Treatment of Inflammatory Bowel Disease and Pediatric Onset Multiple Sclerosis With Ocrelizumab and Ustekinumab in a JC-virus Positive Adolescent

**Background:** Inflammatory bowel disease (IBD) and multiple sclerosis (MS) are known to be associated, and their comanagement is complicated by the fact that many disease-modifying therapies (DMTs) for one condition may exacerbate the other. For example, interferon beta and glatiramer acetate may worsen IBD, while tumor necrosis factor inhibitors used for IBD can exacerbate MS. Natalizumab carries risk of progressive multifocal leukoencephalopathy (PML) in JC-virus positive patients. Fingolimod is the only FDA-approved DMT for pediatric-onset MS (POMS), and no established guidelines exist for managing concurrent POMS and IBD. Successful comanagement with ocrelizumab and ustekinumab had not been previously reported.

**Methods:** This is a single case report of a 17-year-old G1P1 female who presented four months postpartum with right leg weakness, paresthesia, and blurry vision. MRI of the brain, cervical spine, and thoracic spine showed periventricular opacities and multiple lesions in the brain and cerebellum, leading to a diagnosis of POMS. Lumbar puncture showed albuminocytologic dissociation. She was treated with high-dose IV corticosteroids with resolution of symptoms. Six weeks later, she was diagnosed with Crohn's disease based on upper endoscopy and colonoscopy findings including scalloping in the duodenum, patchy aphthous ulceration of the ascending colon, and ulceration/erythema of the terminal ileum with biopsies showing diffuse chronic active inflammation, cryptitis, crypt abscesses, and plasma cell/lymphocytic infiltration. Laboratory evaluation showed hemoglobin 10.7 g/dL and elevated C-reactive protein (6 mg/dL, ref range 0–1 mg/dL). JC-virus testing was positive with index <0.9.

**Key Results:** Natalizumab was initiated 4 months after POMS diagnosis following an 8-week insurance delay. While MS remained stable (follow-up MRI showed three new T2 hyperintense lesions without T1 gadolinium enhancement, thought to have developed before starting DMT, and no clinical relapse), Crohn's disease remained poorly controlled with continued weight loss, loose watery stools, and abdominal pain despite multiple steroid courses (total 1670 mg prednisone and 810 mg budesonide while on natalizumab). After 10 months of natalizumab, repeat endoscopy showed no improvement. Natalizumab was discontinued 14 months after initiation, and the patient was started on ocrelizumab and ustekinumab. Crohn's disease symptoms dramatically improved with ustekinumab, including weight gain, resolution of abdominal pain, and normalization of inflammatory markers. After 18 months on combination therapy, the patient's Crohn's disease remains in clinical remission without need for further corticosteroids, with no clinical or laboratory side effects. The most recent MRI brain at 18 months showed only stable MS plaques, and the patient remains neurologically asymptomatic.

**Clinical Implications:** This case demonstrates that combination therapy with ocrelizumab and ustekinumab can be an effective strategy for managing concurrent POMS and IBD when monotherapy with natalizumab is insufficient or not a viable long-term option due to JC-virus positivity. Ocrelizumab successfully controlled MS without exacerbating IBD, while ustekinumab induced and maintained Crohn's disease remission without worsening MS. Notably, ustekinumab was studied in Phase II RCTs for MS in adults and did not show efficacy for MS but was well tolerated. In the absence of established treatment guidelines, the authors recommend considering this combination when standard treatment modalities are not viable options.