Department of Research & Evaluation News

For years, people living with relapsing forms of multiple sclerosis (MS) have depended on powerful medications to keep their disease under control. One of the most effective treatments has been rituximab, a therapy that works by depleting B cells, which are the immune cells that drive inflammation with MS.

However, new research from Kaiser Permanente Southern California is challenging long‑held assumptions about how often patients need to take these medications to stay well.

“Our research shows that extending rituximab dosing to every 12 months after a year of stability is just as effective as the traditional every-6-months schedule, even when B-cell counts are high,” said the study’s lead author Annette Langer-Gould, MD, PhD, an affiliated investigator with the Kaiser Permanente Southern California Department of Research & Evaluation, and a neurologist at the Kaiser Permanente Los Angeles Medical Center. “This approach doesn’t increase the risk of disease activity and allows us to tailor treatment to each patient’s needs.”

Study cohort included more than 600 people

For this study, researchers analyzed data from over 600 patients with MS within Kaiser Permanente Southern California to simulate a randomized controlled trial, known as a target trial.

Their goal was to assess whether extending rituximab 500mg dosing intervals to 12-month intervals increased the risk of MS disease activity returning after one year of stability on the standard 500mg taken every 6 months. They compared this approach to maintaining the traditional 6-month regimen.

The findings were published in the January 27, 2026 issue of Neurology.

The study is a continuation of Dr. Langer-Gould’s work investigating rituximab, which is less expensive than traditional MS medications, as a treatment for MS.

“Rituximab is a highly effective therapy for people with relapsing forms of MS, and it has been a game changer for the field and for people with this disease,” she said.

Early, effective treatment is essential for preventing long‑term disability in MS. Yet treatment comes with tradeoffs. Rituximab and similar B‑cell–depleting therapies can suppress the immune system for long periods, which increases the risk of infections and lowers protective antibody levels. “If you give too much of this and patients become B‑cell depleted for years, the risk of infection goes up,” Dr. Langer-Gould said.

Because many MS patients are young and otherwise healthy, physicians must balance the need to control MS disease activity with the risk of overtreatment. These concerns are what motivated Dr. Langer‑Gould and her colleagues to investigate whether patients really need continuous, intensive B‑cell suppression to remain stable.

The findings are striking

While the general theory behind their findings was consistent with several other preliminary assessments conducted outside of the U.S., this study moved the research forward by showing that not just lowering but also extending dosing after only 1 year of stability works just as well as staying on high doses taken every 6 months, regardless of other patient characteristics. This study showed that “you do not need continuous B‑cell depletion to prevent MS relapse,” Dr. Langer-Gould said.

In this extended‑interval dosing study, “97–98% of the patients had no disease activity whatsoever with up to 4 years of follow‑up, and most of them had significant return in their B cells,” she added

This means that even when B cells come back between infusions, most people remain clinically stable, which challenges the assumption that patients must stay continuously depleted to prevent relapses.

Study raises new possibilities

These findings open the door to a future with fewer clinic visits, fewer infusion‑related risks, and possibly lower costs for patients and health care organizations. They also raise an important question: Could some people take low doses only every 2 years or eventually stop treatment altogether?

Dr. Langer‑Gould believes this possibility deserves investigation. Many Kaiser Permanente Southern California patients are on every 2-year dosing, and some have stopped rituximab for practical or medical reasons, such as insurance changes, pregnancy, cancer treatment, or low immunoglobulin levels. What’s surprising, she said, is how few experienced a return of their MS flare-ups: “We very rarely see any of them come back with disease activity,” she said.

These observations have inspired her team to consider future research to identify who might be able to safely receive infusions only once every 2 years or discontinue treatment long term. If proven safe, this would mark a major shift in MS care: A move toward personalized, minimalist treatment strategies that still protect patients from relapses but spare them unnecessary medication exposure.

Dr. Langer‑Gould’s work reinforces a powerful idea: More medication isn’t always better. By tailoring treatment to what patients need, clinicians may help people with MS stay healthier, avoid complications, and live their lives with greater freedom, she said.

In addition to Dr. Langer-Gould, other authors on the study include Bonnie H. Li, MS; Jessica B. Smith, MPH; A. Scott Nielsen, MD; Brandon E. Beaber, MD; Sonu M. Brara, MD;  Samira Amirova, NP; Fernando Torres, MD; and senior author, Stanley Xu, PHD; all of Kaiser Permanente Southern California.