What are the long-term effects of B-cell therapy in MS?

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When you have multiple sclerosis (MS), your immune system works against you. Uncontrolled, immune cells attack the protective layer that surrounds your nerve fibers. Doctors used to think your immune T cells were the main culprit. Immune B cells that produce antibodies were viewed as innocent bystanders.

That changed when scientists began to realize that existing MS treatments worked in part by changing what B cells were doing. Would it be possible to treat MS by attacking B cells directly?

Doctors already had a way to do this: an antibody-based treatment called rituximab, which is used to fight a type of cancer called B-cell lymphoma. A 2008 study showed that rituximab helped people with MS. After 48 weeks, the study participants had fewer brain lesions and also avoided recurrences.

The FDA approved a rituximab-like drug called ocrelizumab (Ocrevus) for MS in 2017. You get it through an IV every 6 months. In 2020, the FDA approved another drug called Ofatumumab (Kesimpta) that works in the same way. They record it in monthly recordings at home. Doctors sometimes still use rituximab for MS.

Regardless of which one you take, the goal is to reduce your B cell count. If it works as it should, you won’t notice anything right away.

“The real benefit we’re looking for isn’t immediate,” says Dr. Ari Green, neurologist at UCSF Health. “It will take years, if not decades. The goal is to prevent long-term disability.”

When should B cell therapy be considered?

B cell therapy prevents disability over time by preventing new damage to your nervous system. It cannot repair damage already done, but it can stop future injuries and attacks.

Within the first few months to a year, Green says, you should notice fewer flare-ups of your MS symptoms. Therapy is even better at preventing new brain lesions from forming.

So, if you’re newly diagnosed, should you go on B-cell therapy?

“There is a debate in the MS world about putting someone who is new to the disease on medications that are considered highly effective, rather than starting them on one of the earlier therapies,” says Julie Fiol, registered nurse and assistant Vice President of Access to Health Care for the National MS Society.

Some doctors may try older medications first to see if they help. That’s partly because they’ve been around longer, so there’s a more extensive track record for their security. If you relapse or get worse, you can switch to B-cell therapy.

“It’s a step-up approach,” says Eric Seachrist, MD, a neurologist at West Virginia University Hospitals who has MS and uses B-cell therapy himself. “You start with the safest but least effective drug and build up when there’s a relapse.”

But he says the newer way of doing things is to use the strongest drugs from the start. This is what he recommends to his patients and what he chooses for himself. The goal is to prevent disease activity and irreparable damage, and hopefully help keep the disease from getting worse.

“Starting with B-cell therapy first provides better disease control and may later delay or prevent secondary progression,” says Seachrist. “But we don’t know the long-term effects on the body of taking super-potent immune-modulating drugs.”

While many doctors are now recommending the B-cell therapy-first approach, there are a few things to consider, Fiol says. Most people do well with B cell therapy. But because it wipes out part of your immune system, it’s associated with an increased risk of infection. The treatment also makes any vaccines you take less effective. And because the drugs haven’t been on the market all that long, the effects of B-cell depletion have been unknown for decades.

Fiol says there is no such thing as a one-size-fits-all approach. She says you should talk to your doctor about the risks and benefits of each option before committing to MS treatment.

How long do you need B cell therapy?

It’s not yet clear if B-cell therapy is forever. But doctors have a clue to its previous use in treating rheumatoid arthritis.

“We know from the arthritis field that if the B cells are depleted for a period of time and then the treatment is stopped, the disease would eventually come back,” says Green. “We think that also applies to MS.”

But, he says, that might only be true if you’re on B-cell therapy for a relatively short period of time. What is less clear is what could happen in the long term. Fiol notes that your immune system changes naturally as you age. As a result, MS can become less active over time.

“In most cases of MS, the peak disease activity in terms of flare-ups that cause inflammation is early, in the first 5 to 10 years or so,” says Seachrist. “So maybe you just need very aggressive therapy for a while and then could de-escalate to something milder for the body. That’s a question in the air.”

Green says the B-cell therapies available today certainly kill more cells than are needed to fight MS. He predicts that treatments could become more specific in the future. Some treatments under investigation also affect B cells in other ways that may prove less risky.

For now, he says, you should expect to use B-cell therapy for years, most likely a decade or more. But as doctors learn more and new treatments become available, that could change.



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