B-Cell Therapy: The Long-Term Effects
By Kendall K. Morgan
When you have multiple sclerosis (MS), your immune system works against you. Left unchecked, immune cells attack the protective layer that surrounds your nerve fibers. Doctors used to think your immune T cells were the main culprit in this. Immune B cells, which make antibodies, were considered innocent bystanders.
That changed as scientists started to realize that the existing MS treatments worked in part by changing what B cells were doing. Would it be possible to treat MS by targeting B cells directly?
Doctors already had a way to do it: an antibody-based treatment called rituximab, used to fight a type of cancer called B-cell lymphoma. A 2008 study showed rituximab did help people with MS. After 48 weeks, people in the study had fewer brain lesions and avoided relapses, too.
The FDA approved a drug similar to rituximab, called ocrelizumab (Ocrevus), for MS in 2017. You get it through an IV once every 6 months. In 2020, the FDA approved another drug, called ofatumumab (Kesimpta), that works the same way. You take it in monthly shots at home. Doctors sometimes still use rituximab for MS, too.
No matter which one you take, the goal is to reduce the number of B cells you have. When it works the way it should, you won’t notice anything right away.
“The real benefit we’re looking for isn’t immediate,” says Ari Green, MD, a neurologist at UCSF Health. “It takes place over years, if not decades. The goal is to prevent long-term disability.”
When to Consider B-Cell Therapy
B-cell therapy prevents disability over time by preventing new harm to your nervous system. It can’t fix damage that’s already there, but it can stop future injury and attacks.
Within the first few months to a year, Green says, you should notice fewer relapses of your MS symptoms. The therapy does an even better job of keeping new brain lesions from forming.
So, if you’re newly diagnosed, should you take B-cell therapy?
“There’s a debate in the MS world about starting somebody who is new in the disease on medication that’s considered high-efficacy versus starting them on one of the earlier therapies,” says Julie Fiol, a registered nurse and associate vice president of health care access for the National MS Society.
Some doctors may try older drugs 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 safety. If you relapse or get worse, you can move up 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 takes B-cell therapy himself. “You start with the safest but least effective medicine and bump up if there’s a relapse.”
But he says the newer way of doing things is to use the strongest medicines from the beginning. This is what he recommends for 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 on B-cell therapy first controls the disease better and can delay or prevent secondary progression later,” Seachrist says. “But we don’t know the long-term effects on the body from taking super-strong immune-modulating medicines.”
While many doctors now recommend the B-cell-therapy-first approach, there are some things to consider, Fiol says. Most people do well on B-cell therapy. But because it wipes out part of your immune system, it comes with an increased risk for infection. The treatment also makes any vaccines you take less effective. And since the drugs haven’t been around that long, the effects of depleting B cells over decades aren’t yet known.
Fiol says there’s no “one-size-fits-all approach.” She says you should talk with your doctor about the risks and benefits of each option before deciding on an MS treatment.
How Long Will You Need B-Cell Therapy?
It’s not yet clear whether B-cell therapy is forever. But doctors do have some clue from its earlier use in treating rheumatoid arthritis.
“We know from the arthritis field, if B cells are depleted for a time and then treatment is stopped, ultimately the disease would come back,” Green says. “We think that’s true in MS, too.”
But, he says, that may only be true if you get B-cell therapy for a relatively short time. It’s less clear what could happen over the long term. Fiol notes that your immune system naturally changes as you age. As a result, MS can become less active over time.
“In most cases of MS, the highest disease activity as far as inflammation-causing relapses is early, the first 5 to 10 years or so,” Seachrist says. “So maybe you only need highly aggressive therapy for a time and then you could de-escalate to something milder on the body. That’s a question that’s up in the air.”
Green says that the B-cell therapies available today surely wipe out more cells than is necessary to control MS. He predicts that in the future, treatments may become more specific. Some treatments now being studied also affect B cells in other ways that may prove less risky.
For now, he says, you should anticipate using B-cell therapy for years, most likely a decade or longer. But as doctors learn more and new treatments become available, this could change.
Photo Credit: Digital Vision / Getty Images
Ari Green, MD, neurologist; medical director, Multiple Sclerosis Center, UCSF Health, San Francisco.
Eric Seachrist, MD, neurologist; assistant professor, West Virginia University School of Medicine, Morganton.
Julie Fiol, registered nurse; associate vice president for health care access, National MS Society.
Mayo Clinic: “Multiple Sclerosis.”
Frontiers in Oncology: “Past, Present, and Future of Rituximab — The World’s First Oncology Monoclonal Antibody Therapy.”
Nature Reviews Drug Discovery: “B cell depletion therapies in autoimmune disease: advancesand mechanistic insights.”
Nature: “Targeting B cell leads to breakthrough therapy.”