Despite recent advances in medical therapy, patients with Crohn’s Disease may still suffer disease progression requiring surgery and hospitalisation. It is increasingly recognised that early effective therapy is associated with improved patient outcomes and there is growing emphasis on early intervention, treat to target and tight control (TC) approaches [1]. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) programme highlighted the importance of targetting deep remission, defined as resolution of symptoms and objective resolution of inflammation on endoscopy [2]. The Effect of Tight Control Management on CD (CALM) study recently demonstrated that a TC approach in which therapy is escalated based on objective markers of inflammation [faecal calprotectin and C-reactive protein (CRP)], in addition to symptoms, is an effective strategy to achieve endoscopic and deep remission [3].
DRUG SURVIVAL OF ANTI-TNF AGENTS COMPARED WITH VEDOLIZUMAB AS A SECOND-LINE BIOLOGICAL TREATMENT IN INFLAMMATORY BOWEL DISEASE: RESULTS FROM NATIONWIDE SWEDISH REGISTERS
Sara Rundquist, Michael C Sachs, Carl Eriksson, Ola Olén, Scott Montgomery, Jonas Halfvarson, SWIBREG Study Group
The advent of monoclonal antibody therapy has propelled the management of Inflammatory Bowel Disease firmly into the biologic era, with numerous biologic therapies now licensed or in various stages of development.
Anti-tumour necrosis factor (TNF) agents such as infliximab [1, 2], adalimumab [3, 4] and golimumab [5]were the first biologics to be developed and have the greatest body of evidence for their effectiveness and safety in the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). The arrival of biosimilars has brought down costs and made treatment with anti-TNF more widespread, such that they are the most important first-line treatment option for moderate to severe IBD.
Crohn’s Disease is complicated by strictures in up to 30% of cases. Medical management with biologics is often suboptimal and surgical treatment is associated with postoperative complications and disease recurrence. Targeted therapy with endoscopic balloon dilatation (EBD) of strictures less than 5 cm has high rates of technical success (passage of endoscope through the stricture) but variable clinical success (relief of obstructive symptoms), with up to 25% of patients requiring surgery at one-year follow-up [1]. Removable fully covered metal stents are safe for the treatment of refractory strictures but the risk of stent migration is high [2].
Randomised clinical trial: high‐dose oral thiamine versus placebo for chronic fatigue in patients with quiescent inflammatory bowel disease (TARIF study)
Fatigue is a common yet poorly understood manifestation of Inflammatory Bowel Disease (IBD) and can occur independently of disease activity. A prospective cohort study of 326 IBD patients initiating biologic therapy (with infliximab, vedolizumab or ustekinumab) demonstrated fatigue was prevalent at baseline (63%)1. Whilst fewer patients reported fatigue with treatment (70% at week 14, 61% at week 30 and 61% at week 54), a third continued to experience fatigue despite achieving clinical remission. This is supported by other studies, where fatigue prevalence in quiescent disease was as high as 36% in Ulcerative Colitis (UC) and 41% in Crohn’s disease (CD)2.
In the last decade, research on the human gut microbiome and its influence on health and disease has taken flight. This has strengthened the belief that the underlying pathogenesis of Inflammatory Bowel Disease (IBD) involves an altered immune response to characteristic shifts in the composition of the gut microbiome.
Serum biomarkers identify patients who will develop inflammatory bowel diseases up to 5 years before diagnosis
Torres J, Petralia F, Sato T, et al.
Gastroenterology 2020;159:96–104.
Introduction
Inflammatory Bowel Disease is a chronic relapsing-remitting, immune-mediated condition with increasing prevalence globally [1]. Despite novel agents targeting different disease pathways, the likelihood of achieving sustained clinical remission and mucosal healing remains low [2]. One of the potential reasons may be that patients seek help and clinicians treat IBD once the disease is in its clinical phase. A sub-clinical phase of variable length may precede the symptoms that lead to a diagnosis and perhaps contribute to tissue damage which, once established, is difficult to reverse with currently available medical treatments.
In this study, Torres and colleagues set out to test the hypothesis that a pre-clinical phase of IBD may well be present and could be identified by proteomic markers [3].
Expression levels of 4 genes in colon tissue might be used to predict which patients will enter endoscopic remission after vedolizumab therapy for Inflammatory Bowel Diseases
Verstockt B, Verstockt S, Veny M, et al.
Clinical Gastroenterology and Hepatology. 2020;18:1142–51.
In the past few years the armamentarium of drugs used to treat Inflammatory Bowel Disease (IBD) has accelerated, with the emergence of new therapies targeting differing immune pathways (ustekinumab and tofacitinib) and lymphocyte trafficking (vedolizumab). Furthermore, a number of promising new drugs are on the horizon (JAK-1 inhibitors, IL23p19 antibodies and S1P inhibitors) [1, 2]. However, as the choice of drugs expands, so the uncertainty over which drug should be selected by the clinician also increases. Drug selection may be determined by a number of factors such as cost, mechanism of delivery (e.g. oral, intravenous or subcutaneous), presence of co-morbidities (such as malignancy or multiple sclerosis) and presence of extraintestinal manifestations. However, no drug is effective in all patients, with between 10% and 40% of patients suffering from primary and secondary loss of response [3–5].
Nowadays, IBD treatment not only targets symptomatic disease control but also aims to heal the intestinal mucosa [1] In Ulcerative Colitis (UC) there is mounting evidence that histological healing of the intestinal mucosa is associated with incremental benefit compared to endoscopic healing alone [2–8]. In a very recent meta-analysis of ten studies including 757 UC patients with complete endoscopic remission (Mayo Score 0 or equivalent) and with a minimum follow-up of >12 months, patients with histological remission had a 63% lower risk of clinical relapse (RR 0.37, 95% CI 0.24–0.56) than patients with ongoing microscopic inflammation [9].
Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn’s disease: retrospective long-term follow-up of the LIR!C trial
Stevens TW, Haasnoot ML, D’Haens GR, Buskens CJ, De Groof EJ, Eshuis EJ, Gardenbroek TJ, Mol B, Stokkers PCF, Bemelman WA, Ponsioen CY on behalf of the LIR!C study group
Lancet Gastroenterol Hepatol 2020 Jun 30;S2468-1253(20)30117-5. doi: 10.1016/S2468-1253(20)30117-5. Online ahead of print.
The positioning of medical therapies in the management of Crohn’s Disease (CD) continues to be debated [1] whilst surgery is reserved for cases with disease complications or failure of medical therapy. The LIR!C trial [2] provided evidence for surgical resection as an alternative to infliximab (IFX) in the management of localised terminal ileitis, a common presentation of CD [3].
Briefly, the LIR!C trial reported quality of life scores (IBDQ) among 143 adult patients with terminal ileitis (<40 cm) who underwent randomisation to IFX induction/maintenance or ileocaecal resection. Patients were recruited from 29 secondary and tertiary Dutch and British centres. Exclusion criteria included non-inflammatory disease, prestenotic dilatation, abscess and previous surgery. Inclusion criteria included failing at least three months of conventional therapy [immunomodulator (IM) and/or corticosteroid (CS)] [2]
First introduced by Svartz in 1942, 5-aminosalicylates (5-ASAs) are a well-established and effective first-line therapy for the induction and maintenance of remission in patients with mild-to-moderate Ulcerative Colitis (UC). They remain the most frequently prescribed medication for UC and are known to be effective and well tolerated [1]. Between 87% and 98% of UC patients receive 5-ASA treatment within the first year of diagnosis and 60%–87% continue on this treatment at ten years [2, 3].
Escalation to anti-metabolites (thiopurines or methotrexate) and/or biologic or small molecule therapy is often required for UC patients with a more aggressive disease course. Whilst it is now accepted that discontinuing 5-ASA therapy when escalating to a biologic is not associated with adverse outcomes, less is known about the therapeutic benefit of continuation of 5-ASAs with an antimetabolite [2, 4].
Singh et al conducted a retrospective cohort study to evaluate the pattern of 5-ASA use in patients with UC following escalation to an antimetabolite. The study evaluated patients escalated to antimetabolite therapy (stopping 5-ASA vs short-term 5-ASA use for <6 months vs persistent 5-ASA use for >6 months) and compared the risk of clinically important complications based on the pattern of 5-ASA use in these patients. They hypothesised that continuing 5-ASA therapy would not be more beneficial than stopping it.
