Microscopic Colitis: Is Vedolizumab An Option?

Microscopic colitis (MC) is a condition that is typically found in patients over 60 years old who present with chronic, watery, nonbloody diarrhea.¹ MC is relatively common, with a prevalence between 48 to 219 per 100,000 persons.² There are 2 subtypes, collagenous colitis (CC) and lymphocytic colitis (LC), which can be distinguished based on pathological evaluation. Many patients being evaluated for chronic diarrhea will undergo a colonoscopy, in which the initial endoscopic findings are typically normal in MC. The distribution of MC within the colon is relatively patchy. Therefore, random biopsies are typically recommended throughout the entire colon, especially as MC has been found in approximately 7.5% of patients undergoing evaluation for chronic diarrhea.¹ Within these random biopsies are pathognomonic changes associated with MC. LC is defined by >20 intraepithelial lymphocytes per 100 surface epithelial cells, while CC consists of a subepithelial collagen band that is >7 to 10 µm.³

The 2016 American Gastroenterological Association guidelines review detailed several treatment options for MC, including budesonide, mesalamine, cholestyramine, bismuth salicylate, probiotics, and prednisone.¹ The goal of treatment is to induce remission of the patient’s symptoms as well as minimize medication side effects and improve quality of life.¹ Although it does not appear that MC leads to any increased risk for mortality, it can still have a profound impact on a patient’s quality of life and overall well-being.¹

Unfortunately, even if remission can be achieved, up to 80% of patients can experience a relapse in symptoms.⁴  In these situations, it is important to consider alternate causes of chronic diarrhea including medications, irritable bowel syndrome, celiac disease, and infectious etiologies. Some patients may require prolonged, tapered dosing of budesonide over 6 to 12 months, which can be challenging in real-world settings  due to medication costs and compliance.¹ When prescribing budesonide, it is also important to note the specific formulation, as 3 mg capsules are available but are formulated to release in the terminal ileum and proximal colon, while 9 mg tablets release throughout the entire colon.⁵ Therefore, the 3 mg capsules may allow for easier tapering schedules but may not necessarily deliver budesonide to the more distal colon. 

Based on the relatively high relapse rate and desire to limit prolonged use of budesonide (albeit, not a systemic steroid), there is a significant clinical need for additional treatment options. Vedolizumab (VDZ) is a monoclonal antibody against the α4β7 integrin found on T-cells that inhibits the migration of T-cells into the gastrointestinal tract.⁶ VDZ use inhibits the binding of T-cells to mucosal addressin cell adhesion molecule-1.⁶ VDZ is currently Federal Drug Administration (FDA) approved for use in ulcerative colitis and Crohn disease and is administered intravenously. There is an induction dosing of 300 mg given at 0, 2, and 6 weeks followed by maintenance dosing of 300 mg every 8 weeks. Based on its unique mechanism of action and safety profile, there is increasing interest in using VDZ in patients with refractory MC, though there is a current paucity of clinical data in the literature. 

Riviere et al published an international case series that included 11 patients with refractory MC from Europe and Canada.⁷ Clinical remission was found in 5/11 patients after the 3 initial loading doses. Median time to remission was 1 month. Histological remission (with biopsies taken during flexible sigmoidoscopy) was seen in 3/4 patients with clinical remission and in 0/5 patients without clinical improvement.⁷

Two additional studies not included in the case series published by Riviere et al have recently been conducted.  A group led by Shipley et al published their experience with VDZ in 9 patients with refractory MC at a single center.⁸ All patients achieved clinical response with induction therapy. However, 3 patients did not maintain response. Most patients achieved clinical response within 3 weeks of starting VDZ. 

A similar small case series was reported by Jennings et al that included 3 patients with MC.⁹ All 3 patients had complete resolution of their symptoms after the first 2 doses and also required maintenance dosing every 6 to 8 weeks. 

Although the developing data supporting the use of VDZ in MC does appear at least somewhat promising, there are many potential barriers to its use in real world settings. MC is considered an off-label indication for VDZ. Thus, there may be difficulties obtaining authorization from insurance companies. Additionally, some patients may not be interested in receiving intravenous infusions, whether at an infusion center or at home, though the infusion typically only lasts 30 minutes.⁶ There is now a subcutaneous version of VDZ available outside the United States (US) which may be available in the US in the future, pending FDA review. Although it is relatively well tolerated, patients still have to be monitored and counselled about possible hypersensitivity reactions, infection risks, elevated serum transaminases, and progressive multifocal leukoencephalopathy.⁶

References

1. Nguyen GC, Smalley WE, Vege SS, Carrasco-Labra; Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the medical management of microscopic colitis. Gastroenterol. 2016;150(1):242-246. doi:10.1053/j.gastro.2015.11.008
2. Pardi DS, Tremaine WJ, Carrasco-Labra A. American Gastroenterological Association Institute technical review on the medical management of microscopic colitis. Gastroenterol. 2016;150(1):247-274. doi:10.1053/j.gastro.2015.11.006
3. Tome J, Kamboj AK, Pardi DS. Microscopic colitis: a concise review for clinicians. Mayo Clin Proc.  2021;96(5):1302-1308. doi:10.1016/j.mayocp.2021.03.022
4. Miehlke S, Madisch A, Voss C, et al. Long-term follow up of collagenous colitis after indication of clinical remission with budesonide. Aliment Pharmacol Ther. 2005;22(11-12):1115-9. doi: 10.1111/j.1365-2036.2005.02688.x
5. Iborra M, Alvarez-Sotomayor D, Nos P. Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis. Clin Exp Gastroenterol. 2014;7:39-46. doi: 10.2147/CEG.S34715
6. Entyvio® (vedolizumab) [package insert]. Deerfield, IL; Takeda; Revised March 2020.
7. Riviere P, Munch A, Michetti P, et al. Vedolizumab in refractory microscopic colitis: an international case series. J Crohns Colitis. 2019;13(3):337-340. doi:10.1093/ecco-jcc/jjy169
8. Shipley LC, Ravi S, Russ KB, Weber FH. Vedolizumab therapy in refractory microscopic colitis: a single center case series. Clin Gastroenterol Hepatol. Published online February 26, 2021. doi: 10.1016/j.cgh.2021.02.037
9. Jennings JJ, Charabaty A. Vedolizumab-induced remission in 3 patients with refractory microscopic colitis: a tertiary care center case series. Inflamm Bowel Dis. 2019;25(8):e97. doi:10.1093/ibd/izz042