Kesimpta: A Lesson in Side Effects

Did you ever play the board game Clue when you were a kid?

“The murderer was Professor Plum in the Kitchen with the Candlestick”.

After seven months of medical detective work stemming from my near-fatal gastrointestinal hemorrhage on January 27, 2026, I finally have answers:

“The attempted murderer was Kesimpta in the Cecum with the Drug-induced Colitis”.

All joking aside, I cannot begin to tell you how relieved I was to hear from my gastroenterologist that the inflammation previously observed in my cecum (where the small and large intestine meet) had resolved, and my colonoscopy on August 18, 2026, was normal. My gastroenterologist has concluded that the inflammation and features suggestive of Inflammatory Bowel Disease (IBD) observed on my previous colonoscopy and capsule endoscopy were the result of drug-induced immune-mediated colitis. Had Crohn’s Disease (our other prime suspect) been our culprit, it would not have fully healed on its own without medication and/or diet changes. The fact that my cecum has recovered after a few months off Kesimpta is conclusive inculpatory evidence of Kesimpta’s role in producing an IBD-like condition in my cecum, and likely also my near-fatal hemorrhage. While the exact location of the hemorrhage was never isolated, my gastroenterologist has opined that inflammation likely eroded into a major blood vessel, producing the shock-level bleeding.

Way back when I first started taking Kesimpta, I wrote a blog post titled “Cue the Side Effects”. In it, I reflected on my early side effects and concluded: “All drugs have side effects, but MS drugs really do take the cake.” When I wrote those words, I truly didn’t know the half of it. Drug-induced immune-mediated colitis wasn’t even on my radar. I knew that death was a potential side effect, because Kesimpta comes with a warning about the possibility of developing Progressive Multifocal Leukoencephalopathy (PML), a rare and often fatal brain disease caused by infection by, or re-activation of the John Cunningham virus. However, I quieted my concern about this by reminding myself that Kesimpta has never actually been associated with a single case of PML. Arzerra, the higher dosage of Ofatumumab used to treat certain cancers, has been associated with cases of PML, and this contributes to the need for this side effect warning for Kesimpta. I was blissfully unaware that Disease Modifying Therapies (DMTs) that deplete CD20+ B cells, like Rituxin (rituximab), Ocrevus (ocrelizumab), Kesimpta (ofatumumab), and Briumvi (ublituximab-xiiy) carry a rare but known side effect of producing drug-induced immune-mediated colitis. That is, I was blissfully unaware of this until it nearly killed me.

Now, I don’t write about this to alarm anyone currently taking Kesimpta, Rituxin, Ocrevus, or Briumvi. This truly is a rare side effect and the vast majority of people taking these DMTs will never experience it. I got unlucky. Kesimpta didn’t agree with me. Back when I was choosing my first DMT I wrote a blog post titled “It’s a Multiple Choice Exam, and Wrong Answers will be Penalized”. At that time I picked “Option D: Kesimpta”. It took 4.5 years for that penalty to come along, but oh boy did I ever get penalized for that wrong answer! But my wrong answer might be the DMT that gives someone else a decade or more of quiet disease activity and few, if any, side effects.

I would like to see a side effect warning added to Kesimpta and all of the DMTs that deplete CD20+ B cells for drug-induced immune-mediated colitis. Had I not had the good fortune to have a gastroenterologist who had made a connection between Kesimpta and drug-induced immune-mediated colitis in his own practice, I may well have been erroneously diagnosed with Crohn’s Disease. Thankfully, my gastroenterologist was suspicious of Kesimpta’s role and investigated my inflammation and ulceration suggestive of IBD accordingly. To that end, I have reported my side effects to the Kesimpta Go Program (Novartis’ patient-support program) and to Health Canada. There are a not insignificant number of reports of drug-induced immune-mediated colitis associated with DMTs that deplete CD20+ B cells in the scientific journals. This report details the experience of a 43-year-old woman with MS who developed drug-induced immune-mediated colitis following treatment with Ocrevus leading to total colectomy. This report details the experience of a 56-year-old woman with MS who developed severe drug-induced immune-mediated colitis 3 months after initiating Kesimpta, requiring hospitalization and treatment discontinuation. In a population-based retrospective cohort study from Iceland, 651 patients treated with Rituxin (for all indications) were studied and 7 developed IBD, a higher incidence than expected compared to the general population. This study is a comprehensive narrative review of contemporary drug causes of inflammatory colitis and it specifically addresses the mechanism of colitis, prevalence, and clinical presentation of drug-induced immune-mediated colitis in patients taking Rituxin and Ocrevus. These papers indicate that there is a potential class effect of anti-CD20 DMTs in relation to drug-induced immunte-mediated colitis in MS patients. They conclude that clinicians should monitor for gastrointestinal symptoms in MS patients receiving any anti-CD20 DMT. For me, perhaps the first and only warning sign before my catastrophic hemorrhage was that I had developed issues with constipation shortly after starting Kesimpta. I managed this side effect, but it was troublesome throughout my entire 4.5 years on the drug. It was always passed off as likely attributable to MS itself and not the drug. However, now that I’ve been off Kesimpta for several months this has resolved, leading me to conclude that it always was a drug side effect.

After months of wondering whether I had developed a second autoimmune disease and a third chronic illness, I feel like an enormous weight has been lifted from my shoulders. Learning that I had developed drug-induced colitis and that it had healed was truly the best news that I could have asked for in the circumstances. I finally feel like I can close the chapter on my near fatal hemorrhage. I have an explanation (even if a somewhat imperfect one where the exact source of the bleeding was never isolated) and I have some assurance that this isn’t likely to be a repeat event now that I’ve pinpointed the perpetrator and removed it.