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10.1212/NXI.0000000000000360 http://scihub22266oqcxt.onion/10.1212/NXI.0000000000000360 C5459792!5459792!28626781     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Neurol+Neuroimmunol+Neuroinflamm 2017 ; 4 (4): ä Nephropedia Template TP {{tp|p=28626781|t=2017. Both cladribine and alemtuzumab may effect MS via B-cell depletion |pdf=|usr=}}{{28626781}} gab.com Text Both cladribine and alemtuzumab may effect MS via B-cell depletion JO: Neurol Neuroimmunol Neuroinflamm http://www.kidney.de/pget.php?&tw=1&pmid=28626781 #FOAvip Objective:: To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies. Methods:: The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests. Data were extracted and statistically analyzed. Results:: Either dose of cladribine (3.5 mg/kg; 5.25 mg/kg) tested in CLARITY reduced the annualized relapse rate to 0.16?0.18 over 96 weeks, and both doses were similarly effective in reducing the risk of MRI lesions and disability. Surprisingly, however, T-cell depletion was rather modest. Cladribine 3.5 mg/kg depleted CD4+ cells by 40%?45% and CD8+ cells by 15%?30%, whereas alemtuzumab suppressed CD4+ cells by 70%?95% and CD8+ cells by 47%?55%. However, either dose of cladribine induced 70%?90% CD19+ B-cell depletion, similar to alemtuzumab (90%). CD19+ cells slowly repopulated to 15%?25% of baseline before cladribine redosing. However, alemtuzumab induced hyperrepopulation of CD19+ B cells 6?12 months after infusion, which probably forms the substrate for B-cell autoimmunities associated with alemtuzumab. Conclusions:: Cladribine induced only modest depletion of T cells, which may not be consistent with a marked influence on MS, based on previous CD4+ T-cell depletion studies. The therapeutic drug-response relationship with cladribine is more consistent with lasting B-cell depletion and, coupled with the success seen with monoclonal CD20+ depletion, suggests that B-cell suppression could be the major direct mechanism of action. Twit Text FOAVip Both cladribine and alemtuzumab may effect MS via B-cell depletion ????Neurol Neuroimmunol Neuroinflamm http://www.kidney.de/pget.php?&tw=1&pmid=28626781 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28626781 #FOAvip English Wikipedia <ref>{{Cite pmid|28626781}}</ref> Both cladribine and alemtuzumab may effect MS via B-cell depletion #MMPMID28626781 Baker D; Herrod SS; Alvarez-Gonzalez C; Zalewski L; Albor C; Schmierer K Neurol Neuroimmunol Neuroinflamm 2017[Jul]; 4 (4): ä PMID28626781show ga Objective:: To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies. Methods:: The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests. Data were extracted and statistically analyzed. Results:: Either dose of cladribine (3.5 mg/kg; 5.25 mg/kg) tested in CLARITY reduced the annualized relapse rate to 0.16?0.18 over 96 weeks, and both doses were similarly effective in reducing the risk of MRI lesions and disability. Surprisingly, however, T-cell depletion was rather modest. Cladribine 3.5 mg/kg depleted CD4+ cells by 40%?45% and CD8+ cells by 15%?30%, whereas alemtuzumab suppressed CD4+ cells by 70%?95% and CD8+ cells by 47%?55%. However, either dose of cladribine induced 70%?90% CD19+ B-cell depletion, similar to alemtuzumab (90%). CD19+ cells slowly repopulated to 15%?25% of baseline before cladribine redosing. However, alemtuzumab induced hyperrepopulation of CD19+ B cells 6?12 months after infusion, which probably forms the substrate for B-cell autoimmunities associated with alemtuzumab. Conclusions:: Cladribine induced only modest depletion of T cells, which may not be consistent with a marked influence on MS, based on previous CD4+ T-cell depletion studies. The therapeutic drug-response relationship with cladribine is more consistent with lasting B-cell depletion and, coupled with the success seen with monoclonal CD20+ depletion, suggests that B-cell suppression could be the major direct mechanism of action. äBoth cladribine and alemtuzumab may effect MS via B-cell depletion (epmc).pdf DeepDyve Pubget Overpricing