Highlights
- •Mitoxantrone is an effective treatment for relapsing-remitting multiple sclerosis.
- •Mitoxantrone has a well-established risk profile.
- •Mitoxantrone is a low-cost drug which can be beneficial in low income settings.
Abstract
Background
Mitoxantrone (MTX) has been used as an effective disease modifying treatment (DMT)
in multiple sclerosis (MS). Evidence from studies demonstrates benefits of reduced
relapse rates, MRI disease activity and disability progression in patients treated
with MTX. While effective, MTX use has been limited due to potential adverse effects
(AE) ranging from mild to potentially life-threatening AEs such as cardiotoxicity,
bone marrow suppression and hematological malignancies. In this study we aimed to review the long-term clinical efficacy, tolerability, and
AE profile of treatment with MTX in patients both with relapsing-remitting and rapidly
progressive MS over a 10-year follow-up period.
Methods
We collected prospective data of 70 patients with relapsing-remitting and rapidly
progressive MS treated with MTX and followed-up over a 10-year period. Expanded disability
status scale (EDSS) scores and annualized relapse rates (ARR) were assessed 1 year
prior to MTX treatment, and at different time points (1, 2, 3, 5 and 10 years) during
follow-up. We recorded the time to first relapse and 0.5-point EDSS increase to assess
efficacy. We also obtained frequency data on AEs and patients withdrawn from treatment.
Results
70 patients were started on treatment with MTX with 53 patients (34 relapsing-remitting
MS, 19 progressive disease) completing the course. Mean EDSS progressed from 5.5 to
6.5 in the relapsing-remitting group and 6.7 to 9.0 in the progressive group over
the study period. ARR in the RRMS group reduced at all time points from 2.2 prior
to MTX to 0.3 by year 10. We reported 3 significant AEs, one chicken pox and subsequent
acute promyelocytic leukemia, one left ventricular systolic dysfunction, one pancytopenia.
The commonest AE reported was nausea/vomiting in 28 (40%) patients. Seventeen patients
(5 relapsing-remitting, 12 progressive disease) stopped treatment. In fifteen (87%)
of these this was due to lack of efficacy. In the remaining 2 patients, MTX was stopped
due to one patient developing chicken pox and the other developing first-degree heart
block.
Conclusion
Our study demonstrated that MTX is an effective disease modifying treatment for relapsing-remitting
MS with a well-established risk profile. While MTX is now used less frequently, many
MS and neurology services continue to follow-up patients who have been treated with
MTX previously. Therefore, understanding the long-term effects risks and benefits
remains relevant in this patient group. MTX is also a low-cost treatment in comparison
to other high efficacy MS disease-modifying treatments and this may be beneficial
in low resource settings.
Keywords
Abbreviations:
mtx (mitoxantrone), Ae (adverse effect), Ms (multiple sclerosis), Rrms (relapsing-remitting multiple sclerosis), Dmt (disease-modifying treatment), Edss (expanded disability status scale), Arr (annualized relapse rate), Apl (acute promyelocytic leukemia), LVSD (left ventricular systolic dysfunction)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 23, 2020
Accepted:
June 21,
2020
Received in revised form:
June 15,
2020
Received:
March 26,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
