Ulcerative colitis [UC] is a chronic inflammatory bowel disease [IBD] characterised by colonic inflammation extending to a variable extent from the rectum. Key updates to the European Crohn’s and Colitis Organisation (ECCO) Guidelines on the Medical and Surgical Treatment of Ulcerative Colitis in Adults have recently been published, which summarise the current evidence.
Key areas of importance for the medical treatment of UC include clinical response and remission for maintenance and induction therapies, as well as steroid-free clinical remission. However, a key area of debate is when to escalate treatment. There is less evidence in UC than in Crohn’s disease on the importance of early treatment escalation. At the same time, the experience of recurrent symptom flares can lead to physical and psychological harm, as can repeated exposure to corticosteroids, notes ECCO. “Although the cost of an intervention is a factor reflected in the GRADE [Grading of Recommendations Assessment, Development and Evaluation] process when forming the strength of recommendation, as international guidelines there will be local health economic considerations that this document cannot address. Nevertheless, it is clear that appropriate and timely selection of patients for higher-cost interventions is critical to achieve optimal health economic outcomes,” the new updated guidelines state.
A notable shift from the 2017 ECCO guidelines is the recommendation on considering treatment options based on patient disease severity. Previously, guidelines advised treatment according to the site of the disease and its activity, whereas revised guidelines recommend treatment under sections labelled ‘Medical management of mildly-to-moderately active UC’ and ‘Medical management of moderately-to-severely active UC’. The decision to change this particular section aims to ensure that patients with limited disease who are displaying active symptoms have access to appropriate treatment options.
Another notable change is in regard to new data and treatments. Following the recent MERIT-UC trial conducted by Herfarth et al, which took place in 2018 and concluded that methotrexate was not superior to a placebo in maintaining steroid-free response or remission in UC, it has been removed from the guidelines. New data for vedolizumab, ustekinumab, and tofacitinib have been included in the updated ECCO Therapeutic Guidelines on UC, which have been written in a way that allows for new updates to therapeutics to be included.
The following is a summary of the key recommendations in the 2022 ECCO Guidelines on the Medical Treatment of Ulcerative Colitis in Adults.
▶ Induction of remission in mildly-to-moderately UC
ECCO recommends 5-aminosalicylates at a dose of ≥2g/day [d] to induce remission in patients with mildly-to-moderately active UC [strong recommendation; quality of evidence low].
ECCO recommends topical [rectal] 5-ASA at a dose of ≥1g/d for the induction of remission in active distal colitis [strong recommendation, low-quality evidence].
ECCO suggests the use of oral 5-ASA [≥2g/d] combined with topical [rectal] 5-ASA over oral 5-ASA monotherapy for induction of remission in adult patients with active UC of at least rectosigmoid extent [weak recommendation; very low-quality evidence].
ECCO recommends using topical [rectal] steroids for the induction of remission in patients with active distal colitis [strong recommendation, very low-quality evidence].
ECCO suggests treatment with topical [rectal] 5-ASAs over topical [rectal] steroids for induction of remission in patients with active distal UC [weak recommendation, very low-quality evidence].
ECCO suggests the use of colonic-release corticosteroids for induction of remission in patients with active mild-to-moderate UC [weak recommendation, low quality of evidence].
ECCO suggests against the use of thiopurines as monotherapy for the induction of remission in patients with active UC [weak recommendation, very low quality of evidence].
ECCO recommends the use of oral 5-ASA at a dose ≥2g/d for maintenance of remission in UC patients [strong recommendation; very low quality of evidence].
ECCO suggests the use of topical [rectal] 5-ASA for the maintenance of remission in patients with distal UC [weak recommendation, very low-quality evidence].
ECCO recommends monotherapy with thiopurines for the maintenance of remission in patients with steroid-dependent UC or who are intolerant to 5-ASA [strong recommendation, moderate quality of evidence].
▶ Induction of remission in moderately-to-severely active UC
ECCO recommends oral prednisolone for induction of remission in non-hospitalised patients with moderately-to-severely active UC [strong recommendation; very low quality of evidence].
ECCO recommends treatment with anti-tumour necrosis factor [TNF] agents [infliximab, adalimumab, and golimumab] to induce remission in patients with moderate-to-severe UC who have inadequate response or intolerance to conventional therapy [strong recommendation, moderate-quality evidence].
ECCO recommends treatment with vedolizumab for the induction of remission in patients with moderately-to-severely active UC who have inadequate response or intolerance to conventional therapy [strong recommendation, low quality of evidence].
ECCO recommends treatment with tofacitinib to induce remission in patients with moderate-to-severe UC who have inadequate response or intolerance to conventional therapy [strong recommendation, moderate quality of evidence].
ECCO recommends treatment with ustekinumab for the induction of remission in patients with moderately-to-severely active UC with inadequate response or intolerance to conventional therapy. [strong recommendation, moderate quality of evidence].
▶ Maintenance of remission of moderately-to-severely active UC
ECCO recommends anti-TNF agents [infliximab, adalimumab, or golimumab] for the maintenance of remission in patients with UC who responded to induction therapy with the same drug [strong recommendation, high-quality evidence].
In UC patients who have lost response to an anti-TNF agent, there is currently insufficient evidence to recommend for or against the use of therapeutic drug monitoring to improve clinical outcomes.
ECCO recommends vedolizumab for maintenance of remission in patients with UC who responded to induction therapy with vedolizumab [strong recommendation, moderate-quality evidence].
We suggest the use of vedolizumab rather than adalimumab for the induction and maintenance of remission in patients with moderately-to-severely active ulcerative colitis [weak recommendation, low level of evidence].
ECCO recommends tofacitinib for maintaining remission in patients with UC who responded to induction therapy with tofacitinib [strong recommendation, moderate quality of evidence].
ECCO recommends ustekinumab for the maintenance of remission in patients with UC who responded to induction therapy with ustekinumab [strong recommendation, moderate quality of evidence].
While UC presents as a mild condition, it often leads to life-threatening and systemic complications that require urgent interventions. Up to 25 per cent of UC patients require a surgical intervention in their lifetime.
Key updates regarding surgery in cases of moderate-to-severe UC in the new ECCO guidelines include that reconstructive ileal pouch-anal anastomosis surgery can be offered to refractory and corticosteroid-dependent patients following evidence that this improves patient quality-of-life. The importance of pre-operative optimisation in patients with moderate-to-severe UC is also stressed. Another key update focuses on the use of steroids pre-operatively, which should be avoided or weaned off before restorative surgery, and where weaning is not possible, surgery should be postponed. Prophylactic anticoagulation therapy is also advised in adult patients with active UC to reduce the risk of venous thromboembolism, and systemic nutrition is advised despite a lack of evidence.
The updated guidelines state that the modified two-stage colectomy procedure may be associated with fewer complications, as patients are subjected to less surgery, but more evidence is needed to confirm this.
For patients with medically refractory UC, laparoscopic ileal pouch-anal anastomosis surgery is the advised choice. This technique is also an ideal option for young females, as it is associated with improved fecundity compared to open surgery. Ileo-rectal anastomosis (IRA) remains an option for patients with UC who have a minimally affected rectum.
Acute severe UC [ASUC] and medically-refractory UC represent the main indications for surgery in UC patients, the new ECCO guidelines note. ASUC may be the onset feature in up of one-third of UC patients, and is associated with a 30-to-40 per cent risk of colectomy after one or more severe exacerbations, and 10-to-20 per cent of patients with ASUC need a surgical intervention at their first admission.
Patients with ASUC require immediate hospitalisation, and the first-line treatment of ASUC consists of intravenous corticosteroid treatment. However, up to 30 per cent of patients fail to respond to conservative treatments and require a colectomy. In case of failure, after seven days without significant improvements, a surgical intervention is highly recommended to avoid the perioperative complications usually associated with emergent procedures, ECCO states.
Refractory UC includes steroid dependency and immunomodulator- or biologic-refractory disease, and is often accompanied by a deteriorated patient condition and is a recognised risk factor of poor postoperative outcomes; thus a staged procedure is often preferred, to improve patient status and minimise postoperative complications.
Despite the increasing availability of new pharmacological treatments, multiple attempts at conservative management and consequent therapeutic failures may affect the condition of patients with ASUC and refractory UC and considerably influence postoperative outcomes. Accordingly, multidisciplinary management of UC patients is of crucial importance to identify the best therapeutic pathway, says ECCO.
In recent decades, the surgical options for the treatment of refractory UC have evolved, combining technical advancements with a more comprehensive management of perioperative pathways.
▶ Medical management of ASUC
Intravenous corticosteroids as the initial standard treatment for adult patients with ASUC are recommended, as this treatment induces clinical remission and reduces mortality [EL3].
Either infliximab or cyclosporine should be used in adult patients with steroid-refractory ASUC. When choosing between these strategies, centre experience and a plan for maintenance therapy after cyclosporine should be considered [EL3].
There is currently insufficient evidence to determine the optimal regimen of infliximab rescue therapy in patients with ASUC refractory to corticosteroid therapy [EL4].
Third-line sequential rescue therapies with calcineurin inhibitors [cyclosporine or tacrolimus] in ASUC refractory to corticosteroid therapy may delay the need for colectomy, but are associated with high rates of adverse events and should only be administered in specialised centres [EL2a].
▶ Medical versus surgical management of refractory moderate-to-severe UC
Reconstructive surgery may be offered to refractory and corticosteroid-dependent patients and improves quality-of-life despite the risk of early and late complications [EL2b]. Proctocolectomy with end-ileostomy is an alternative for some patients and has lower morbidity and comparable quality-of-life [EL3a].
▶ Preoperative optimisation of refractory moderate-to-severe UC
Correction of altered body composition and nutrition imbalances is advised preoperatively, despite limited evidence [EL5]. There is no evidence to support routine enteral or parenteral nutrition to improve the surgical outcomes of patients with UC [EL5]. Iron supplementation is recommended when iron-deficiency anaemia is present [EL1].
Patients taking >20mg prednisolone for >six weeks are at increased risk of early complications and pouch-specific complications. Steroids should be weaned before restorative proctectomy or proctocolectomy, and if this is not possible, surgery should be postponed [EL4]. Preoperative thiopurines or cyclosporine do not increase the risk of postoperative complications [EL3]. Patients on biologics might be at increased risk of developing early and late pouch-specific complications; three-stage or two-stage modified approaches with deferred pouch construction could be considered under these circumstances [EL4]. Single-stage restorative proctocolectomy should be avoided in patients receiving biologics [EL5].
Prophylactic anticoagulation therapy in adult patients with active UC during hospitalisation is recommended, considering the high risk of venous thromboembolism [VTE] during UC flares [EL4].
▶ Surgical strategy of refractory moderate-to-severe UC
After total proctocolectomy for medically refractory UC, IPAA is the procedure of choice, but permanent end-ileostomy is also a reasonable option for some patients. A shared decision-making approach should be used to tailor procedure selection to the patient’s preference [EL3].
IPAA may be performed as a two or three stage procedure. Modified two-stage IPAA may be associated with fewer complications and shorter length of stay than three-stage or two-stage IPAA in patients with medically refractory UC operated in expert centres, but more evidence is needed [EL3].
▶ Technical aspects of surgical approaches for refractory moderate-to-severe UC
IPAA may be constructed using either a stapled or a handsewn technique, with comparable functional outcomes. Thus, the type of anastomosis should be left to the surgeon’s discretion [EL2].
Laparoscopic surgery is the preferred approach to patients with medically refractory UC, as it is associated with lower intra- and postoperative morbidity, faster recovery, fewer adhesions and incisional hernias, shorter hospital length of stay, improved female fecundity, and better cosmesis [EL2].
Although associated with an increased risk of rectal dysplasia, cancer, and dysplasia or cancer recurrence, patients with UC and a minimally affected rectum can be offered the option of an ileo-rectal anastomosis [IRA] [EL4].
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