Study ties MS therapy to higher risk of inflammatory bowel disease
Rituximab seen posing higher risk than others, yet figure remains low
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A study linked a common MS treatment to a heightened risk of inflammatory bowel disease. (Photo by iStock)
Treatment with rituximab, an anti-CD20 therapy that is used off label for multiple sclerosis (MS), may be associated with a significantly higher risk of developing inflammatory bowel disease (IBD), particularly Crohn’s disease, a large study in Sweden found.
After accounting for patient differences, researchers found the risk was about 10 times higher with rituximab than with three other disease-modifying therapies (DMTs) approved for MS. However, the overall risk remained low, with fewer than 2% of patients developing IBD within 10 years of starting treatment.
“This is the first large study to quantify the risk of inflammatory bowel disease associated with anti-CD20 treatment for MS,” Peter Alping, MD, PhD, a postdoctoral researcher at Karolinska Institutet in Sweden and the study’s lead author, said in a university news release. “The results show that this is a potential adverse effect that should be considered when choosing an MS treatment.”
Yet this risk “needs to be weighed against the benefits for the individual patient,” Alping said. “Anti-CD20 drugs are among the most effective treatments for preventing MS relapses.”
The study, “Risk of Inflammatory Bowel Disease After Anti-CD20 Treatment in Multiple Sclerosis,” was published in JAMA Neurology.
Off-label use
Rituximab (marketed as Rituxan and others) is an antibody-based therapy that targets the CD20 protein found on the surface of B-cells, immune cells involved in MS. By reducing the number of these cells, rituximab helps control the inflammation that damages nerve cells and contributes to MS symptoms.
Although rituximab was the first anti-CD20 therapy investigated for MS, it was never approved for the disease. It is nevertheless widely used off label and is now the most commonly prescribed DMT in Sweden. Newer anti-CD20 therapies have since gained approval, including Ocrevus (ocrelizumab), Kesimpta (ofatumumab), and Briumvi (ublituximab).
In recent years, reports of IBD cases in people with MS have raised concerns that anti-CD20 therapies may increase the risk of developing the condition. IBD causes ongoing inflammation in the digestive tract and includes Crohn’s disease, which can lead to symptoms such as abdominal pain, persistent diarrhea, and sometimes bloody stools.
However, “data from larger observational studies on anti-CD20–associated IBD in MS are lacking,” the researchers wrote.
The team analyzed Swedish health records covering 9,251 adults with relapsing-remitting MS, ages 18 to 55, who started treatment between January 2011 and December 2023.
The analysis covered 13,748 periods of treatment: 6,481 with rituximab and 7,267 with three other DMTs approved for MS — Tysabri (natalizumab), Tecfidera (dimethyl fumarate), and Gilenya (fingolimod). Some patients contributed more than one treatment period.
For comparison, the team also examined records from 40,925 people in the general population who did not have MS. None of those included in the study had evidence of previous IBD.
During follow-up, 40 new cases of IBD were recorded during rituximab treatment, compared with four during treatment with the other three MS therapies. Another 120 cases were recorded in the general population. Crohn’s disease accounted for most IBD cases associated with rituximab (62%).
When researchers accounted for the duration of follow-up, they estimated approximately 110 new IBD cases per 100,000 people treated with rituximab for one year, compared with 13 among those receiving other MS therapies and 41 in the general population.
After adjusting for factors such as age, sex, MS duration, previous treatments, and disease severity, the risk of developing IBD was about 10 times higher with rituximab than with the other three MS therapies. This finding held up when researchers repeated their analyses using different methods, including stricter criteria for identifying IBD.
Despite the higher risk, IBD remained uncommon, with fewer than 2% of people in any treatment group developing the condition within 10 years after starting treatment. To help put things in perspective, the researchers estimated that, for every 131 people treated with rituximab for five years instead of one of the other three MS therapies, one additional case of IBD would occur.
“Clinicians and individuals with MS should be aware of the risk of IBD and remain vigilant for gastrointestinal symptoms during treatment with anti-CD20 therapy,” the researchers wrote. “Careful consideration should also be given before initiating treatment with anti-CD20 therapy in those with MS and a history of IBD.”
They called for more research “to explore whether treatment modifications or monitoring strategies could mitigate IBD risk with anti-CD20 therapy and to establish clinical risk factors for anti-CD20–associated IBD.”
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