From the Guidelines
The management of refractory ulcerative proctitis involves a step-wise approach, starting with optimization of current therapy, followed by escalation to systemic corticosteroids, immunomodulators, and biologic agents, with surgery being considered for truly refractory cases. When patients fail to respond to topical mesalamine or corticosteroids, the first step is to review current symptoms, treatment history, and adherence to medical therapy, as poor adherence or inadequate drug delivery can be a cause of refractory disease 1.
Optimization of Current Therapy
The initial step is to ensure that conventional therapy has been used appropriately, with attention to the formulation of topical therapy and whether it was used in conjunction with an adequate dose of oral therapy 1. An abdominal X-ray can be useful to diagnose proximal constipation, and if there is visible faecal loading, a laxative should be considered 1.
Escalation of Therapy
If disease persists, systemic corticosteroids such as prednisone 40-60mg daily with a gradual taper over 8-12 weeks may be necessary. For steroid-dependent or steroid-refractory cases, immunomodulators like azathioprine (2-2.5mg/kg/day) or 6-mercaptopurine (1-1.5mg/kg/day) should be considered. Biologic agents represent the next step, with anti-TNF medications, vedolizumab, or JAK inhibitors like tofacitinib being effective options 1.
Surgical Intervention
For truly refractory cases not responding to medical therapy, surgical intervention with proctocolectomy with ileal pouch-anal anastomosis may be required. The escalation approach is based on the understanding that localized inflammation in proctitis can become more extensive and severe if inadequately treated, and that targeting different inflammatory pathways may overcome treatment resistance 1.
Some key points to consider in the management of refractory ulcerative proctitis include:
- Reviewing current symptoms, treatment history, and adherence to medical therapy
- Optimizing conventional therapy, including topical and oral medications
- Escalating therapy to systemic corticosteroids, immunomodulators, and biologic agents as needed
- Considering surgical intervention for truly refractory cases
- Targeting different inflammatory pathways to overcome treatment resistance 1.
From the Research
Management of Refractory Ulcerative Proctitis
The management of refractory ulcerative proctitis can be challenging due to the limited evidence regarding drug efficacy in this clinical situation 2.
- Medical management may involve the use of azathioprine, topical tacrolimus, and anti-TNF monoclonal antibodies as rescue treatment for refractory ulcerative proctitis 2.
- Other biologics may be of benefit despite a lack of dedicated clinical trials 2.
- Experimental therapies such as epidermal growth factor enemas, appendectomy, or fecal transplantation may be tried before restorative proctocolectomy with J pouch anastomosis, which has demonstrated good results with regards to clinical remission and quality of life 2.
Treatment Options
- Topical 5-aminosalicylic acid (5-ASA) suppository has been shown to be effective for induction of clinical response or remission and prevention of relapse in several studies 3.
- Combined topical steroids and 5-ASA may be more effective than topical 5-ASA or topical steroids alone to induce response 3.
- Azathioprine may be effective in patients with ulcerative proctitis, according to one observational study 3.
- Mesalazine suppository has been the first-line therapy for patients with ulcerative proctitis due to its high effectiveness and safety 4.
Approach to Treatment
- The short-term goal of treatment in ulcerative proctitis is to induce remission, while long-term goals are to maintain remission and prevent disease progression 5.
- Topically administered 5-ASA and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice 5.
- Refractory patients should be re-evaluated to exclude compliance failures, infections, or proximal disease extent, and may require immunomodulators or biological therapy 5.
- Identifying early prognostic factors that herald a disabling disease progression will help in optimizing treatment and avoiding surgery 6.