What are the treatment targets in inflammatory bowel disease (IBD) in 2020?: Session one summary

Abstract

Improved outcomes in inflammatory bowel disease (IBD) in 2020 are due to both an increased number of effective medical therapies, and improved strategies for using these agents. These strategic advances, driven by results from well-designed prospective studies and internationally accepted guidelines, have culminated in the gradual adoption of a treat-to-target strategy as the standard of care in IBD management today. Session one of the Choosing Wisely IBD 2020 virtual symposium explored the potential treatment targets in IBD clinical practice today, first via pre-recorded video presentations from local speakers and then with a live state-of-the-art lecture and panel discussion. Dr Britt Christensen (Royal Melbourne Hospital, Melbourne, Australia) discussed the rationale for endoscopic rather than symptom-based treatment targets, before outlining data to support histological treatment targets, an area of recent interest in ulcerative colitis research in particular. Dr Antony Friedman (The Alfred Hospital, Melbourne, Australia) discussed the role of radiological treatment targets, with a focus on intestinal ultrasound, which is increasingly used in Australian IBD clinics. Dr Emily Wright (St. Vincent’s Hospital, Melbourne, Australia) then summarized the role of non-invasive biomarkers as treatment targets, including fecal calprotectin and the future potential of the recently-described serum endoscopic healing index. Dr Nick Kennedy, one of the invited international speakers, then gave a state-of-the-art lecture on integrating a treat to target approach into clinical practice in 2020. The evolution of treatment targets from symptom control to objective targets with progressively deeper levels of biomarker normalization was presented, culminating in the CALM study and STRIDE guidelines. The PANTS study, from the speaker’s institution, was then presented in detail. This was a prospective, multicentre, uncontrolled study of biologic naïve Crohn’s disease patients treated with infliximab and adalimumab, and included 1,610 patients from 120 centers in the United Kingdom. The PANTS study demonstrated the clinical and pharmacokinetic superiority of combination therapy for both infliximab and adalimumab, and showed that achieving clinical, biochemical and pharmacokinetic targets at the end of induction was associated with superior outcomes at one year. In particular, proactive therapeutic drug monitoring during induction to achieve infliximab levels >7 μg/mL or adalimumab levels >12 μg/mL was associated with improved clinical remission rates at one year, while low drug levels at week 14 were associated with the development of immunogenicity and poorer clinical outcomes at 12 months and beyond. Of great potential significance, the study identified the human leukocyte antigen (HLA) DQA1*05 haplotype (present in up to 40% of the European population) as being strongly associated with the development of immunogenicity to anti-TNFs, especially when an anti-TNF is used as monotherapy. Cost-effectiveness data from analyses from several different treat-to-target studies, including CALM, were presented, demonstrating the potential for cost-effectiveness by reducing direct and indirect costs associated with active disease and the need for hospitalization and surgery. It was acknowledged that to deliver high-quality treat-to-target IBD care a multidisciplinary approach is required. As was shown in the PANTS study, the improved outcomes associated with individualization of anti-tumor necrosis factor (TNF) dosing were presented, including the use of proactive therapeutic drug monitoring of adalimumab in the pediatric PAILOT study. A view to the future of treat-to-target medicine in IBD was presented, including the study designs of currently recruiting studies (REACT2 (NCT01698307), STARDUST (NCT03107793), VERDICT (NCT04259138)). New technologies that are starting to reach the clinic were presented, including the use of rapid testing for both anti-TNF drug levels and fecal calprotectin, and the potential for the incorporation of data from artificial intelligence analyses into treatment algorithms. A panel discussion between the invited speakers, live audience, and steering committee on the nuances of the treat-to-target strategy then followed. The concept of individualization of treatment targets by disease phenotype was discussed. For example, in Crohn’s disease, target calprotectin levels will be lower in patients with small bowel disease compared to those with colonic disease, and target anti-TNF drug levels will be higher for patients with perianal disease compared to those with luminal disease. Proactive therapeutic drug monitoring of anti-TNFs was discussed, with speakers and panelists verifying the benefits of attaining high target drug levels at the end of the treatment induction phase. Although other aspects of proactive therapeutic drug monitoring require further validation, it would appear that aiming to optimize anti-TNF dosing during the induction phase is ready for incorporation into clinical practice today. Data on therapeutic drug monitoring for vedolizumab and ustekinumab are less clear, although signals of week six vedolizumab levels >20 μg/mL and improved outcomes during maintenance are emerging. As this stage, therapeutic drug monitoring of non-anti-TNF biologics is not ready for routine ‘prime time’ use. The international speakers discussed the potential for inter-assay variability for all classes of biologics and the need to know the specifications of your assay in interpreting results. Future trends in the individualization of biologic dosing were discussed, with the hope that exciting results from recent studies, such as the HLA DQA1*05 data from PANTS, can be doi:10.1111/jgh.15445