https://orcid.org/0000-0002-1032-1284
To the Editors,
Ocrelizumab, an anti-CD 20 humanized monoclonal antibody approved in 2017 for treating multiple sclerosis, has been associated with ensuing colitis in some case reports.1–4 We report the first case of ocrelizumab-induced severe microscopic colitis after 1 dose, requiring hospitalization for supportive management.
A 60-year-old female with primary progressive multiple sclerosis was given ocrelizumab 600 mg/IV and 2 months later developed prolonged non-bloody diarrhea, resulting in severe hypokalemia. There was no personal or family history of inflammatory bowel disease. Stool was negative for infection and TTG, serum IgA, TSH, Hgb, and CRP levels were normal.
Colonoscopy was normal to the terminal ileum. On histology, the ileum had intact villous architecture with mild intraepithelial lymphocytosis. The colon had increased intraepithelial lymphocytes in the surface epithelium, lamina propria, and crypts. There were plasma cells and mild active inflammation but no alteration of crypt architecture or granuloma. Clinical and histological findings supported a diagnosis of lymphocytic colitis (Figure 1).
This H&E-stained photomicrograph of large bowel mucosa shows normal crypt architecture alongside increased chronic inflammatory cells within the lamina propria and numerous intraepithelial lymphocytes, consistent with an interpretation of lymphocytic colitis.
The patient was given oral budesonide tapered over 12 weeks and symptoms resolved. Ocrelizumab was discontinued and a rechallenge was planned with prophylactic budesonide at least 2 weeks prior to the next infusion. One month prior to the planned rechallenge, the patient’s diarrhea and hypokalemia recurred. Repeat work-up showed no infection and normal mucosa on colonoscopy. Biopsies remained consistent with lymphocytic colitis. She was re-treated with budesonide and after 2 weeks, given a second cycle of ocrelizumab in 2 half-doses (300 mg/IV) 1 week apart. No further diarrhea ensued.
Ocrelizumab-induced colitis was first reported in 2020 and a 2023 study showed 38 attributable cases from the FDA Adverse Event Reporting System.1,4–6 It is hypothesized that dysregulation of immune equilibrium occurs in colonic tissue due to depletion of B-cells, reducing anti-inflammatory cytokines.7 Symptoms occurred any time after the last infusion from a median between 8 and 60 months and included abdominal pain, non-bloody, bloody diarrhea, and fever.4 It can be mild to severe, resulting in colectomy in the most extreme cases.2,3 Some cases describe development of, worsening, or unmasking of inflammatory bowel disease, but no reports of microscopic colitis exist.3,4
Endoscopic and histologic features include erythema, ulcerations, spontaneous bleeding, intraepithelial lymphocytosis, deep ulcerations, neutrophilic infiltration, crypt abscesses, and active chronic colitis.3,8 Therapeutic interventions range from mesalamine, glucocorticoids, biologics, and surgery.4 There are no reports of microscopic colitis and our case was particularly severe resulting in hospitalization twice with profound diarrhea and hypokalemia. It is important for prescribers to be aware of this rare but potentially serious off-target effect.
Funding
None declared.
Conflicts of Interest
V.J. has received consulting/advisory board fees from AbbVie, Alimentiv, Anaptyis Bio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ensho, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, MRM Health, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Spyre, Synedgen, Takeda, Teva, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Eli Lilly, Fresenius Kabi, Janssen, Pfizer, Shire, Takeda, Tillotts. M.C. and C.Z. declared nothing to disclose.
