Contributions
Abstract: EP1772
Type: ePoster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Objective: Examine the relationship between absolute lymphocyte count (ALC) and relapses in relapsing MS (RMS) patients on dimethyl fumarate (DMF).
Background: DEFINE and CONFIRM trials showed a 40-50% reduction in relapse rate in patients taking DMF 240mg twice a day, however about 1 in 4 patients had a relapse within two years. Grade III lymphopenia (ALC< 0.5x103 cells/µL) developed in 6% of patients in the clinical trials and 11% of DMF patients in our community hospital registry. A recent report showed a positive correlation between ALC and relapses for DMF patients. Here we analyzed data from the Providence DMF registry to determine if ALC at 6 months was correlated with relapse within the first year of treatment.
Methods: Patients prescribed DMF for RMS from March 2013 to March 2016 who had ALC values at 6 (±1) months and relapse data within one year of starting DMF were included. Poisson regression with the logarithm of time on DMF as an offset was used to analyze the relationship between ALC and annualized relapse rate (ARR). Cox proportional hazards regression was used to estimate the relationship between ALC and risk of relapse. Age, gender, and disease duration were included as covariates in the models. For both analyses, ALC was analyzed as a categorical variable with patients grouped into three ALC tertiles (lowest 33%, middle 33%, and highest 33%) and as a continuous variable.
Results: Of the 412 RMS patients in our registry during the study period, 116 patients met the inclusion criteria. Nineteen patients (16.4%) had a relapse within one year of starting DMF. While relapses increased with ALC tertiles (lowest tertile, ARR (SE)=0.07 (0.05), hazard ratio (HR)=reference; middle tertile, ARR (SE)=0.11 (0.07), HR=1.20; highest tertile, ARR (SE)=0.18 (0.10), HR=2.27), this trend was not significant (p=0.26 for ARR, p=0.128 for HR). With ALC as a continuous variable, there was suggestive but inconclusive evidence that higher ALC correlated with relapses (adjusted ARR ratio=1.06, p=0.086; adjusted HR=1.06, p=0.142 for every 0.1 x103 cells/µL increase).
Conclusion: Our results, although not statistically significant, suggest a potential relationship between higher ALC values and relapse. With a numerically larger cohort these differences may have reached statistical significance.
Disclosure:
K. Smoot - served as a consultant or speaker for Acorda, Biogen, EMD Serono, Genzyme, Genentech, Novartis and Teva; received research funding from Genentech.
K. Spinelli - Nothing to Disclose
L. Lucas - Nothing to Disclose
C. Chen - Nothing to Disclose
T. Stuchiner - Nothing to Disclose
E. Baraban - Nothing to Disclose
L. Gois - Nothing to Disclose
K. Kresa-Reahl - Honoraria from Biogen, Novartis, EMDSerono, TEVA, Genzyme. Consultant fees from Biogen, EMDserono, Genzyme, and Genentech. Research Support from Biogen, Novartis, EMDSerono, Genzyme, Mallinckrodt, and Genentech.
S. Cohan - Steering Committees and Advisory Boards for Biogen, Novartis, Sanofi Genzyme; Receives research support from Biogen, Novartis, Sanofi Genzyme, Roche Genentech, Mallingkrodt, MedDay; Speaking honoraria from Biogen, Acorda, Sanofi Genzyme, Novartis, Roche Genentech
Abstract: EP1772
Type: ePoster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Objective: Examine the relationship between absolute lymphocyte count (ALC) and relapses in relapsing MS (RMS) patients on dimethyl fumarate (DMF).
Background: DEFINE and CONFIRM trials showed a 40-50% reduction in relapse rate in patients taking DMF 240mg twice a day, however about 1 in 4 patients had a relapse within two years. Grade III lymphopenia (ALC< 0.5x103 cells/µL) developed in 6% of patients in the clinical trials and 11% of DMF patients in our community hospital registry. A recent report showed a positive correlation between ALC and relapses for DMF patients. Here we analyzed data from the Providence DMF registry to determine if ALC at 6 months was correlated with relapse within the first year of treatment.
Methods: Patients prescribed DMF for RMS from March 2013 to March 2016 who had ALC values at 6 (±1) months and relapse data within one year of starting DMF were included. Poisson regression with the logarithm of time on DMF as an offset was used to analyze the relationship between ALC and annualized relapse rate (ARR). Cox proportional hazards regression was used to estimate the relationship between ALC and risk of relapse. Age, gender, and disease duration were included as covariates in the models. For both analyses, ALC was analyzed as a categorical variable with patients grouped into three ALC tertiles (lowest 33%, middle 33%, and highest 33%) and as a continuous variable.
Results: Of the 412 RMS patients in our registry during the study period, 116 patients met the inclusion criteria. Nineteen patients (16.4%) had a relapse within one year of starting DMF. While relapses increased with ALC tertiles (lowest tertile, ARR (SE)=0.07 (0.05), hazard ratio (HR)=reference; middle tertile, ARR (SE)=0.11 (0.07), HR=1.20; highest tertile, ARR (SE)=0.18 (0.10), HR=2.27), this trend was not significant (p=0.26 for ARR, p=0.128 for HR). With ALC as a continuous variable, there was suggestive but inconclusive evidence that higher ALC correlated with relapses (adjusted ARR ratio=1.06, p=0.086; adjusted HR=1.06, p=0.142 for every 0.1 x103 cells/µL increase).
Conclusion: Our results, although not statistically significant, suggest a potential relationship between higher ALC values and relapse. With a numerically larger cohort these differences may have reached statistical significance.
Disclosure:
K. Smoot - served as a consultant or speaker for Acorda, Biogen, EMD Serono, Genzyme, Genentech, Novartis and Teva; received research funding from Genentech.
K. Spinelli - Nothing to Disclose
L. Lucas - Nothing to Disclose
C. Chen - Nothing to Disclose
T. Stuchiner - Nothing to Disclose
E. Baraban - Nothing to Disclose
L. Gois - Nothing to Disclose
K. Kresa-Reahl - Honoraria from Biogen, Novartis, EMDSerono, TEVA, Genzyme. Consultant fees from Biogen, EMDserono, Genzyme, and Genentech. Research Support from Biogen, Novartis, EMDSerono, Genzyme, Mallinckrodt, and Genentech.
S. Cohan - Steering Committees and Advisory Boards for Biogen, Novartis, Sanofi Genzyme; Receives research support from Biogen, Novartis, Sanofi Genzyme, Roche Genentech, Mallingkrodt, MedDay; Speaking honoraria from Biogen, Acorda, Sanofi Genzyme, Novartis, Roche Genentech