Use of biologics for the management of Crohn’s disease: IG-IBD clinical guidelines based on the GRADE methodology
FABIO MACALUSO ED Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)
Abstract
A cure for Crohn’s disease (CD), a chronic inflammatory disease of the gastrointestinal tract of unknown etiology, is not available, so patients require lifelong management to keep inflammation under control. The therapeutic armamentarium has expanded with approval of several biological drugs, including infliximab, adalimumab, vedolizumab and ustekinumab – monoclonal antibodies that target different inflammatory pathways – and darvadstrocel, a suspension of expanded human allogeneic, adipose-derived, mesenchymal stromal cells for the treatment of refractory complex perianal fistula. Notwithstanding existing practice guidelines on medical therapy for CD, the Italian Group for the Study of Inflammatory Bowel Disease felt the need to issue new guidelines focused on the use of biologics for managing the intestinal manifestations of CD and based on the GRADE methodology. This document presents recommendations regarding six clinical settings, from the induction to the maintenance of clinical remission, and from optimization and de-escalation of treatments to dealing with perianal CD and post-operative recurrence. The 19 evidence-based statements are supported by information on the quality of the evidence, agreement rate among panel members, and panel comments mainly based on evidence from real world studies.
Keywords
1. Introduction
Crohn’s disease (CD) is a progressive, inflammatory condition of the gastrointestinal tract [1]. It often requires continuous medical treatment, as the etiology of the disease is unknown and, therefore, a curative therapy is not available [1]. Furthermore, the degree of patients’ symptoms does not always match the inflammatory activity, and subclinical or overt inflammation is able to cause the well-known complications of the disease (i.e., strictures, fistulas, abscesses). Over the years, these complications can lead to progressive bowel damage and the need for repeated surgery, with the consequent risks of short bowel and a permanent stoma [2,3]. Thus, there are important unmet needs in the management of CD.
CD management has benefitted by the increased knowledge over the past 20 years of the immunological mechanisms involved in the pathogenesis of the disease. This knowledge has led to the introduction of several biological therapies, monoclonal antibodies that selectively block key mediators of inflammation. For several years, the most advanced therapies for patients with moderate-to-severe CD involved blocking the activity of tumor necrosis factor (TNF) [4]. Infliximab was the first anti-TNF monoclonal antibody approved by the European Medicines Agency (EMA) for the treatment of CD, in 1999, and it was followed by adalimumab in 2007. Later, other biologics with different mechanisms of action became available for treating CD in clinical practice. Vedolizumab – a gut-selective inhibitor of α4β7 integrin [5] – has been approved by EMA in 2014. Ustekinumab – an inhibitor of subunit p40 of interleukins 12 and 23 [6] – obtained approval by EMA in 2016. Finally, a recently approved therapy for refractory complex perianal CD is darvadstrocel, a preparation of human mesenchymal stem cells expanded from adult adipose tissue and designed for intralesional use during surgery for perianal disease [7].
In this evolving scenario, the American Gastroenterological Association [8] and the European Crohn’s and Colitis organisation [9] have recently published clinical practice guidelines on the use of therapeutics in CD. However, both documents took a broad view not limited to the use of biologics, which is the focus of the present guidelines. Furthermore, because economic and legal issues, as well as different viewpoints in general, may influence the indications for biologics, we believe that additional national recommendations are necessary to complement the existing international guidelines.
In 2019, the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) began a project to develop clinical guidelines, starting with the use of biologics and small molecule drugs in ulcerative colitis [10,11]. The current document presents the official recommendations on the use of biologics for managing CD. It deals with intestinal outcomes and does not provide indications for treating extra-intestinal manifestations, which will be the focus of a separate paper. These guidelines were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, which has become the reference method for developing high-quality, evidence-based recommendations for clinical practice [12]. They are accompanied by a technical review [13] that provides a detailed analysis of the evidence on which these recommendations are based. The work was fully funded by IG-IBD and did not receive any external funding.
LEGGI TUTTO https://doi.org/10.1016/j.dld.2023.01.155
