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Induction and Escalation Therapies for MS

Medically Reviewed by Christopher Melinosky, MD on May 03, 2022

Multiple sclerosis (MS) is a chronic neurologic disease where your body’s immune system attacks your central nervous system, especially the protective coating around your nerves. This coating is called myelin. Without it, your brain’s nerve impulses slow down or even stop. MS can also directly damage the nerves underneath the coating. Both brain inflammation and nerve damage cause the symptoms of MS.

To treat MS, doctors do a few different things. They use medicines to treat symptoms like inflammation. They also use medicines to prevent relapses, for example, in people with relapsing-remitting MS. That form of the disease comes and goes and is caused by bouts of inflammation. For all types of MS, including primary and secondary progressive MS – which get worse over time and involve damage to the nerves themselves – doctors use disease-modifying drugs (DMDs). DMDs address MS directly to slow down its progression.

There are two ways doctors usually approach treatment, depending on the nature of a person’s MS. These are induction therapy and escalation therapy. In both cases, experts say treatment should be started as early as possible. The difference is in how aggressive the very first treatment is.

What Is Escalation Therapy?

Escalation therapy is the standard approach for most people with MS. With escalation therapy, your doctor will start you on certain DMDs, often taken by injection (beta-interferons, glatiramer acetate), either from a doctor or at home. You can also get DMDs in a pill form (dimethyl fumarate, teriflunomide). These DMDs have a good balance between effectiveness and risks of side effects, which are relatively low. You may feel like you have the flu after your injection. This usually goes away after a couple of days. You may also have some irritation at the spot where you got the injection. For more aggressive MS, your doctor will start with slightly more powerful DMDs. There are more than a dozen drugs approved for relapsing-remitting MS, which is the most common type. About 85% of people with MS are first diagnosed with this form of MS.

You’ll move to more and more powerful treatments as needed if the previous treatment isn’t working. Each of these will have more risks of side effects. The idea behind escalation therapy is to find the perfect balance of effectiveness and safety for each patient’s unique disease. While this ensures long-term safety of the drug, you also run the risk of your disease reactivating.

What Is Induction Therapy?

With induction therapy, your doctor will start you off with stronger drugs or therapies. These include powerful immune-suppressing drugs, many of which are also used to treat cancer. Some drugs are taken in tablet form, while others are injected or given through an IV in the hospital. Some of these are given during escalation therapy too, but not until later in treatment – either because you have severe MS or because your MS did not respond to milder approaches.

Induction may also start with a stem cell transplant using your own bone marrow. This is a one-time procedure. The doctor collects blood stem cells from your bone marrow. Then, they store them while you have chemotherapy to slow down your immune system. The doctor then gives you back your stem cells through an IV. It is thought to give your immune system a “reboot” by wiping it out and rebuilding it. These transplants are for people under 50 with severe MS who have had the disease for less than 10 years.

Induction therapy is meant to strongly slow down your immune system first. Then you would continue on maintenance treatment with less powerful drugs to keep your immune response in check. Some studies have shown that people are less likely to develop long-term disability with a more aggressive path at the beginning.

When Is Induction Therapy Used?

Bouts of inflammation are often at the root of MS in its early stages. But this can develop into secondary progressive MS. This involves more severe symptoms and nerve damage that gets worse over time and can’t be reversed. Experts who use induction therapy believe that by targeting the inflammation from the get-go, they have the best chance of keeping the disease from slipping into that second, long-term phase.

Induction therapy may be too aggressive for some patients. Usually, induction is used on people whose MS is very active. That might mean that they have serious relapses often, or that they have lots of nerve damage seen on an MRI. Or maybe their MS hasn’t responded to other treatments. These people are at greater risk of developing disabilities more quickly.

The best time for induction therapy in these patients, according to experts, is during a bout of inflammation but before the disease has done permanent damage.

What Are the Risks of Induction Therapies?

Induction drugs can be effective. Some have been shown to cut relapses by more than 50% compared to safer drugs. But there are many common side effects that often need medical attention. These include:

  • Abnormal urine and bowel movements
  • Cough, shortness of breath, or chest tightness
  • Fainting and dizziness
  • Abnormal heartbeat
  • Back, side, stomach, joint, or mouth pain
  • Unusual bleeding or bruising
  • Fatigue or weakness
  • Fever or chills
  • Missing menstrual periods
  • Confusion or agitation
  • Headaches
  • Itching
  • Nausea or vomiting
  • Swollen glands
  • Sweating
  • Red “pinprick” spots on skin
  • Hair loss
  • Infection due to a weakened immune system

There is also a long list of more minor side effects with these drugs that don’t need medical attention but are common and uncomfortable. Ask your doctor about these at your next visit.

If you have a bone marrow transplant, it is an intensive process. Removing your stem cells takes a week or two, and you will then stay in the hospital for a few weeks. This leaves you time to prepare your immune system, get your stem cells back, and recover. You will also go to frequent follow-up visits for a couple of years after your transplant.

The effectiveness of this procedure varies a lot. Some people go into full, long-term remission. Some have even recovered some abilities they’d lost. But the procedure also poses several serious risks, some of which can be life-threatening. These include:

  • Infection because your immune system is weakened
  • Sepsis, a dangerous complication of an infection
  • Irritated mouth and digestive tract
  • Lung or kidney problems
  • Infertility
  • Loss of mobility as a result of muscle weakness from chemotherapy
  • Cognitive problems

There is no right answer for whether an induction or escalation path is better. Talk with your doctor about which is right for you and the unique nature of your MS.

Show Sources

SOURCES:

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry: “Induction and Escalation Therapies in Multiple Sclerosis.”

Cancer Research UK: “Alemtuzumab (Campath, MabCampath),” “Cyclophosphamide,” “Mitoxantrone (Mitozantrone),” “Rituximab (Mabthera, Rixathon, Truxima).”

Cedars-Sinai: “Progressive-Relapsing MS (PRMS).”

CNS Drugs: “Induction Therapy for Patients with Multiple Sclerosis: Why? When? How?”

European Committee for Treatment and Research in Multiple Sclerosis, London, Sept 14-17, 2016: “The Initial Treatment of Early Active Relapsing Remitting MS Should Be with a Potent Induction Therapy Rather Than Standard Immunomodulation then Escalation.”

Frontiers in Immunology: “Immunological Aspects of Approved MS Therapeutics.”

Mayo Clinic: “Alemtuzumab (Intravenous Route),” “Cladribine (Intravenous Route),” “Cyclophosphamide (Oral Route, Intravenous Route),” “Mitoxantrone (Intravenous Route).”

Multiple Sclerosis and Demyelinating Disorders: “Induction Treatment Strategy in Multiple Sclerosis: a Review of Past Experiences and Future Perspectives.”

Multiple Sclerosis Society UK: “Alemtuzumab (Lemtrada),” “Beta Interferons,” “Cladribine (Mavenclad),” “HSCT,” “Ocrelizumab.”

National Multiple Sclerosis Society: “AHSCT in MS (Autologous Hematopoietic Stem Cell Transplantation),” “FAQ About HSCT (Hematopoietic Stem Cell Therapy) in MS,” “Types of MS.”

Neurotherapeutics: “Commentary: The Multiple Sclerosis Controversy: Is It Escalation or Induction High Efficacy?”

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