P440 Loss of response and dose escalation of infliximab and adalimumab in Ulcerative Colitis patients: A Systematic Review and Meta-analysis.
Savelkoul, E.(1);Thomas, P.(1);Derikx, L.(1);Den Broeder, N.(1);Römkens, T.(2);Hoentjen, F.(3);
(1)Radboud University Medical Centre, Department of Gastroenterology and Hepatology, Nijmegen, The Netherlands;(2)Jeroen Bosch Hospital- 's-Hertogenbosch, Department of Gastroenterology and Hepatology, 's-Hertogenbosch, The Netherlands;(3)University of Alberta, Division of Gastroenterology- Department of Medicine, Edmonton, Canada;
Background
Anti-Tumour necrosis factor agents are essential therapeutics in moderate-to-severe Ulcerative Colitis (UC). Annual loss of response (LOR) and dose escalation (DE) risk in UC patients have not been systematically evaluated. This study aimed to assess the annual LOR rate and DE rate for infliximab (IFX) and adalimumab (ADA) in UC.
Methods
A systematic search of PubMed, EMBASE and Cochrane Library was conducted from January 2000 to July 2021. Clinical trials and cohort studies assessing IFX and/or ADA use in adult UC patients were included if these reported LOR rates or DE rates. The primary outcomes included (1) the annual LOR per patient-year of IFX and ADA in UC patients and (2) the annual DE rates per patient-year of IFX and ADA. LOR was only assessed in patients who had primary response to IFX or ADA as defined by the authors. LOR was reported as defined by the authors and then categorized in three definition groups: 1) treatment discontinuation due to LOR, 2) treatment intensification defined as dose escalation and/or treatment switch and/or surgery, because of LOR and 3) increase of clinical, biochemical and/or endoscopic disease activity. Dose escalation was defined as any dose increase or interval shortening as reported by the authors. Summary estimates were calculated using random effects models.
Results
Our search yielded 26,320 potentially relevant articles. We analysed 50 unique studies (IFX (n=35) or ADA (n=23)) assessing LOR (IFX: 24 cohort studies, ADA: 21 cohort studies) or DE (IFX: 21 cohort studies, ADA: 16 cohort studies). Follow-up among all studies ranged from 38 to 350 weeks. The pooled annual LOR for IFX was 11.2% (95% CI [0.082-0.153], Figure 1). LOR per category was as follows: 8.3% (95% CI [5.3-13.3]) for discontinuation (n=16), 18.6% (95% CI [11.5-29.8]) for treatment intensification (n=6), 19.3% (95% CI [14.3-26.0]) for increase in clinical/biochemical/endoscopic activity (n=2). The pooled annual LOR for ADA was 15.1% (95% CI [0.103-0.220], Figure 2). LOR per category was as follows: 12.0% (95% CI [7.1-19.9]) for discontinuation (n=16), 43.6% (95% CI [21.8-87.2]) for treatment intensification (n=3), 11.6% (95% CI [4.0-33.9]) for increase in clinical/biochemical/endoscopic activity (n=2). Annual pooled DE rates were 14.7% (95% CI [10.4-20.7]) for IFX and 21.3% (95% CI [15.6-29.0]) for ADA.
Figure 1 - Infliximab
Figure 2 - Adalimumab
Conclusion
The overall pooled annual LOR in UC patients was 11% for IFX and 15% for ADA. LOR rates varied among different used definitions. Annual dose escalation rates were 15% for IFX and 21% for ADA. Future studies in this field should focus on a universal definition of LOR and report time to loss of response.