Combination Intravenous Therapies in the Treatment of Multiple Sclerosis

By Administrator

Amie Pena, NP–Barrow Neurology Clinics, Phoenix, Arizona

Introduction

As patients and caregivers we are all aware that multiple sclerosis (MS) is a complex, chronic disease. Just a few decades ago, the outlook for patients with MS was poor and there were no treatments to help reduce disease progression. Many patients were told, “You have MS and there is nothing I can do for you. Go home and live your life.”

The evolution of treatment for MS has come a long way since then. We now have Food and Drug Administration (FDA)-approved self-injecting medications that help reduce disease activity and slow down progression of disability. The FDA-approved injectable therapies for relapsing-remitting MS include glatiramar acetate (Copaxone), interferon-B-1a (Rebif), interferon-B-1a (Avonex) and interferon-B-1b (Betaseron), all of which are identified as MS disease-modifying therapies (DMTs). In recent years, research in the field of MS has expanded and we have learned that combining these DMTs with intravenous (IV) medications can enhance efficacy, resulting in significantly improved patient outcomes. Combination IV therapies are ever increasing in the treatment of MS and with continuing research may represent a suitable therapy choice for many patients with MS.

There is little public information addressing MS infusion therapy. Due to this lack of information, many patients with MS are uneducated on the subject of common IV MS drug therapies, their side effects (SEs), risks, and expectations. This often results in uncertainty and angst. The information provided in this article is written to help minimize patient fears and anxiety that come from the uncertainty of what to expect with standard IV MS medications.

What is Infusion Therapy?

Infusion therapy involves the administration of IV medications directly into the bloodstream through a vein, usually in the arm. In the case of MS, these medications go from the bloodstream into the central nervous system (CNS) where they help to shut off inflammation and prevent further damage. This can result in fewer relapses, reduction in MRI lesions and ultimately, less disability (Hartung et al., 2002; Achiron et al., 1998; Miller et al., 2003; Durelli et al., 1986; Zephir et al., 2004).

Who is Appropriate for Combination IV Infusion Therapy?

There are several circumstances when IV medications are initiated. In rare instances they are used when patients are unable to tolerate the FDA-approved injectable DMTs. More often, they are used in patients who continue to progress or worsen despite being on an injectable DMT. These are patients who are classified as secondary progressive MS or worsening MS (Hartung et al., 2002; Weiner & Cohen, 2002; Zephir et al., 2004). This does not mean that all patients are candidates for IV infusion therapy. It is important to keep in mind that the majority of patients with MS respond very well to the DMT injectable therapies and do not require combination drugs. The IV drugs are reserved only for those patients who require more aggressive therapy.

What Types of Infusion Drugs are Used in the Treatment of MS?

MS IV infusion therapy drugs can be classified into four different categories:

1. Immunosuppressants
Solumedrol (methyprednisolone) and Decadron (dexamethasone) are comparable IV steroid drugs. They are frequently used to shut off inflammation associated with acute relapses. They are also commonly used in combination with the injectable DMTs to help stabilize patients with MS who are progressing at a rapid rate. These drugs are typically given once a day for 3 days for a mild relapse and 5 days for more severe relapses. As more of a maintenance therapy for patients with worsening MS, these drug infusions are given repeatedly for three consecutive days every 1 to 3 months, depending on the patient (Buckley, Kennard,
& Swash, 1982).

2. Chemotherapy-Immunosuppressants
The two common chemothearpy drugs used in the treatment of MS are mitoxantrone (Novantrone) and cyclophasphamide (Cytoxan). They are used in patients with secondary progressive as well as worsening MS. These chemotherapy drugs help to slow the progression of the disease and decrease the rate of disability by suppressing the immune system and decreasing the number of circulating inflammatory T cells that attack the myelin in the CNS of the patient with MS. Because these chemotherapy drugs suppress the immune system, they can have rare but serious side effects and risks associated with them. The risks and side effects of chemotherapies will be discussed later in this article. These chemotherapy drugs are typically infused every 3 to 6 months for as long as needed. (Hartung et al., 2002; Weiner et al., 2002).

3. Immunomodulators
Intravenous immunoglobulin (IVIG) is an immunomodulator that is used in the treatment of MS. IVIG binds to parts of the T-cells and helps to suppress and neutralize inflammatory cytokines in the CNS. This can result in fewer relapses and less disability in the patient with MS. This drug is typically given initially as a 5-day consecutive infusion and then only once a day every month thereafter (Sorenson 2003; Achiron et al., 1998).

4. Monoclonal Antibodies
Tysabri is a new monoclonal antibody that was recently taken off of the market, secondary to three reports of progressive multifocal leukoencephalopathy (PML) in study patients who were on combination therapy, including interferon beta1a (Avonex) in addition to Tysabri. Two patients died as a result of PML. The drug is no longer available clinically, but the FDA has given recent approval for Tysabri research to resume. Information will be released in the near future regarding its use in the clinic. This monoclonal antibody works by binding to a part of the T-cell preventing it from migrating into the CNS. In the studies thus far, it has shown to be effective in decreasing gadolinium enhancing “active” lesions on MRI and disability. This drug is given once a month (Miller et al., 2003).

What are the Side-Effects and Risks With These IV Therapies?

With any medication, there are always side-effects and risks. That is why it is always important to discuss these therapies with your health care provider to decide whether or not this is an appropriate medication for you or your loved one. The side-effects of these infusion medications are self-limiting and can often be controlled and minimized. As you read this section please keep in mind that these IV infusion therapies are generally well tolerated and can favorably affect the course of disease. Table 1 lists the common, rare, and very rare side effects that can occur with these drugs. Techniques used to help minimize and combat these side-effects are also included.

How Long Will These Infusions Take?

Infusion times vary with each drug. Listed below are the actual infusion times for each drug. You need to remember to allow approximately 15-30 additional minutes for check-in, insertion of your IV, and vital signs.

Solumedrol and Decadron: 1 hr

Novantrone: 1 hr

Cytoxan: 2.5 hours

IVIG: 2 to 4 hour (depending on the dose)

Tysabri: 2 hours (1 hr for infusion and 1 hr
for post-infusion monitoring)

What Should I Expect the Day of My Infusion?

When you arrive for your infusion the nurse will take your temperature and vital signs and ask you some brief questions to make sure that it is safe to proceed with the infusion that day. She will insert an IV to your arm, which will feel similar to having your blood drawn. Once the IV is established your medication will be infused at the proper rate. It is important for you to notify your nurse at anytime if your IV or arm begins to feel uncomfortable or if you begin to experience any side-effects. The infusion can be slowed or stopped as needed. Once your infusion is complete your vital signs will be repeated.

What Side-Effects or Problems Should I Alert My Provider About?

It is imperative that you alert your provider should you have any signs or symptoms of infection. These include, fever, chills, burning with urination, blood in your urine, persistent cough, and common cold symptoms. Other symptoms to notify your provider about include nausea and vomiting, rashes or anything out of the ordinary following your infusion.

How Long Will It Take for These Drugs to Work?

Steroids commonly take up to 7 days to see an improvement in symptoms, although many patients report feeling better after only a few days (Durelli et al. 1986). Chemotherapies typically take a little longer to see their stabilizing effects, usually about 6 to 12 months. The effects of IVIG and Tysabri typically are seen in 2 to 6 months (Sorenson 2003; Achiron et al., 1998; Miller et al., 2003). It is important to set realistic expectations with these drugs. The purpose of these drugs is not to make patients better, but to help slow down their rate of disease and disability. These drugs are not 100% effective and are not a cure, but they do significantly slow the rate of disease progression.

References

Achiron, A., Gabbay, U., Gilad, R., Hassin-Baer, S., Barak, Y., Gornish, M., et al. (1998). Intravenous immunoglobulin treatment in multiple sclerosis. Neurology, 50(2), 398-402.

Buckley, C., Kennard, C., & Swash, M. (1982). Treatment of acute exacerbations of multiple sclerosis with intravenous methylprednisolone. Journal of Neurology, Neurosurgery and Psychiatry, 45, 179-180.

Durelli, L., Cocito, A., Riccio, A., Barile, B., Bergamasco, B., Baggio, G.F., et al. (1986). High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: Clinicalimmunologic correlations. Neurology, 36, 238-243.

Hartung, H. P., Gonsette, R., Konig, N., Kwiecinski, A. G., Morrissey, S. P., Krapf, H., et al. (2002). Mitoxantrone in progressive multiple sclerosis: A placebo-controlled, double-blind, randomised, multicentre trial. Lancet, 360, 2018-2025.

Miller, D. H., Khan, O. A., Sheremata, W. A., Blumhardt, L. D., Rice, G. P .A., Libonati, et al. (2003). A controlled trial of natalizumab for relapsing multiple sclerosis. New England Journal of Medicine, 348, 15-23.

Sorenson S. (2003). The role of intravenous immunoglobulin in the treatment of multiple sclerosis. Journal of the Neurological Sciences, 206, 123-130.

Weiner, H. L. & Cohen J. L. (2002). Treatment of multiple sclerosis with cyclophosphamide: Critical review of clinical and immunologic effects. Multiple Sclerosis, 8, 142-154.

Zephir, H., de Seze, J. Duhamel, A., Debouverie, M., Hautecoeur, P., Lebrun, C., et al. (2004). Treatment of progressive forms of multiple sclerosis by cyclophosphamide: a cohort study of 490 patients. Journal of the Neurological Sciences, 218, 73-77.

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