Compliance and efficacy of mitoxantrone in clinical practice.
|Title||Compliance and efficacy of mitoxantrone in clinical practice.|
|Publication Type||Journal Article|
|Authors||Wundes A, Kraft GH, Bowen JD, Gooley TA, Nash RA|
Background: Management of worsening multiple sclerosis (MS) continues to pose a major therapeutic challenge. Mitoxantrone has been approved for worsening MS and its efficacy has been demonstrated in trials. Because of side effects, non-compliance and other reasons the standard protocol of 12 mg/m2 every 3 months for up to 140 mg/m2 is not always followed. The purpose of this study is to evaluate the results of using mitoxantrone under these conditions. Objectives: (1) Examine deviations from the standard protocol. (2) Determine reasons for alterations of mitoxantrone regimen. (3) Determine under these conditions, if mitoxantrone is therapeutically beneficial. Methods: We retrospectively analyzed data from 96 consecutive patients starting mitoxantrone for worsening MS between 9/1999 and 6/2005 in an academic multi-disciplinary MS Center. Results: 64 patients (67%) did not receive the intended mitoxantrone regimen. Of these, 31 discontinued prematurely due to discouragement or poor tolerability. Fewer patients stopped for safety reasons (asymptomatic LVEF reduction n = 7, thrombocytopenia n = 1). For the 96 patients studied, the annualized relapse rate (ARR) was 1.07 during the 24 months pre-treatment. It was reduced to 0.54 (p = 0.006) during (mean observation time 20 months), and to 0.46 (p < 0.001) in the follow-up period (mean 20 months) after discontinuation of mitoxantrone. Seventy-one patients were further stratified based on the number of mitoxantrone infusions (1–3, 4–7, = 8). ARR was reduced in all groups, but only for patients receiving = 8 infusions statistical significance (p = 0.001) was reached. Patients were relatively stable with regard to the Expanded Disability Status Scale (EDSS) during mitoxantrone treatment. The mean change of the EDSS was + 0.22 (p = 0.004). Conclusion: In the clinical setting, despite frequently incomplete treatment schedules, mitoxantrone stabilizes disease activity in patients with worsening MS. Neurological function in patients was stabilized and relapse rates were reduced. Our data suggest that patients who receive less than full dose still derive some benefit from mitoxantrone. However, for maximum clinical benefit a full dose appears to be needed.