Prädiktoren bei der schubförmigen Multiplen Sklerose im Hinblick auf die Entwicklung einer sekundären Progression

Hintergrund: Im klinischen Verlauf der MS unterscheidet man einen akuten Schub im frühen Stadium von einer chronischen Neurodegeneration in der späten pro-gressiven Phase. Einem Schub liegt eine akute Entzündungsreaktion zugrunde. Mit zunehmender Krankheitsdauer nimmt die Neurodegeneration und eine...

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Main Author: Schloßhauer, Torsten
Contributors: Oertel, Wolfgang H. (Prof. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2010
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Table of Contents: Background: In the clinical course of multiple sclerosis (MS), an acute relapse in the early phase and a chronic neuronal degeneration in the late phase are dif-ferentiated. A relapse is caused by an acute inflammatory reaction. Neuronal degeneration and accumulation of clinical disability of the persons concerned increase with increasing disease duration. During natural course after 10–19 years in two thirds of patients relapsing-remitting MS (RR-MS) transforms into a secondary progressive form of MS (SP-MS). Immunmodulatory treatment of RR-MS with first-line basic therapeutics like interferon beta (IFNß) and glatiramer acetate or copaxone (CPX) is started early in order to inhibit inflammation and to reduce relapse rate and to delay inflammation-dependent disease progression and development of SP-MS. In large controlled clinical trials treatment effects of IFNß and CPX during early clinical course were compared (CHAMPS-,BEYOND-, REGARD- and BECOME-study). The aim of the following observa-tional study was to compare the long-term impact of IFNß and CPX on the de-velopment of SP-MS by survival analysis according to Kaplan-Meier. Methods: A total of 777 patients were screened retrospectively for the following inclusion criteria: (1) RR-MS according to McDonald, (2) IFNß or CPX as first-line and monotherapy for at least 9 months or change of treatment within 9 months for side effect reasons (3) disease duration between diagnosis and treatment initiation  5 years (4) current EDSS  5. Exclusion criteria were: (1) development of SP-MS before or within 6 months after the start of treatment (2) change of treatment because of treatment failure. SP-MS was defined as dis-ease progression in a sense of deterioration of EDSS by 0.5 points within 6 months. The following primary outcome measures were compared: (1) percentage of patients with RR-MS after follow-up of 6 years or patients who developed SP-MS, (2) mean worsening of basic-EDSS during this period. Statistical analysis was performed by survival analysis to Kaplan-Meier, Cox-Regression-analysis and Blox-plot using SPSS programme 15.0 (SPSS inc., Chicago, Illinois). Sig-nificance was calculated using Log-Rank-Test and p-values  0.05 were consid-ered to be significant. Results: A total of 388 patients with RR-MS were included in this study. 264 pa-tients were treated for 6 years with IFNß and 124 patients received CPX. At the beginning of treatment no distinct differences in demographic and clinical char-acteristics (proportion of women, age, EDSS and disease duration) were seen between treatment groups. During 6 years after start of therapy the percentage of patients with RR-MS weren’t significantly different for both therapy regimen (CPX: 104/124 or 83.9 % vs IFNß: 212/264 or 80,3 %; p = 0.39). In the CPX-group 20/124 or 16.1 % of patients developed SP-MS and 52/264 or 19.7 % of patients in the IFNß-group. Hazard-analysis didn’t show any significant differ-ence between both drugs (p=0.39). Using these data and values of power, level of significance and clinical relevant difference, sample size of a prospective trial was calculated to be 3000 – 4000 for both groups. Conclusions: Long-term treatment effects of IFNß and CPX were comparable with respect to development of SP-MS. There were no clinically relevant differ-ences between both drugs (p=0.39). Potential clinical differences between these basic therapeutics can be demonstrated in a prospective trial with calculation of sample size and power of 80 %.