P799 Infliximab and immunomodulator combination therapy in inflammatory bowel disease – no longer inseparable?
Carlson, S.(1)*;Evgeniou, V.(1);Kok, K.(1);
(1)Royal London Hospital- Barts Health NHS Trust, Gastroenterology, London, United Kingdom;
Background
The gold-standard for prescribing Infliximab (IFX) in IBD is to use it in combination with an immunomodulator (IMM), thereby reducing the risk of immunogenicity and improving overall outcomes. This practice, however, comes with considerable increased risk of adverse events. There is mounting evidence that withdrawal of IMMs, especially after 6 months of combination therapy (CT), does not reduce IFX trough levels or increase the risk of loss of response (Drobne et al., 2015; Mahmoud et al., 2022). We identified IBD patients on IFX CT who were eligible to stop their IMM based on defined criteria and assessed clinical outcomes of patients who had previously had their IMM withdrawn.
Methods
This was a retrospective cross-sectional study in a central London tertiary hospital. We included patients with a diagnosis of Crohn’s Disease (CD), Ulcerative Colitis, or Indeterminate colitis, with therapeutic IFX levels >5mg/ml, undetectable anti-drug antibodies (ADA) (<10 AU/ml) and at least 6 months of CT from induction between January 2017 and December 2021. Patients were identified on an immunology laboratory database and electronic patient records were manually assessed for baseline characteristics and clinical outcomes. The primary timepoint of interest for clinical outcomes is 4 months after measurement of IFX drug levels.
Results
A total of 825 IBD patients had IFX drug levels performed in the defined time-period. 296 patients had IFX levels >5mg/ml and undetectable ADAs; of these 160 (54%) had been on CT for >6 months. Baseline characteristics were 41.3% (n=66) female, mean age (y) of 29 (SD ±14) and 70.6% (n=113) had CD. In the 4 months after IFX drug assays, 140 of 160 (87.5%) patients remained on CT whereas 20 (12.5%) had previously stopped their IMM. Of those on CT, 90.7% (127/140) were in clinical remission at the time of the assay compared to 90% (18/20) of patients in the IMM withdrawal group (p=0.46). At the time of data collection, 79.3% (111/140) of CT patients remained on IFX therapy compared to 75% (15/20) who withdrew IMMs (p=0.33, median follow up 19 months). IMM withdrawal was predominantly due to side effects (n=16, 80%) with the remainder due to clinical remission (n=4, 20%). The 2/20 (10%) patients with active disease in the IMM withdrawal group were active prior to stopping IMMs.
Conclusion
Patients with good IFX drug levels and undetectable ADAs after at least 6 months of IFX CT did well regardless of whether they withdrew IMMs or not, supporting recent studies that suggest it is safe to do so. Given the number of our patients who could potentially benefit from stopping their IMMs, prospective controlled studies are required to determine whether this is advisable given the theoretical risk of loss of response.