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Optimization of the Efficacy of Interferon Beta1α and Azathioprine Combination Therapy in Multiple Sclerosis

Author: FengMeiNa
Tutor: ZhangZuo
School: Huazhong University of Science and Technology
Course: Neurology
Keywords: multiple sclerosis azathioprine beta-interferon combined therapy
CLC: R744.51
Type: Master's thesis
Year: 2013
Downloads: 4
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Purpose:to investigate the efficacy and safety of interferon beta la and azathioprine combination therapy in relapsing-remitting multiple sclerosis in order to better define what factors might predict tolerability and response.Methods:We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-Bla combined therapy in patients with clinically definite RRMS, who had not previously been responsive to either monotherapies. Our cases were divided into three subgroups:previously untreated patients (subgroup A) with at least6months of natural course of the disease,patients (subgroup B) previously treated with AZA for6months and patients (subgroup C) previously treated with IFN-β1α6months. All patients in subgroup B and C completed more than6months of combined treatment with AZA and IFN-β1α, and all patients in subgroup A did not accept any drugs. The clinical endpoints were:(1) number of relapses,(2)MRI endpoints:the MRI endpoints were the change in the number of T1hypoin-tense, FLAIR hyperintense and enhanced T1lesions.(3) EDSS scores, and (4) the tolerability and safety of interferon beta laand azathioprine. The effect of treatment was analysed using t-test and correlation analysis.Result:eighty-one patients were qualified for the combination. Six individuals were lost to follow up. eleven patients were dropped because of expensive medical expenses and fears of side effects. Of these only64patients ultimately met all the eligibility criteria and agreed to initiate combination therapy,and completed the study.The average age of them was33.781±1.078.There was no significant difference between the relapses, the number of MRI lesions and EDSS scores before initiation of treatment (P>0.05). The number of relapses during the combined treatment period was significantly lower than that of the previous either monotherapies:in subgroups B and C, there were78.837%and89.124%reduction in the number of relapses(P=0.000, P=0.000). In subgroup A, there was a3.226%rise (P>0.05). In subgroups B and C,mean EDSS score during combined treatment was also significantly lower than that of the s ame previous period. After2year of experimentation, AZA+INF-β1α combination therapy appears to be safe; no serious side effects have been seen. However, combined treatment did not significantly reduced the number of T1lesions and the number of FLAIR lesions compared with those during the same period of monotherapy in both subgroups B and C,and the number of gadolinium-enhanced T1lesions decreased in subgroups B and C.The relationship between the total AZA dose (mg), relative AZA dose (mg/kg body weight),6-TGN levels, WBC and Gd/MRI lesions was investigated. As predicted, there was no correlation between AZA dose and Gd/MRI lesions and only a trend with6-TGN (r=-0.570, P=0.011). Remarkably, there was a strongly significant positive correlation between total WBC and Gd/MRI lesions (r=0.750, P=0.000).Conclusions:Inflammatory activity can not be completely suppressed, but combination therapy with IFNb-1b and AZA resulted in a significant reduction in the number of relapses and disability. The combination was safe in most MS patients. We conclude that those who can tolerate doses to reduce the WBC below4.8×109/L seem to benefit the most in the acute setting, simultaneous detection of its metabolites6-TGN guided medication, to avoid the occurrence of serious adverse reactions.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Spinal cord disease > Demyelinating disease > Multiple sclerosis
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