were 1.9±2.0, 2.1±2.2, 1.8±1.9, 1.5±1.8(p=ns for all), and mean abdominal pain scores were 0.5±0.7, 0.4±0.6, 0.3±0.6, 0.2±0.5 (p=ns for all, expect baseline vs.12 mo p=0.01) at baseline, 2, 6 and 12 mo. Patients in SFCR were 100 (84.0%) at baseline, 97 (81.5%) at 2 mo (p=ns vs baseline), 86 (72.3%) at 6 mo (p=0.03 vs baseline) and 90 (75.6%) at 12 mo (p=ns vs baseline). Mean CRP levels were constantly <5mg/L (3.4±8.0, 3.2±5.8, 2.4±4.0, 2.2±5.7, at baseline, 2, 6 and 12 mo, p=ns for all). No significant changes in psychometric assessments were observed during follow-up in regard to: HADS (10.3±6.8 at baseline, 10.6±8.1 at 2 mo, 11.3±8.1 at 6 mo), PSS (14.3±7.8, 15.7±8.8, 14.9±8.1), IBD-DI (-0.7±4.6, -1.3±5.9, 9.0±4.7), FACIT (42.2±8.9, 40.6±10.8, 41.8±8.6), SIBDQ (55.2±11.4, 54.1±11.8, 56.7±10.7), BMQ-S1-SS1 (18.0±3.4, 18.0±2.3, 17.5±2.9), BMQ-S1-SS2 (15.3±2.6, 15.4±2.0, 15.1±1.9), BMQ-S2-SS1 (9.8±3.2, 9.3±2.6, 9.5±2.7), BMQ-S2-SS2 (8.7±2.9, 8.6±3.0, 9.0±2.7). AEIs were observed in 43(36.1%) patients, most commonly infections (17) and arthralgias (15); 3 cancer diagnoses and 2 infusion reactions were recorded. Pre- and post-switch median IFX TLs remained stable (4.07 vs 4.86 µg/mL, p=ns). Anti-IFX antibodies were detected in 5.1% and 2.5% of patients before and after the switch, respectively; de novo antibody formation was observed in one patient after the switch. The median concentration of TNF-α (9.77 vs 9.16 pg/mL, p=ns), IL-8 (9.04 vs 10.10 pg/mL, p=ns) and IL-22 (5.52 vs 6.43, p=ns) remained stable; conversely, a significant increase was observed in IL-6 (1.20 vs 1.73 pg/mL, p=0.01) and IL-17A (0.72 vs 1.08 pg/mL, p=0.02) median concentrations.
Conclusion
Switching from CT-P13 to SB2 can be considered safe, does not significantly affect treatment effectiveness nor drug pharmacokinetic, and is seemingly not associated with major negative psychological implications.
Disclosure
Daniela Pugliese received speaker fees and/or advisory board from AbbVie, MSD, Takeda and Janssen, Pfizer. Giuseppe Privitera received consultancy fees from Alphasigma and Janssen.
Alessandro Armuzzi: consulting and/or advisory board fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi-Tanabe, Novartis, Pfizer, Roche, Sandoz, Samsung Bioepis, Takeda; and research grants from MSD, Pfizer, Takeda and Biogen. The remaining authors declare no competing interests.
