Abstract and Introduction
Abstract
Objectives: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process.
Methods: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7–10 on a 10-point rating scale (where 10=agree completely).
Results: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0–1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target.
Conclusions: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.
Introduction
Inflammatory bowel diseases (IBD) are chronic, progressive, and disabling conditions. Most current strategies, which target control of symptoms, do not appear to significantly alter the natural course of the disease, although reductions in the need for surgery or the occurrence of neoplasia have been reported in some ulcerative colitis (UC) and Crohn's disease (CD) population-based cohorts over time. Recent studies underscore the need to look beyond symptoms and to treat endoscopic/macroscopic lesions in both CD and UC with the final aim of preventing structural damage and disability. Whether histologic healing should be an ultimate therapeutic goal is debated.
It is not feasible to repeat frequent endoscopies or cross-sectional imaging for reasons of cost and/or the invasive nature of these procedures; therefore, surrogate biomarkers of inflammation, including C-reactive protein (CRP) and fecal calprotectin have been increasingly studied in IBD, although their ability to replace endoscopic, histologic, and cross-sectional imaging studies remains ambiguous.
Acknowledging the need to accurately measure both the patient's experience with the disease and biological manifestations of disease, the US Food and Drug Administration (FDA) is moving from the Crohn's Disease Activity Index (CDAI) as a clinical trial end point toward patient-reported outcomes (PROs) and objective measures of disease, such as findings from endoscopy. The European Medicines Agency has not adopted such recommendations as of yet.
A "treat-to-target" strategy has been advocated as an optimized management approach for rheumatoid arthritis (RA). This approach is focused on achieving remission or low disease activity, based on insights from various clinical trials as identified through a systematic literature review. The purpose of strict definitions of treatment targets is to facilitate strategic actions in routine clinical practice. Accordingly, physicians and patients should discuss such targets and work toward achieving them by adopting therapeutic changes within distinct time frames, ideally following therapeutic algorithms. This approach has been used in many areas of medicine, where treatment targets have been defined to improve outcomes and reduce the risk of end-organ damage (such as joint damage in RA and macrovascular or microvascular complications of diabetes mellitus).
The objective of the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative, under the auspices of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), was to achieve international expert consensus on appropriate evidence-based treatment targets for IBD that could be used in treat-to-target strategies in routine clinical practice.