Introduction
Subcutaneous (SC) infliximab (IFX) is effective in maintaining biochemical, clinical and endoscopic remission rates (1,2,3) in inflammatory bowel disease (IBD) patients. Moreover, it has an excellent safety profile, particularly for immunological issues. Intestinal ultrasound (IUS) is a non-invasive and reliable tool that is currently gaining popularity for IBD monitoring. (4) Transmural healing is considered a desirable long-term treatment endpoint, especially in Crohn’s disease (CD). (5) Whether switching from intravenous (IV) to SC IFX is effective in maintaining transmural remission in IBD is still not known.
Aims & Methods
This is a preliminary report from a prospective multicentre cohort study on both ulcerative colitis (UC) and CD patients treated with IFX. Patients on IV-IFX treatment for at least one year, on clinical, endoscopic and transmural remission were judged to be eligible for switching to SC-IFX. Patients were prospectively followed-up with clinical and biochemical parameters (fecal calprotectin, FC; C-reactive protein, CRP) over a period of 12 months at specific time points (baseline, 3, 6 and 12 months). Therapeutic drug monitoring was evaluated with trough levels and anti-drug antibodies. IUS was performed at baseline and every six months, during which bowel wall thickness (BWT) at terminal ileum (cut-off 3 mm), and at each colonic segment (cut-off 4 mm) was assessed. Limberg score for vascularization, and presence of mesenteric activation, lymphadenopathy and abdominal effusion were assessed. Clinical, biochemical, transmural remission rates and safety profile were prospectively evaluated.
Results
Thirty-six IBD patients were enrolled: males 72%, age 41.7 (± 13.14), 61% with CD. Perianal disease was present in 66% of CD patients. Mean disease duration was 9.1 ± 6.7 years, and patients had been receiving IFX therapy for a mean time of 5.88 ± 3.77 years. All patients showed normal BWT and vascularization (Limberg score <= 1) at baseline.
Median bowel wall thickness was 2.2 (IQR 1.6-2.6) mm for ileum; 2.0 (IQR 1.7-2.5) mm for right colon; 2.2 (IQR 2.0-3.0) mm transverse; left colon 2.7 (IQR 2.0-3.0) mm. Lymphadenopathy was reported in 4 patients (11.1%) and a mild abdominal effusion in 1 patient (2.7%). Mean follow-up time was 212.13 ± SD 122.87 days (range 28-357 days). All patients maintained IUS transmural remission with a median bowel wall thickness of 2.8 (IQR 2.2-3.0) mm for ileum; 2.6 (IQR 2.2-2.8) mm for right colon; 2.5 (IQR 2.0-2.8) mm transverse; left colon 3.6 (IQR 3.2-4.0) mm and a Limberg score <=1; abdominal effusion documented in a patient at baseline resolved by week 24. No statistically significant increase in FC levels (median FC 43 ug/g at T0, IQR 34-108 ug/g; median FC 26 ug/g at T6, IQR 18-48 ug/g; p >0.05), nor in CRP were observed. In only 3 (8.3%) patients a transitory increase in FC (FC > 250 ug/g) was observed, unrelated to IUS or endoscopic activity. No patients discontinued therapy with SC-IFX, treatment was overall well tolerated: six mild infective events, two mild cutaneous injection reaction were observed, with no patient developing severe adverse events (SAEs) during the study period. To date all patients are still in clinical remission, including perianal disease, on treatment with SC-IFX.
Conclusion
Switching from IV to SC infliximab in a selected cohort of IBD patients is safe and effective in maintaining clinical, biochemical and transmural remission. IUS is a useful, non-invasive and low-cost tool for periodic disease assessment.
References
1. Schreiber, Stefan et al. “Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease.” Gastroenterology vol. 160,7 (2021): 2340-2353
2. Smith, Philip J et al. “Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study.” Journal of Crohn's & colitis vol. 16,9 (2022): 1436-1446.
3. Huguet, Jose M et al. “Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study.” Biomedicines vol. 10,9 2130. 30 Aug. 2022.
4. Fraquelli M et al. “Impact of intestinal ultrasound on the management of patients with inflammatory bowel disease: how to apply scientific evidence to clinical practice.” Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver vol. 52,1 (2020): 9-18.
5. Turner, Dan et al. “STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.” Gastroenterology vol. 160,5 (2021): 1570-1583.
