Long-term outcome of ulcerative proctitis

Ulcerative colitis is an idiopathic and chronic inflammatory disorder of the colorectal mucosa. Disease extent may vary, with approximately 30% of patients having inflammation involving the rectum only, termed ‘ulcerative proctitis’ (UP). Patients with UP manifest with rectal bleeding, urgency and tenesmus. Endoscopy typically shows diffuse inflammation of the rectum only.¹,² Treatment of UP is mainly composed of topical and oral compounds of 5-aminosalicylic acid (5-ASA) and corticosteroids. In general, locally administered 5-ASA preparations have been shown to be more effective than oral compounds. The combination of topical and oral 5-ASA as well as topical/oral steroids should be considered for therapy escalation.³,⁴ Patients refractory to the latter should be re-evaluated to exclude compliance failure, infections or proximal disease extent. Previous studies have demonstrated that proximal extension takes place in 28% of UP patients during 5 years of follow-up.² A considerable knowledge gap currently exists as to the optimal therapy in cases of UP resistant to 5-ASA and corticosteroids. Immunomodulators (such as azathioprine, 6-mercaptopurine and cyclosporine) and/or monoclonal antibodies to tumour necrosis factor alpha (TNF-α) (such as infliximab, adalimumab and golimumab), anti-integrins (vedolizumab)⁵ or even topical tacrolimus⁶ may be considered in resistant cases.

In the study by Dubois et al.,⁷ 118 UP patients were included and followed for up to 20 years. Thirty-six (31%) were refractory to conventional therapy with 5-ASA and steroids. Topical 5-ASA was prescribed in 115 patients (97%) and topical steroids in 66 (56%). The most common combination therapy was topical 5-ASA combined with topical steroids. A course of oral steroids was necessary in 48 patients (41%). Eventually, 22 patients (19%) were prescribed azathioprine for refractory UP. Azathioprine was successful as a monotherapy in only 11% of patients (2/19), while 33 patients (28%) required further treatment escalation to biological agents, including 25 (76%) to anti-TNFs and eight (24%) vedolizumab. Fourteen patients (42%) achieved remission with their first biological agent and 13 patients (40%) were switched to a second biological agent, with subsequent response obtained in 38% of them. Third-line biological agents were administered in five patients and were successful in four (80%) patients. In total, 70% of those who received biological therapy achieved clinical remission. In terms of treatment safety, eight of 19 (42%) patients developed adverse events under azathioprine therapy, requiring discontinuation in seven of them; 12/33 (36%) patients on biological therapy reported adverse events leading to therapy cessation.

We believe this study addresses a cardinal clinical question, not studied enough previously. It shows that 30% of UP patients who become resistant to conventional therapies can benefit from immunomodulators and biological agents. The authors conclude that those receiving biological agents may do better clinically and endoscopically and also demonstrate fewer adverse events than UP patients treated with immunomodulators. This goes in line with previous studies, which demonstrate favourable outcomes of refractory UP patients with anti-TNF-α or vedolizumab.⁸ Ustekinumab and tofacitinib therapy has not been described in these patients. Nevertheless, it should be noted that although in the current study clinical remission with biological therapy was reached in 70% of the patients, only 42% achieved clinical remission with their first biological therapy. Furthermore, the authors addressed disease extension beyond proctitis as treatment failure. Comparing such patients to the ‘classic’ UP group of 118 patients and to left-sided colitis controls could be interesting. A previous study has shown that the number of previous disease flares has been significantly associated with extension of inflammation in UP patients.⁵ In this regard, assessment of prognostic factors predicting refractory UP or disease progression could also be of clinical value. Moreover, as the authors rightfully mention, the database includes patients with over 20 years of follow-up, and therefore biological therapies and especially novel formulations such as anti-integrins, available only in later years, could have been under-used. In addition, endoscopic data were available for only 66/118 patients and only before therapy escalation in refractory UP patients.

To conclude, the study by Dubois and colleagues⁷ highlights an unmet need within the scope of inflammatory bowel disease (IBD) clinical therapy. Although ample data exist as to therapies for moderate/severe ulcerative colitis patients, only few studies have addressed the outcome and prognosis of refractory and extending UP. The current study demonstrates that thiopurines, anti-TNFs and vedolizumab are all valid therapeutic options in such patients. Future studies ought to explore the efficacy and safety of other newer biological agents and small molecule therapies for refractory UP.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Uri Kopylov https://orcid.org/0000-0002-7156-0588