Contributions
Abstract: P1622
Type: LB Poster
Abstract Category: Late Breaking News
Background: Dimethyl fumarate (DMF) is an approved treatment for relapsing forms of multiple sclerosis (MS) that has been shown to cause a reduction in lymphocyte counts, exposing patients to a potential increased risk for progressive multifocal leukoencephalopathy (PML). This study aimed to examine the temporal profile of absolute and lymphocyte subset data from treatment start and relationships to clinical and radiological outcomes.
Methods: A retrospective review was performed on patients with an existing diagnosis of MS and history of DMF exposure from a single MS Center. Paraclinical tests results (white blood cell (WBC) count, absolute lymphocyte count (ALC), CD3, CD4, CD8, natural killer (NK), and CD19) and corresponding clinical relapse and MRI data were recorded. Data were acquired at baseline and in 3 to 4-month intervals post-treatment initiation extending to 3 years. Post-discontinuation data were collected monthly for up to 13 months. Mixed effect models were used to assess longitudinal correlations between cell counts and hazard ratios generated to determine the association between absolute lymphocyte counts and relapse.
Results: A total of 283 patients with confirmed relapsing-remitting MS (219 F; median age at DMF start date: 40.8 years, range: 16.1-66.7 years) were identified. Spearman"s rho tests indicated a significant correlation between absolute NK cells (p=0.005), CD4 (p=0.001), CD8 (p=0.001), and CD19 (p=0.001) counts at 6 months. Significant decreases in WBC and lymphocyte subset counts were appreciated between baseline and 9 months prior to plateauing. The time to a first new clinical or radiological event was extended when absolute lymphocyte counts were observed at 3 (Hazard Ratio (HR): 1.75, p=0.002) and 6 months (HR: 1.69, p=0.040). A longitudinal correlation between CD4 and CD19 counts at baseline and 9-months (p< 0.001) was also observed.
Interpretations: Absolute lymphocyte counts appear to be strongly associated with T and B-cell subset data. Reductions in absolute lymphocyte count values at months 3 and 6 post-treatment initiation appear to be associated with improved clinical and radiological outcomes. These data also assist in refining clinical surveillance recommendations for DMF and highlight the importance of diligent monitoring of lymphocyte counts within the first 9-months after drug initiation.
Disclosure:
Ms. Wright: nothing to disclose.
Ms. Winkler: nothing to disclose.
Mr. Newton: nothing to disclose.
Dr. M. P. Sormani received lecture fees from Teva, Merck Serono, Biogen, Novartis, and Genzyme and consulting fees from Merck Serono, Biogen, Teva, Genzyme, Roche, and Novartis.
Dr. D. T. Okuda received lecture fees from Acorda Therapeutics, Genzyme, and TEVA Neuroscience, consulting and advisory board fees from EMD Serono, Genentech, Genzyme, Novartis and TEVA Neuroscience, and research support from Biogen.
Abstract: P1622
Type: LB Poster
Abstract Category: Late Breaking News
Background: Dimethyl fumarate (DMF) is an approved treatment for relapsing forms of multiple sclerosis (MS) that has been shown to cause a reduction in lymphocyte counts, exposing patients to a potential increased risk for progressive multifocal leukoencephalopathy (PML). This study aimed to examine the temporal profile of absolute and lymphocyte subset data from treatment start and relationships to clinical and radiological outcomes.
Methods: A retrospective review was performed on patients with an existing diagnosis of MS and history of DMF exposure from a single MS Center. Paraclinical tests results (white blood cell (WBC) count, absolute lymphocyte count (ALC), CD3, CD4, CD8, natural killer (NK), and CD19) and corresponding clinical relapse and MRI data were recorded. Data were acquired at baseline and in 3 to 4-month intervals post-treatment initiation extending to 3 years. Post-discontinuation data were collected monthly for up to 13 months. Mixed effect models were used to assess longitudinal correlations between cell counts and hazard ratios generated to determine the association between absolute lymphocyte counts and relapse.
Results: A total of 283 patients with confirmed relapsing-remitting MS (219 F; median age at DMF start date: 40.8 years, range: 16.1-66.7 years) were identified. Spearman"s rho tests indicated a significant correlation between absolute NK cells (p=0.005), CD4 (p=0.001), CD8 (p=0.001), and CD19 (p=0.001) counts at 6 months. Significant decreases in WBC and lymphocyte subset counts were appreciated between baseline and 9 months prior to plateauing. The time to a first new clinical or radiological event was extended when absolute lymphocyte counts were observed at 3 (Hazard Ratio (HR): 1.75, p=0.002) and 6 months (HR: 1.69, p=0.040). A longitudinal correlation between CD4 and CD19 counts at baseline and 9-months (p< 0.001) was also observed.
Interpretations: Absolute lymphocyte counts appear to be strongly associated with T and B-cell subset data. Reductions in absolute lymphocyte count values at months 3 and 6 post-treatment initiation appear to be associated with improved clinical and radiological outcomes. These data also assist in refining clinical surveillance recommendations for DMF and highlight the importance of diligent monitoring of lymphocyte counts within the first 9-months after drug initiation.
Disclosure:
Ms. Wright: nothing to disclose.
Ms. Winkler: nothing to disclose.
Mr. Newton: nothing to disclose.
Dr. M. P. Sormani received lecture fees from Teva, Merck Serono, Biogen, Novartis, and Genzyme and consulting fees from Merck Serono, Biogen, Teva, Genzyme, Roche, and Novartis.
Dr. D. T. Okuda received lecture fees from Acorda Therapeutics, Genzyme, and TEVA Neuroscience, consulting and advisory board fees from EMD Serono, Genentech, Genzyme, Novartis and TEVA Neuroscience, and research support from Biogen.