Switch to Subcutaneous Infliximab Maintains Clinical Remission in Patients with IBD

Credit: Sora Shimazaki/Unsplash

A switch from intravenous to subcutaneous infliximab was associated with safely maintained clinical remission in patients with inflammatory bowel disease (IBD), according to new findings from the ENEIDA registry.¹

On October 23, 2023, infliximab-dyyb (ZYMFENTRA) was approved by the US Food and Drug Administration (FDA) for use in adult patients with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) following treatment with infliximab administered intravenously.²

Results from this analysis help confirm the benefit of subcutaneous infliximab among patients with IBD in Spain, as the switch from intravenous infliximab offered higher drug levels and good patient acceptance.¹

“The switch from intravenous to subcutaneous infliximab maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance,” wrote the investigative team, led by Alejandro Garrido-Marín, Hospital Universitari i Politècnic La Fe.¹

The multicenter, descriptive, and observational study included patients with Crohn’s disease and ulcerative colitis (UC) going to be changed from intravitreal infliximab to subcutaneous infliximab in the ENEIDA registry. The ENEIDA registry is a large, prospectively maintained database of the Spanish Working Group in IBD-GETECCU. All included participants were in clinical and biological remission for ≥24 weeks before changing.

From the registry, Garrido and the investigative team collected demographic and disease data, clinical activity (Harvey-Bradshaw index for CD; Mayo Index for UC), analytical data (C-reactive protein and fecal calprotectin), as well as trough levels, at baseline, and at 12 and 24 weeks. The goals of the study were to evaluate the efficacy, safety, pharmacokinetics, and patient experience after a switch to subcutaneous infliximab in patients in clinical remission on intravitreal infliximab maintenance therapy.

Overall, the analysis included 155 patients, including 54 patients (35%) with UC and 91 patients (65%) with Crohn’s Disease. Participants were an average of 45.5 years old and 44% were women. Intravitreal infliximab was primarily administered due to active disease (72%) and perianal disease (7%) over 32 months (range, 14 - 56 months).

Prior to the switch, 78 (50.3%) patients were on 8-weekly dosing of intravitreal infliximab, 77 (49.7%) were with intensification dose, and approximately half (50.3%) were on concomitant immunomodulatory therapy. Most patients switched to subcutaneous infliximab due to the COVID-19 pandemic (60%), to increase through levels (15%), or patient requests (25%).

In addition, most patients (n = 140 [90%]) remained with the standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 patients; 240 mg every 2 weeks in 4 patients), and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 patients; 120 mg every 4 weeks in 3 patients). Garrido and colleagues noted clinical indices, C-reactive protein, and fecal calprotectin.

Analyses showed the median subcutaneous infliximab levels significantly increased from baseline of 4.5 µg/dL (range, 2.6 - 9.2) to 14 µg/dL (range, 9.5 - 16.2) at week 12 and 13.2 µg/dL (range, 10.4 - 19.7) at week 24. No factors, including immunosuppressors, body mass index, or disease location, were found to be associated with an increase in infliximab trough levels.

Over the 24-week follow-up period, 16 of 78 patients (20.5%) stopped immunosuppressant treatment. Adverse events were identified in 9 (5.8%) patients, while 4 (2.6%) were hospitalized and 4 (2.6%) patients had surgery, including 1 for perianal disease. A total of 9 (5.8%) patients stopped subcutaneous infliximab, including 1 for primary failure, 2 for loss of response, 4 for adverse events, 1 for voluntary, and 1 for surgery.

“The significance of high drug levels with subcutaneous infliximab requires further exploration,” investigators wrote.¹

References

1. _{A. Garrido, M.I. Iborra Colomino, B. Caballol Oliva, J.M. Huguet Malavés4, L. Arias García5, F. Mesonero Gismero, et. al. Real-Life Experience of the Efficacy, Safety, and Pharmacokinetic Data of Switching from Intravenous to Subcutaneous Infliximab in Inactive Inflammatory Bowel Disease Patients: Results from the Eneida Registry. Data presented at United European Gastroenterology Week 2023. Copenhagen, Denmark. October 14 – 17, 2023.}
2. _{Campbell P. FDA approves first subcutaneous infliximab for maintenance therapy in UC and Crohn’s disease. HCP Live. October 23, 2023. Accessed October 24, 2023. https://www.hcplive.com/view/fda-approves-first-subcutaneous-infliximab-for-maintenance-therapy-in-uc-and-crohn-disease.}