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Management of inflammatory bowel disease in adults: BSG Guidelines


Management of inflammatory bowel disease in adults: BSG Guidelines

British Society of Gastroenterology has released 2019 consensus guidelines on the management of inflammatory bowel disease in adults. The new guidelines have appeared in the Journal Gut.

Ulcerative colitis and Crohn’s disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients.

 Following are the major recommendations:

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  • Where ulcerative colitis is diagnosed by sigmoidoscopy, we recommend a full ileocolonoscopy to delineate disease extent, severity of inflammation and to exclude Crohn’s disease (GRADE: strong recommendation, very low-quality evidence. Agreement: 100%).
  • We suggest that symptomatic remission combined with mucosal healing should be the target of medical therapy in ulcerative colitis (GRADE: weak recommendation, very low-quality evidence. Agreement: 95.7%).
  • We recommend that mild to moderate ulcerative colitis should be managed with oral 5-ASA 2–3 g/day (GRADE: strong recommendation, high-quality evidence). We recommend the addition of 5-ASA enemas, rather than oral treatment alone (GRADE: strong recommendation, high-quality evidence. Agreement: 95.6%).
  • We suggest that ulcerative colitis patients flaring on 5-ASA therapy should receive dose escalation to 4–4.8 g/day orally alongside 5-ASA enemas (GRADE: weak recommendation, low-quality evidence. Agreement: 82.2%).
  • We recommend that ulcerative colitis patients treated with 5-ASA should be monitored for the development of nephrotoxicity, with baseline renal function, repeated after 2–3 months, and then annually (GRADE: strong recommendation, very low-quality evidence. Agreement: 90.9%).
  • We recommend that patients with mild to moderate ulcerative colitis in whom 5-ASA induction therapy fails or is not tolerated should be treated with oral prednisolone (GRADE: strong recommendation, high-quality evidence). We recommend that topically-acting oral corticosteroids such as budesonide MMX (GRADE: strong recommendation, moderate-quality evidence) and we suggest that beclomethasone dipropionate (GRADE: weak recommendation, moderate-quality evidence) can be used as alternative treatments for those wishing to avoid systemic corticosteroids (Agreement: 93.2%).
  • We recommend that moderate to severe ulcerative colitis should be treated with oral corticosteroids such as prednisolone 40 mg daily weaning over 6–8 weeks (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We recommend that oral 5-ASA should be the standard maintenance medical therapy in ulcerative colitis (GRADE: strong recommendation, high-quality evidence). We recommend that the choice of formulation should consider patient preference, likely adherence and cost. Once-daily dosing is effective (GRADE: strong recommendation, high-quality evidence) and may improve adherence (Agreement: 100%).
  • We recommend that ulcerative colitis patients on maintenance therapy with high-dose mesalazine, who required two or more courses of corticosteroids in the past year, or who become corticosteroid-dependent or refractory, require treatment escalation with thiopurine (GRADE: strong recommendation, moderate-quality evidence), anti-TNF therapy (GRADE: strong recommendation, high-quality evidence), vedolizumab (GRADE: strong recommendation, high-quality evidence) or tofacitinib (GRADE: strong recommendation, high-quality evidence). The choice of drug should be determined by clinical factors, patient choice, cost, likely adherence and local infusion capacity (Agreement: 96.6%).
  • We recommend that vedolizumab can be used in the induction and maintenance of remission of ulcerative colitis in patients where anti-TNF treatment has failed (GRADE: strong recommendation, high-quality evidence. Agreement: 97.7%).
  • We recommend that tofacitinib can be used in the induction and maintenance of remission of ulcerative colitis in patients where anti-TNF treatment has failed (GRADE: strong recommendation, high-quality evidence. Agreement: 91.1%).
  • We recommend that mild or moderately active ulcerative proctitis should be treated with a 1 g 5-ASA suppository (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We suggest that patients with ulcerative proctitis who do not respond or are intolerant to 5-ASA suppositories and oral 5-ASA may be switched to corticosteroid suppositories (GRADE: weak recommendation, low-quality evidence. Agreement: 84.8%).
  • We suggest that refractory ulcerative proctitis may require treatment with corticosteroids, immunomodulators and/or biological therapy (GRADE: weak recommendation, very low-quality evidence. Agreement: 95.5%).
  • We recommend that adult patients with acute severe ulcerative colitis (ASUC) (defined by the modified Truelove and Witts criteria as >6 bloody stools per day and systemic toxicity with at least one of: temperature >37.8°C, pulse >90 bpm, haemoglobin <105 g/L or C-reactive protein >30 mg/L) or adolescents with a Paediatric Ulcerative Colitis Activity Index (PUCAI) score of 65 or more should be admitted to hospital for assessment and intensive management (GRADE: strong recommendation, low-quality evidence. Agreement: 100%).
  • We recommend that patients presenting with possible acute severe colitis should have urgent inpatient assessment and blood tests (FBC, CRP, U&E, LFTs and magnesium), stool culture, Clostridium difficile assay, radiological imaging (AXR or CT) and flexible sigmoidoscopy (GRADE: strong recommendation, very low-quality evidence. Agreement: 97.9%).
  • We recommend that patients with ASUC should be treated with high-dose intravenous corticosteroids such as methylprednisolone 60 mg daily or hydrocortisone 100 mg 6-hourly (GRADE: strong recommendation, high-quality evidence) and should receive prophylactic low-molecular weight heparin (GRADE: strong recommendation, moderate-quality evidence. Agreement: 97.8%).
  • We recommend that patients with ASUC failing to respond by day 3, as judged by a suitable scoring system, should be treated with rescue therapy in the form of intravenous infliximab or ciclosporin for patients who have not previously failed thiopurine therapy (GRADE: strong recommendation, high-quality evidence. Agreement: 97.8%).
  • We suggest that patients treated with infliximab for ASUC who have not responded sufficiently to a 5 mg/kg dose 3–5 days after first infusion should be treated with an accelerated induction regimen after colorectal surgical review to determine whether emergency colectomy is required (GRADE: weak recommendation, low-quality evidence. Agreement: 95.7%).
  • We recommend that patients with ASUC who have not responded within 7 days of rescue therapy with infliximab or ciclosporin, or those with a deterioration or complications before that time (including toxic megacolon, severe haemorrhage or perforation) require subtotal colectomy and ileostomy, with preservation of the rectum (GRADE: strong recommendation, very low-quality evidence. Agreement: 97.4%).
  • We suggest that surgical resection of the colon and rectum in ulcerative colitis should be offered to patients who have chronic active symptoms despite optimal medical therapy. Ileoanal pouch reconstruction or end ileostomy provide equivalently good quality of life, and are a matter of patient choice (GRADE: weak recommendation, very low-quality evidence. Agreement: 94.4%).
  • We suggest that pouch surgery should be performed in specialist high-volume referral centres (GRADE: weak recommendation, low-quality evidence. Agreement 97.4%).
  • We recommend that a 2 week course of ciprofloxacin or metronidazole is the first-line treatment of acute pouchitis (GRADE: strong recommendation, low-quality evidence). We suggest that ciprofloxacin is better tolerated and may be more effective than metronidazole (GRADE: weak recommendation, low-quality evidence. Agreement: 97.2%).
  • We suggest that chronic pouchitis may be treated with a combination of antibiotics (ciprofloxacin, metronidazole, tinidazole, rifaximin), oral budesonide or oral beclomethasone (GRADE: weak recommendation, very low-quality evidence. Agreement: 85.7%).
  • Chronic refractory pouchitis not responding to antibiotics or locally-acting corticosteroids should be reassessed to consider other factors, and if excluded, we suggest that patients may be offered biologics (GRADE: weak recommendation, low-quality evidence. Agreement: 90.9%).
  • Restorative proctocolectomy with an IPAA does not completely abolish the risk of neoplasia. We suggest that patients with high-risk factors may be offered surveillance pouchoscopy although it is unclear how frequently this should be performed. Low-risk patients do not require surveillance (GRADE: weak recommendation, very low-quality evidence. Agreement: 94.4%)
  • We suggest that adult patients with Crohn’s disease do not routinely require upper gastrointestinal endoscopy as part of the diagnostic evaluation unless they have upper gastrointestinal symptoms (GRADE: weak recommendation, very low-quality evidence. Agreement: 91.1%).
  • We suggest that cross-sectional imaging, specifically MRI, CT and ultrasound, have largely replaced conventional barium fluoroscopic and nuclear medicine techniques and have the advantage of evaluating both luminal and extraluminal disease. Emphasis should be placed on MR enterography and ultrasound as they do not expose patients to ionising radiation (GRADE: weak recommendation, moderate-quality evidence. Agreement: 97.9%).
  • We suggest that, while there is no clear evidence of diagnostic superiority for one cross-sectional imaging modality over another for stricture diagnosis, emphasis should be placed on techniques that do not expose patients to ionising radiation. For colonic or anastomotic strictures, endoscopy and biopsy should be performed to assess and exclude cancer, provided the stricture is accessible and endoscopy deemed safe (GRADE: weak recommendation, very low-quality evidence. Agreement: 100%).
  • We suggest that capsule endoscopy has greater sensitivity for mucosal small bowel Crohn’s disease than radiological imaging techniques and can generally be performed where inflammatory small bowel disease is still suspected despite normal or equivocal cross-sectional imaging. Minor changes found at capsule endoscopy may be insufficient in isolation to diagnose Crohn’s disease, particularly with recent NSAID use (GRADE: weak recommendation, moderate-quality evidence. Agreement 90.9%).
  • The risk of capsule retention is low in suspected Crohn’s disease patients without symptoms suggestive of stricture. However, when obstructive symptoms are present, or in known stricturing Crohn’s disease where capsule endoscopy is indicated, we suggest that patency capsule should precede capsule endoscopy (GRADE: weak recommendation, low-quality evidence. Agreement: 93.5%).
  • We recommend that mild to moderate ileocaecal Crohn’s disease can be treated with ileal-release budesonide 9 mg once daily for 8 weeks to induce remission (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We recommend that active Crohn’s colitis can be treated with an 8-week course of systemic corticosteroids to induce remission (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We suggest that Exclusive Enteral Nutrition (EEN) may be used to induce remission in mild to moderate Crohn’s disease patients where avoidance of corticosteroid is desired, and in those who are motivated to adhere strictly to EEN for up to 8 weeks (GRADE: weak recommendation, very low-quality evidence. Agreement: 86.4%).
  • We recommend that polymeric feeds are as effective as elemental or semi-elemental feeds in treatment of Crohn’s disease, and improve adherence (GRADE: strong recommendation, very low-quality evidence. Agreement: 86.7%).
  • We suggest that laparoscopic resection should be considered in localised ileocaecal Crohn’s disease for those failing or relapsing after initial medical therapy, or in those preferring surgery to continuation of drug therapy (GRADE: weak recommendation, moderate-quality evidence. Agreement: 93.5%).
  • We recommend that moderate to severely active uncomplicated luminal Crohn’s disease should be treated initially with systemic corticosteroids (GRADE: strong recommendation, high-quality evidence), but we suggest that those with extensive disease or other poor prognostic features should be considered for early introduction of biological therapy (GRADE: weak recommendation, moderate-quality evidence. Agreement: 86.7%).
  • We recommend that systemic or locally acting corticosteroids should be avoided as maintenance therapy in Crohn’s disease due to toxicity and lack of efficacy (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We recommend that for patients with moderate to severe Crohn’s disease responding to prednisolone, early introduction of maintenance therapy with thiopurines (GRADE: strong recommendation, low-quality evidence) or methotrexate (GRADE: strong recommendation, moderate-quality evidence) should be considered to minimise risk of flare as prednisolone is withdrawn (Agreement: 93.3%).
  • We recommend that azathioprine or mercaptopurine can be used as monotherapy in the maintenance of remission in Crohn’s disease (GRADE: strong recommendation, low-quality evidence. Agreement: 100%).
  • We suggest that methotrexate may be used for the maintenance of remission of Crohn’s disease, and the dose should be at least 15 mg weekly. Subcutaneous administration has better bioavailability than oral, particularly at higher doses (GRADE: weak recommendation, moderate-quality evidence. Agreement: 88.4%).
  • We recommend that mesalazine is not used for induction or maintenance of remission in Crohn’s disease (GRADE: strong recommendation, moderate-quality evidence. Agreement: 97.7%).
  • We recommend that patients refractory to immunomodulator therapy despite dose optimisation should be considered for biological therapy. Choice between anti-TNF therapy, ustekinumab and vedolizumab should be made on an individual basis, considering patient preference, cost, likely adherence, safety data and speed of response to the drug (GRADE: strong recommendation, very low-quality evidence. Agreement: 95.7%).
  • We recommend that combination therapy of infliximab with a thiopurine should be used as it is more effective than monotherapy infliximab in induction and maintenance of remission in active Crohn’s disease (GRADE: strong recommendation, high-quality evidence. Agreement: 97.7%).
  • We suggest that combination therapy of infliximab with methotrexate therapy may be used in Crohn’s disease to reduce immunogenicity (GRADE: weak recommendation, moderate-quality evidence. Agreement: 90.5%).
  • We recommend that in Crohn’s disease, vedolizumab can be used in both anti-TNF naïve patients and in those where anti-TNF treatment fails. Choice of treatment in biologics-naïve patients should be individualised (GRADE for induction therapy: strong recommendation, moderate-quality evidence; GRADE for maintenance therapy: strong recommendation, high-quality evidence. Agreement: 95.5%).
  • We recommend that ustekinumab can be used in the induction and maintenance of remission of Crohn’s disease, both in anti-TNF naïve patients and in those where anti-TNF treatment fails. No direct comparison data are available with other biological therapies (GRADE: strong recommendation, high-quality evidence. Agreement: 97.7%).
  •  We suggest that, where a switch from anti-TNF therapy to a different drug class is required in Crohn’s disease, the choice to use vedolizumab or ustekinumab may be made on an individual basis. Factors to be included in the decision-making process should include patient preference, cost, likely adherence, safety data and speed of response to the drug. The potential for surgery as an alternative to further drug therapy should also be considered (GRADE: weak recommendation, very low-quality evidence. Agreement: 97.8%).
  • Patients with Crohn’s disease treated with a biological therapy in optimal dose who remain corticosteroid-dependent (particularly if on triple immunosuppression with immunomodulator therapy) are at significant risk of opportunistic infections. We recommend that alternative medical treatments or surgery should be explored (GRADE: strong recommendation, moderate-quality evidence. Agreement: 97.8%).
  • We recommend that leucocyte apheresis is not used for active Crohn’s disease due to lack of efficacy (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • Patients with jejunal or extensive small bowel disease have a worse prognosis. We suggest that they may be considered for early use of biological therapy, and should have nutritional assessment and support (GRADE: weak recommendation, very low-quality evidence. Agreement: 100%).
  • We suggest that mild gastroduodenal Crohn’s disease may be treated with proton pump inhibitors. We suggest that moderate or severe disease may also require treatment with corticosteroids, and other immunosuppressive or biological therapies as for Crohn’s disease elsewhere in the gut (GRADE: weak recommendation, very low-quality evidence. Agreement: 92.7%).
  • We suggest that mild oesophageal Crohn’s disease may be treated with proton pump inhibitors. Nutritional assessment and support is essential. A short course of corticosteroids may be required if symptoms worsen, but early anti-TNF therapy should be considered for ongoing moderate to severe disease. Oesophageal dilatation should be used for strictures, and surgery is a last resort for disease refractory to all medical therapy (GRADE: weak recommendation, very low-quality evidence. Agreement: 97.6%).
  • We suggest that patients presenting with features of orofacial granulomatosis (OFG) and gastrointestinal symptoms, raised inflammatory markers or raised faecal calprotectin should have the gastrointestinal tract investigated for inflammation (GRADE: weak recommendation, very low-quality evidence. Agreement: 100%).
  • We recommend that strictureplasty is an alternative to resection in patients with small bowel Crohn’s disease strictures shorter than 10 cm, and is useful where there are multiple strictures or a need to preserve gut length. Longer strictures can be treated using non-standard strictureplasty techniques (GRADE: strong recommendation, very low-quality evidence. Agreement: 97.3%).
  • We suggest that balloon dilatation is an appropriate treatment for ileocolonic anastomotic strictures less than 4 cm in length, without sharp angulation and with non-penetrating disease, although the majority will require repeated dilatation. Endoscopically accessible ileal strictures are also amenable to balloon dilation, but complication rates and recurrence rates are higher (GRADE: weak recommendation, low-quality evidence. Agreement: 94.4%).
  • We suggest that intra-abdominal abscesses complicating Crohn’s disease may be treated initially with intravenous antibiotics and where possible radiological drainage. Surgical drainage may be required but immediate resection should be avoided (GRADE: weak recommendation, very low-quality evidence. Agreement: 91.9%).
  • We recommend that enterovaginal and enterovesical fistulae should be managed jointly with medical control of inflammation and surgical resection (GRADE: strong recommendation, very low-quality evidence. Agreement: 100%).
  • We suggest that low volume enterocutaneous fistulae may be controlled with immunomodulator and biological therapy. High-volume fistulae usually require surgery to achieve symptom control (GRADE: weak recommendation, very low-quality evidence. Agreement: 100%).
  • We suggest that anti-TNF therapy may be used to control inflammation or maintain remission in the setting of non-perianal fistulising Crohn’s disease (GRADE: weak recommendation, low-quality evidence. Agreement: 94.6%).
  • We recommend that anti-TNF therapy should only be started after abscesses have been treated with antibiotics and, where possible, drainage (GRADE: strong recommendation, very low-quality evidence. Agreement: 94.9%).
  • We recommend that pelvic MRI is used as an important adjunct to clinical assessment and examination under anaesthesia (by an experienced surgeon) in evaluation of fistulising perianal Crohn’s disease. Depending on local availability and expertise, endoanal ultrasound may also be used (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We recommend that examination under anaesthesia should include an assessment of the rectal mucosa as the presence of proctitis is associated with lower rates of fistula healing in perianal Crohn’s disease (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We recommend that setons should be placed to prevent re-accumulation of perianal sepsis in fistulising Crohn’s disease (GRADE: strong recommendation, moderate-quality evidence). The optimal timing of seton removal is uncertain (Agreement: 97.1%).
  • We recommend that infliximab is used as the first-line biological therapy for complex perianal fistulae, and should be started as soon as adequate drainage of sepsis is achieved (GRADE: strong recommendation, high-quality evidence. Agreement: 100%).
  • We recommend that faecal stream diversion can be used in patients with severe perianal Crohn’s disease refractory to medical therapy. Patients should be counselled that rates of subsequent successful reversal are low and proctectomy may ultimately be required (GRADE: strong recommendation, low-quality evidence. Agreement: 100%).
  • We suggest that, in the event of symptomatic recurrence following ileocolonic resection for Crohn’s disease, an assessment of mucosal inflammation may be performed with ileocolonoscopy. Faecal calprotectin and/or cross-sectional imaging may be used if ileocolonoscopy is not possible or acceptable, but may not be sensitive enough to detect localised inflammation (GRADE: weak recommendation, low-quality evidence. Agreement: 97.4%).
  • We recommend that, following ileal resection, Crohn’s disease patients with diarrhoea suggestive of bile acid malabsorption should be given a therapeutic trial of a bile acid sequestrant such as colestyramine or colesevelam (GRADE: strong recommendation, moderate-quality evidence). A SeHCAT study can be considered for failed response to therapy or if the diagnosis is unclear (Agreement: 97.2%).
  • We recommend that all patients smoking after intestinal resection for Crohn’s disease should be actively encouraged to stop (GRADE: strong recommendation, moderate-quality evidence. Agreement: 100%).
  •  We suggest that, following ileocolonic resection for Crohn’s disease, ileocolonoscopy may be performed at 6 months to assess the neoterminal ileum in order to consider treatment escalation if mucosal inflammation (Rutgeerts i2 or above) (GRADE: weak recommendation, low-quality evidence). If the anastomosis is not within reach of endoscopic examination, then cross-sectional imaging with MR enterogram may be performed (Agreement: 89.2%).
  • We suggest that Crohn’s disease patients with significant risk factors for disease recurrence following ileocolonic resection (particularly smoking) or with recurrent disease at 6 months post-surgery colonoscopy may be started on thiopurines (GRADE: weak recommendation, low-quality evidence) or anti-TNF therapy (GRADE: weak recommendation, low-quality evidence. Agreement: 94.4%).
  • We recommend that mesalazine should not be given to prevent recurrence after ileocolonic Crohn’s disease resection (GRADE: strong recommendation, moderate-quality evidence. Agreement: 97.2%).
  • We recommend that the differential diagnosis of tuberculosis should be considered in patients with suspected ileocaecal Crohn ’s disease, particularly in patients born in or who have lived for extended periods in endemic areas or have other risk factors for infection (GRADE: strong recommendation, very low-quality evidence. Agreement: 97.8%).
  • We recommend that all patients presenting with acute flares of colitis should have stool cultures for entero-invasive bacterial infections and stool Clostridium difficile assay (GRADE: strong recommendation, low-quality evidence). Microscopy and culture for amoebic or Shigella dysentery should be performed in patients with relevant travel history (Agreement: 93.5%).
  • We suggest that Clostridium difficile infection in acute severe ulcerative colitis is associated with significantly increased risk of colectomy and should be treated with oral vancomycin (GRADE: weak recommendation, low-quality evidence. Agreement: 93.2%).
  • We suggest that patients with moderate to severe colitis, particularly those with corticosteroid-refractory disease, should have colonic biopsies to look for cytomegalovirus disease by H&E staining, and preferably also immunohistochemistry or quantitative tissue PCR (GRADE: weak recommendation, low-quality evidence. Agreement: 93.3%).
  • We suggest that CMV reactivation in the colonic mucosa of patients hospitalised with an exacerbation of ulcerative colitis or Crohn’s colitis may be treated by intravenous ganciclovir 5 mg/kg twice daily while continuing conventional therapy with corticosteroids or rescue medication with infliximab or ciclosporin (GRADE: strong recommendation, very low-quality evidence). In rare cases with systemic disease (meningo-encephalitis, pneumonitis, hepatitis or oesophagitis), all immunosuppressive therapy should be stopped while CMV is treated (GRADE: weak recommendation, very low-quality evidence). (Agreement: 88.4%).
  • We suggest that blood tests for thiopurine methyltransferase status and screen for HBV, HCV and HIV (and VZV if no history of chicken pox, shingles or varicella vaccination) may be arranged once diagnosis is confirmed for all Crohn’s disease and moderate to severe ulcerative colitis patients (GRADE: weak recommendation, very low-quality evidence. Agreement: 88.9%).
  • We recommend that IBD patients commencing immunomodulators or biologics treatment should undergo screening for HBV, HCV and HIV (and VZV if no history of chicken pox, shingles or varicella vaccination), unless screened already at time of diagnosis (GRADE: strong recommendation, very low-quality evidence. Agreement: 88.9%).
  • We recommend that prior to commencing anti-TNF therapy, IBD patients should be screened for tuberculosis (TB) using a combination of clinical risk stratification, chest x-ray and interferon-gamma release assays (IGRAs) (GRADE: strong recommendation, low-quality evidence. Agreement: 97.8%).
  • We suggest that IBD patients who have travelled for long periods or lived in endemic areas may be at increased risk of parasitic infections, and may have Strongyloides serology, and eosinophil count checked prior to commencing anti-TNF therapy (GRADE: weak recommendation, very low-quality evidence. Agreement: 90.9%).
  • We recommend that a vaccination history should be obtained and vaccinations updated for all patients with Crohn’s disease, those with moderate to severe ulcerative colitis at diagnosis, and prior to commencing immunomodulator or biologics in all patients. Live vaccinations may be given at least 4 weeks before starting and at a minimum of 3 months after stopping, but not while receiving immunosuppressive therapy (GRADE: strong recommendation, very low-quality evidence. Agreement: 93%).
  • We recommend that IBD patients receiving immunomodulators or biologics should receive influenza vaccination each autumn, and pneumococcal vaccination with a booster after 5 years (GRADE: strong recommendation, very low-quality evidence. Agreement: 95.5%).
  • We recommend that all IBD patients considered for thiopurine therapy should have assessment of thiopurine methyltransferase (TPMT) status (GRADE: strong recommendation, moderate-quality evidence. Agreement: 100%).
  • We recommend that thiopurines should be avoided in patients with low TPMT activity. The dose of thiopurine should be reduced to 50% in those with intermediate thiopurine activity. Daily dosage should also be reduced in patients with significant renal impairment (GRADE: strong recommendation, moderate-quality evidence. Agreement: 100%).
  • We recommend that women with IBD commencing thiopurine therapy should be advised to participate in a national cervical screening programme (GRADE: strong recommendation, very low-quality evidence. Agreement: 95.7%).
  • Thiopurine metabolites (TGN and MeMP) can be used to optimise drug dosing. We suggest that metabolite monitoring may be used for those with inadequate response to therapy or toxicity, but should not be a substitute for routine monitoring blood tests (GRADE: weak recommendation, low-quality evidence. Agreement: 92.9%).
  • We suggest that low-dose thiopurines (25–33% of usual dose) used in combination with allopurinol 100 mg may be considered in patients with thiopurine hepatotoxicity, nausea or flu-like symptoms, or those who are hypermethylators (GRADE: weak recommendation, low-quality evidence. Agreement: 81.4%).
  • We recommend that IBD patients initiating thiopurine or methotrexate therapy should have baseline FBC, U&E and LFT measurement, with monitoring of these bloods at least at weeks 2, 4, 8 and 12, and then at least 3-monthly with monitoring for side effects (GRADE: strong recommendation, low-quality evidence. Agreement: 100%).
  • We recommend that, due to teratogenic and embryotoxic effects of methotrexate, prior to conception women should discontinue methotrexate for 6 months (GRADE: strong recommendation, low-quality evidence). If patients become pregnant on methotrexate then the drug should be discontinued and high dose folic acid (15 mg daily) provided for at least 6 weeks. We suggest that men taking methotrexate may not need to discontinue treatment prior to conception (GRADE: weak recommendation, low-quality evidence. Agreement: 92.7%).
  • We recommend that biosimilar infliximab may be used for IBD patients starting treatment (GRADE: strong recommendation, low-quality evidence). We recommend that patients already on originator infliximab can be switched to biosimilar infliximab if in stable response or remission (GRADE: strong recommendation, moderate-quality evidence. Agreement: 97.7%).
  • We suggest that treatment options for failure of initial anti-TNF therapy (increase dose, shorten dosage interval, switch to alternative anti-TNF, or switch to different drug class) may be informed by the clinical context and by measurement of serum drug and anti-drug antibody concentrations (GRADE: weak recommendation, low-quality evidence. Agreement: 97.7%).
  • We suggest that patients with secondary loss of response to anti-TNF therapy may have serum drug and anti-drug antibody concentrations measured to inform appropriate changes in treatment (GRADE: weak recommendation, moderate-quality evidence. Agreement: 97.6%).
  • We suggest that pretreatment screening and blood monitoring of therapy on vedolizumab and ustekinumab should at present follow recommendations for anti-TNF drugs due to insufficient long-term safety data at this time to recommend an alternative algorithm (GRADE: weak recommendation, very low-quality evidence. Agreement: 95.3%).
  • We suggest that IBD patients in prolonged remission on thiopurines, and who have mucosal healing, may stop the drug after discussion of risks and benefits and considering patient preference. Reintroduction if relapse occurs is usually successful (GRADE: weak recommendation, low-quality evidence. Agreement: 95.3%).
  • We suggest that anti-TNF therapy may be withdrawn in patients with prolonged corticosteroid-free remission and mucosal healing. Retreatment in the event of relapse is usually successful, but there is insufficient evidence about which clinical factors predict relapse after withdrawal and decisions should be individualised (GRADE: weak recommendation, very low-quality evidence. Agreement: 93.2%).
  • We suggest that patients in whom anti-TNF therapy is withdrawn should be observed for evidence of relapse. Monitoring of faecal calprotectin may be helpful in this context as levels may rise before clinical relapse occurs (GRADE: weak recommendation, low-quality evidence. Agreement: 97.9%).
  • We recommend that prolonged corticosteroid therapy is harmful and should be minimised by specialist intervention and involvement with the multidisciplinary team to explore other treatment options (GRADE: strong recommendation, moderate-quality evidence. Agreement: 97.8%).
  • We recommend that all patients receiving a course of corticosteroids for a disease flare should receive an intake of 800–1000 mg/day calcium and 800 IU/day vitamin D (GRADE: strong recommendation, very low-quality evidence). This can be achieved by administration of oral calcium and vitamin D supplements while on corticosteroids, or vitamin D only if dietary calcium intake is adequate. Lifestyle modification advice including regular physical exercise and smoking cessation should also be provided (Agreement: 90.9%).
  • We recommend that patients starting corticosteroids should be assessed for risk of osteoporosis. Those at high risk should be started on bisphosphonate therapy at the onset of corticosteroid therapy (GRADE: strong recommendation, high-quality evidence), after ensuring adequate calcium intake and supplementing vitamin D (Agreement: 90.7%).
  • We suggest that adult IBD patients on triple immunosuppression and using more than 20 mg prednisolone may be offered prophylactic antibiotics for Pneumocystis jirovecii (co-trimoxazole oral 960 mg three times weekly or 480 mg daily) (GRADE: weak recommendation, very low-quality evidence. Agreement: 85.7%).
  • We recommend that IBD patients who are malnourished or at risk of malnutrition should have relevant screening blood tests to assess for macronutrient and micronutrient deficiencies. This may include measurement of iron stores, vitamin B12, folate, vitamins A, C, D and E, potassium, calcium, magnesium, phosphate, zinc and selenium (GRADE: strong recommendation, very low-quality evidence. Agreement: 93.6%).
  • We suggest that vitamin D levels should be measured and deficiency corrected in Crohn’s disease and ulcerative colitis (GRADE: weak recommendation, very low-quality evidence. Agreement: 86.7%).
  • We suggest that a low FODMAP diet may be used to treat functional bowel symptoms in IBD patients (GRADE: weak recommendation, low-quality evidence. Agreement: 84.4%).
  • We recommend that IBD patients should have assessment and optimisation of their physical condition prior to elective surgery. This should include appropriate imaging to determine disease extent and complications; radiological drainage of abscesses and treatment of sepsis; correction of anaemia; treatment of malnutrition and physical mobilisation (GRADE: strong recommendation, very low-quality evidence. Agreement: 97.3%).
  • We recommend that prior to surgery all IBD patients should have their nutritional status assessed and if at risk of malnutrition should receive nutritional support (oral nutritional supplements or enteral or parenteral nutrition if required) (GRADE: strong recommendation, very low-quality evidence. Agreement: 97.3%).
  • We suggest that patients with penetrating or stricturing Crohn’s disease, or those who are malnourished, may benefit from exclusive or partial enteral nutrition for at least 6 weeks preoperatively (GRADE: weak recommendation, very low-quality evidence. Agreement: 97.2%).
  • We recommend that prior to elective surgery for Crohn’s disease or ulcerative colitis, corticosteroids should be stopped or dose minimised wherever possible to reduce risk of postoperative complications (GRADE: strong recommendation, low-quality evidence. Agreement: 94.6%).
  • We recommend that IBD patients who have been on oral corticosteroids for more than 4 weeks prior to surgery should receive an equivalent intravenous dose of hydrocortisone while nil by mouth in the perioperative period (GRADE: strong recommendation, moderate-quality evidence. Agreement: 100%).
  • We recommend that patients with ulcerative colitis should not be considered for pouch surgery while taking corticosteroids (GRADE: strong recommendation, very low-quality evidence. Agreement: 94.1%).
  • We recommend that, for patients aged 16–40 presenting in primary care with chronic diarrhoea and symptoms that may be consistent with either IBD or IBS, faecal calprotectin is a useful screening tool with a high negative predictive value. If significantly elevated, patients should have an infective cause excluded and be referred for further investigation (GRADE: strong recommendation, moderate-quality evidence. Agreement: 97.9%).
  • We suggest that, in IBD patients where it is unclear if symptoms are due to ongoing inflammation or other non-inflammatory causes (such as bile acid malabsorption, functional bowel disorder or short bowel), faecal calprotectin measurement may be used to provide evidence of mucosal inflammation (GRADE: weak recommendation, low-quality evidence. Agreement: 97.8%).
  • We suggest that faecal calprotectin is a validated biomarker for endoscopic and histological disease activity. It may therefore be a useful non-invasive parameter to inform decisions on treatment escalation or de-escalation (GRADE: weak recommendation, moderate-quality evidence. Agreement: 100%).
  • We recommend that IBD patients should be routinely asked about medication adherence because non-adherence is common and results in worse outcomes. Risk factors include young age, psychological distress, patient beliefs and discordance between patient and health professional GRADE: strong recommendation, moderate-quality evidence. Agreement: 100%).
  • We recommend that IBD patients at risk of non-adherence should be offered a variety of means to improve adherence, such as regimen simplification, reminder aids and additional support and education (GRADE: strong recommendation, low-quality evidence. Agreement: 97.8%).
  • We recommend that smokers with Crohn’s disease should be encouraged to stop, as smokers have a higher risk of disease flare, a higher incidence of surgery and a higher risk of postoperative recurrent disease (GRADE: strong recommendation, low-quality evidence. Agreement: 100%).
  • Ulcerative colitis patients who continue to smoke cigarettes should be encouraged to stop. There is an increased risk of flare after stopping, and patients should be made aware of this. We suggest that they are informed that an increase in medication may be required to control their disease (GRADE: weak recommendation, very low-quality evidence. Agreement: 95.7%).
  • We suggest that in patients with IBD, psychological therapies including cognitive behavioural therapy, hypnotherapy and mindfulness meditation may be offered to interested patients, particularly those with psychological symptoms, as an adjunctive therapy to improve symptom control and quality of life (GRADE: weak recommendation, very low-quality evidence. Agreement: 91.1%).
  •  We suggest that psychological interventions may be useful for IBD patients with pain where no physical cause can be found, and may be discussed and offered as adjunctive therapy (GRADE: weak recommendation, very low-quality evidence. Agreement: 93.5%).
  • We suggest that IBD patients with disabling fatigue in whom no correctable metabolic deficiency or active disease is found, or where fatigue persists despite addressing these factors, may be directed to non-pharmacological therapies. Patients may be interested in supportive psychotherapy, stress management or graded exercise (GRADE: weak recommendation, low-quality evidence. Agreement: 89.1%).
  • We recommend that the mainstay of symptom relief for IBD-associated arthropathy which is related to IBD activity should be through control of intestinal inflammation, physiotherapy and simple analgesia (GRADE: strong recommendation, very low-quality evidence. Agreement: 100%).
  • We recommend that for IBD-related arthropathy which is not related to IBD activity, rheumatology referral, physiotherapy and simple analgesia should be offered (GRADE: strong recommendation, very low-quality evidence. Agreement: 93.6%).
  • We suggest that short-term use of NSAIDs is safe if IBD is in remission, but long-term use or use in active disease carries more risk of worsening IBD symptoms. There is no high-quality evidence that COX-2 inhibitors are safer than non-selective agents (GRADE: weak recommendation, very low-quality evidence. Agreement: 81.4%).
  • We suggest that faecal microbiota transplantation (FMT) shows some evidence of benefit in ulcerative colitis and should be used in the context of clinical trials until further high-quality evidence clarifies the potential for benefit and optimal administration protocol (GRADE: weak recommendation, moderate-quality evidence. Agreement: 93.3%).
  • We recommend that IBD patients with colonic disease should be offered ileocolonoscopy 8 years after symptom onset to screen for neoplasia, to determine disease extent and decide on the frequency of ongoing surveillance (GRADE: strong recommendation, very low-quality evidence. Agreement: 89.1%).
  • We recommend that patients with ulcerative colitis or IBD-U with left-sided or more extensive disease should be advised to take mesalazine in doses of at least 2 g daily to reduce risk of colorectal cancer (GRADE: strong recommendation, moderate-quality evidence. Agreement: 95.5%).
  • We suggest that thiopurines may reduce risk of colorectal cancer in patients with ulcerative colitis and IBD-U, but evidence for a chemopreventative role from methotrexate, calcineurin inhibitors, anti-TNF and anti-integrin agents is lacking at present and they cannot be currently recommended solely for chemoprevention against colorectal cancer (GRADE: weak recommendation, low-quality evidence. Agreement: 93%).
  •  IBD patients receiving anti-TNF therapy should be counselled about the risks and benefits of continuing treatment throughout pregnancy. We suggest that, for patients with active disease or a high risk of relapse, it may be advisable to continue the drug throughout, while for those with inactive disease who wish to discontinue therapy it may be reasonable to stop at the start of the third trimester (GRADE: weak recommendation, very low-quality evidence. Agreement: 97.7%).
  • We suggest that BCG vaccination (if indicated) should be withheld until at least 6 months after birth, and rotavirus vaccine should not be given, for infants exposed in utero to biological therapies. Non-live vaccinations may be given according to standard vaccination schedules (GRADE: weak recommendation, very low-quality evidence. Agreement: 97.7%).
  • We suggest that genetic testing for monogenic disorders should be considered in adolescents and young adults who have had early onset (before 5 years of age) or particularly aggressive, refractory or unusual IBD presentations (GRADE: weak recommendation, very low-quality evidence. Agreement: 95%).
  • We recommend that IBD patients travelling abroad should receive pre-travel health advice, taking into account any immunosuppressive medication. Standard vaccination advice should be given, but those on immunosuppressive drugs should not receive live vaccination unless treatment has been discontinued for a minimum of 3 months (GRADE: strong recommendation, very low-quality evidence. Agreement: 95.7%).
  • We recommend that regular multidisciplinary team (MDT) meetings should be held to discuss IBD patients with complex needs (GRADE: strong recommendation, very low-quality evidence. Agreement: 97.9%).
  • We recommend that IBD patients and primary care physicians should be provided with a dedicated IBD telephone line or email service to allow timely advice and care, particularly during times of relapse or to discuss managing medications or treatment side effects. Services must have adequate administrative and funding models (GRADE: strong recommendation, low-quality evidence. Agreement: 100%).
  • We recommend that telephone or video virtual clinics can allow for the timely follow-up of stable IBD patients as an alternative to face-to-face clinic visits. These clinics need adequate administrative support and documentation, and methods to ensure contact with patients is maintained. Patients must have easy access to telephone or email advice and clinic access in the event of disease flare or patient concern about their IBD (GRADE: strong recommendation, low-quality evidence. Agreement: 95.7%).
  • We suggest that IBD patients who wish to participate in guided self-management should be provided with education sessions and written or electronic personalised information about their management, with ongoing support and access to the IBD service in the event of relapse (GRADE: weak recommendation, moderate-quality evidence. Agreement: 93.6%).
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Source: Journal Gut

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