title: Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis.
abstract: Mitoxantrone has been approved by the FDA for worsening relapsing remitting and secondary progressive Multiple Sclerosis. However the benefits of this agent in reducing disease progression and relapse rate cannot be sustained in the long-term, as treatment is limited by the potential for cumulative cardiotoxicity. We report our experience utilising Glatiramer Acetate as maintenance immuno-modulatory treatment following initial immunosuppression with Mitoxantrone in a consecutive series of 27 patients with very active relapsing remitting disease, eight of whom had experienced continuing relapse activity on first-line treatment. Duration of treatment with Mitoxantrone and thereby cumulative dose were reduced as our experience with the combination increased.No unanticipated side effects of combination treatment were encountered over a follow-up period of 66 months. A single patient developed therapy related acute leukaemia (TRAL) 9 months after completion of Mitoxantrone.A sustained 90% reduction in annualised relapse rate (p < 0.001) has been observed. Disability is stable or improved in all patients a mean of 36 (16-66) months from initiation of treatment. Early suppression of relapse activity with Mitoxantrone has been maintained at a mean of 22 months from last dose of this agent. Only two relapses have occurred in the cohort since withdrawal of Mitoxantrone, occurring in the two patients who had previously been treated with Glatiramer Acetate. In 9 of the first 10 patients treated, imaged a mean of 27 months after withdrawal of Mitoxantrone, no enhancing lesions were identified on MRI brain scans. Glatiramer Acetate appears a safe and effective option for continuing disease modification in patients with relapsing remitting multiple sclerosis treated with Mitoxantrone. The treatment protocol utilised in later patients in this series appears to have the potential to limit exposure to this agent.
authors.affiliation: The Walton Centre for Neurology and Neurosurgery, Lower Lane, Liverpool L9 7LJ, UK. j.ramtahal@liverpool.ac.uk
authors.forename: Jason
authors.initials: J
authors.lastname: Ramtahal
authors.forename: Anu
authors.initials: A
authors.lastname: Jacob
authors.forename: Kumar
authors.initials: K
authors.lastname: Das
authors.forename: Mike
authors.initials: M
authors.lastname: Boggild
mesh_terms: D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000700:Analgesics; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D008942:Mitoxantrone