This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Jeffery, D. R Articles by Burdette, J. Search for Related Content PubMed PubMed Citation Articles by Jeffery, D. R Articles by Burdette, J. Social Bookmarking                         What's this?

A pilot trial of combination therapy with mitoxantrone and interferon beta-1b using monthly gadolinium-enhanced magnetic resonance imaging

Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA, djeffery{at}wfubmc.edu

Neraj Chepuri

Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

David Durden

Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

Jonathon Burdette

Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

Objective: To examine the safety of combination therapy with mitoxantrone (MITX) and interferon ß-1b (IFNß-1b) in patients with multiple sclerosis (MS) and a high on-therapy relapse rate and enhancing lesions on baseline magnetic resonance imaging (MRI) scan. Methods: Ten patients with worsening relapsing—remitting or secondary progressive MS were studied using monthly MRI with triple-dose gadolinium contrast. All patients must have been on IFNß-1b for at least six months, have at least one enhancing lesion on a screening MRI, at least one relapse on IFNß-1b in the six months prior to study entry and be neutralizing antibody negative. Monthly MRI scans using triple dose contrast and a 30-minute delay between contrast administration and scanning were carried out three times over two months to obtain baseline numbers of enhancing lesions each month. At the end of the baseline phase, MITX was administered at 12 mg/m² (month 3), and 5 mg/m² at months 4 and 5. Dosing was continued at 5 mg/m² every third month. Monthly MRI scanning was continued throughout the duration of MITX dosing. The primary outcome measure was the frequency of new enhancing lesions. Secondary outcome measures included relapse rate, and T1 hypointense and T2 lesion burden. Results: Following the addition of MITX to IFNß-1b mean enhancing lesion frequency decreased 90% at month 7 (P=0.008) and enhancing lesion volume decreased by 96% (P=0.01). Relapse rates decreased 64% (P=0.004). T2 lesion burden and T1 hypointense lesion burden increased slightly during the baseline phase and decreased following MITX but the difference did not reach statistical significance. There were no serious adverse events on combination therapy and no drop-outs due to toxicity. Total white blood cell count was reduced at 14 days post-MITX infusion but returned to normal levels by day 21. There were no neutropenic fevers and there was no clinically significant elevation of liver function tests. Conclusions: While the number of patients in this study was small, the results suggest that the combination is safe and well tolerated. Disease activity was substantially reduced following the addition of MITX to IFNß-1b.

Key Words: gadolinium-enhancing lesions • interferon beta-1b • magnetic resonance imaging • mitoxantrone • multiple sclerosis • suboptimal response

Multiple Sclerosis, Vol. 11, No. 3, 296-301 (2005)
DOI: 10.1191/1352458505ms1154oa


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. Rieckmann, A. Traboulsee, V. Devonshire, and J. Oger Review: Escalating immunotherapy of multiple sclerosis Therapeutic Advances in Neurological Disorders, November 1, 2008; 1(3): 181 - 192. [Abstract] [PDF]

				C. A. Foster, L. M. Howard, A. Schweitzer, E. Persohn, P. C. Hiestand, B. Balatoni, R. Reuschel, C. Beerli, M. Schwartz, and A. Billich Brain Penetration of the Oral Immunomodulatory Drug FTY720 and Its Phosphorylation in the Central Nervous System during Experimental Autoimmune Encephalomyelitis: Consequences for Mode of Action in Multiple Sclerosis J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 469 - 475. [Abstract] [Full Text] [PDF]

				M. S. Cartwright, D. R. Jeffery, Z. T. Lewis, P. P. Koty, W. T. Stewart, and I. Molnar MITOXANTRONE FOR MULTIPLE SCLEROSIS CAUSING ACUTE LYMPHOBLASTIC LEUKEMIA Neurology, May 8, 2007; 68(19): 1630 - 1631. [Full Text] [PDF]