Mitoxantrone for multiple sclerosis
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What is mitoxantrone for MS?
Mitoxantrone hydrochloride is an infusion medication used to slow disability progression and decrease the risk of relapses in people with relapsing forms of multiple sclerosis (MS).
It also is approved for nonactive secondary progressive MS (SPMS), a form of SPMS without relapses with no additional disease-modifying therapies available.
The therapy is available only as a generic medication. It was originally sold under the brand name Novantrone, but Merck KGaA, known as EMD Serono in North America, stopped its distribution after acquiring the medication from Amgen in 2002. This decision was not related to the safety or effectiveness of Novantrone.
Therapy Snapshot
| Brand Name: | Available as a generic medication |
| Chemical Name: | Mitoxantrone hydrochloride |
| Usage: | Disease-modifying therapy for RRMS and SPMS |
| Administration: | Intravenous injection |
How does mitoxantrone work?
MS is caused by the immune system accidentally mounting a response against myelin, the fatty substance that wraps around nerve fibers in the brain and spinal cord. Mitoxantrone is a chemotherapy drug that, in addition to interfering with cell proliferation, also is known to have modulatory effects on the immune system.
The medication particularly suppresses the function of certain immune cells, such as B-cells, T-cells, and macrophages, which are major drivers of inflammation and nerve damage in MS. It also blocks the release of pro-inflammatory signaling molecules.
Through its effects on immune cells, the therapy is thought to reduce damaging inflammation in MS.
Who can take mitoxantrone?
The U.S. Food and Drug Administration approved mitoxantrone in 2000 for the treatment of people with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), with or without relapses. It is the first and only medication approved in the U.S. for SPMS.
The medication is approved in the European Union for people with relapsing forms of MS with highly active disease and rapid worsening in disability for whom no other available treatments exist.
Mitoxantrone also is approved to treat certain forms of cancer. In addition to the U.S. and Europe, it is available in Canada, Australia, South Africa, as well as in several Asian and Latin American countries.
Who should not take mitoxantrone?
Mitoxantrone should not be administered to patients who experienced an allergic reaction to the active ingredient or any other component in the medication.
Among MS patients, the medication also is not recommended for those who:
- have a left ventricular ejection fraction (LVEF), a measure of how much blood is pumped out by the left ventricle with each contraction, below 50%
- experienced a clinically significant reduction in LVEF
- have low levels of neutrophils, a type of immune cell
- have an abnormal liver function
- are pregnant
How is mitoxantrone administered in MS?
Mitoxantrone is administered via an intravenous, or into-the-vein, infusion every three months. Each infusion contains about 12 milligrams of the medication per square meter of body surface area (mg/m²) and takes about five to 15 minutes.
MS patients should not receive a cumulative dose of more than 140 mg/m² over their lifetime. Infusions should be given only by a trained healthcare professional and in a large vein in the arm.
Veins over joints or in extremities should be avoided, and the medication should never be administered by subcutaneous (into-the-skin) or intramuscular (into-the-muscle) injections.
| Administration | Intravenous infusion in a large vein in the arm |
| Dosage | 12 mg/m² |
| Timing | Every three months |
Mitoxantrone in clinical trials
Mitoxantrone’s approvals for MS indications were based on data from two major clinical trials that ran in the 1990s. Both enrolled participants with active and nonactive SPMS, as well as RRMS patients with significant disability between relapses.
Study 1
The first study included 42 patients randomly assigned to receive either a monthly combination of the anti-inflammatory steroid methylprednisolone (1 g) plus mitoxantrone (20 mg) or methylprednisolone alone for six months.
After six months, significantly more patients receiving the combination therapy had no inflammatory lesions, compared with those on methylprednisolone alone (90.5% vs. 31.3%). These patients also had fewer new or enlarging brain lesions and greater improvements in their Expanded Disability Status Scale (EDSS) scores, indicating less disability.
MIMS trial
The second trial, called MIMS, enrolled 149 patients who were assigned to one of two doses of mitoxantrone — 5 or 12 mg/m² — or a placebo, administered every three months for two years. During the trial, patients were allowed to receive a five-day course of methylprednisolone if they experienced a severe relapse.
The trial met its primary goal of showing that the 12 mg/m² dose of mitoxantrone significantly prevented disability progression compared with a placebo. Those on the high dose experienced a 0.13-point decrease in average EDSS scores, indicating less disability, while those on a placebo had worsening disability, or 0.23-point increases in EDSS.
The medication also reduced the amount of severe relapses requiring glucocorticoid treatment, delayed the time to a first relapse, and prevented changes in neurological status — all measures included in the primary outcome.
A number of secondary measures also were met. The higher dose reduced relapse rates (0.35 vs. 1.02 relapses per year) and the proportion of patients who experienced a sustained increase in EDSS scores for at least three months (7% vs. 19%). Patients on the medication also reported less worsening in quality of life and required fewer hospital admissions.
Among patients who underwent regular brain MRI scans, none of those on mitoxantrone had inflammatory lesions at two years, compared with 16% of patients on a placebo. The total number of lesions also was significantly lower in the treatment group.
Common side effects of mitoxantrone
The most common side effects of mitoxantrone in MS clinical trials include:
- nausea
- hair loss
- menstrual problems
- upper respiratory tract infections
- urinary infections
- generalized weakness
Heart problems
Mitoxantrone carries a boxed warning for heart problems. It can lead to heart failure during treatment or months to years after stopping treatment. To mitigate this risk, patients should be monitored for heart health before starting the medication and should not receive the medication if their heart function is compromised.
Leukemia
The boxed warning also includes an increased risk of secondary acute myeloid leukemia in MS patients receiving mitoxantrone. Regular checkups to exclude the development of blood cancer are recommended for these patients.
Low blood cell counts
Mitoxantrone may cause problems in the bone marrow, leading to low levels of several blood cell types, including red blood cells, white blood cells, and platelets. The medication generally is not recommended for patients with low levels of neutrophils, a type of white blood cell involved in fighting infections.
Allergic and injection site reactions
The treatment contains a sulfite called sodium metabisulfite that may cause serious allergic reactions or asthmatic episodes in certain patients. Symptoms should be monitored and treatment discontinued if they occur.
The leakage of mitoxantrone from the vein into the surrounding tissue, called extravasation, may also occur during treatment. This problem normally causes redness, swelling, pain, burning, or blue discoloration of the skin, but it can also result in serious skin damage (necrosis).
Pregnancy and breastfeeding
No adequate and well-controlled studies have examined the effects of mitoxantrone in pregnant people, but animal studies suggest that the medication can cause harm to a developing fetus. Mitoxantrone should not be used during pregnancy, and people who are able to become pregnant should use effective birth control methods while on mitoxantrone.
The medication also is not recommended for use in breastfeeding patients, as significant amounts of the active ingredient have been found in human milk.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about mitoxantrone
Mitoxantrone was approved by the U.S. Food and Drug Administration in October 2000 as a treatment for multiple sclerosis (MS). Indications include secondary progressive MS, with and without relapses, and relapsing-remitting MS with significant symptoms between relapses. However, the medication was first approved in 1987 for a form of blood cancer called acute nonlymphocytic leukemia and in 1996 for prostate cancer.
Based on animal data, mitoxantrone may cause harm to a developing fetus. Patients who are able to conceive should use effective contraception while on treatment and have a negative pregnancy test before each dose. Patients who become pregnant while taking this medication should discuss this issue with their healthcare team.
Interactions between mitoxantrone and alcohol have not been reported. However, alcohol can worsen some side effects associated with this treatment, including diarrhea and mouth sores. Patients on mitoxantrone should discuss safe alcohol use with their healthcare provider.
In one of the trials supporting mitoxantrone’s approval, participants received monthly treatment with either a combination of mitoxantrone plus a steroid medication called methylprednisolone or methylprednisolone alone. After six months, those on mitoxantrone had fewer brain lesions, less disability progression, and fewer relapses. However, because each person reacts to their treatment in differently, it is difficult to predict when someone will start seeing results while on this therapy.
Hair loss, also known as alopecia, is one of the most common side effects associated with mitoxantrone. Weight gain may also occur as a result of heart problems caused by the treatment. Patients who experience any unexpected side effects are advised to talk with their care team.
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