Contributions
Abstract: P724
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Oral multiple sclerosis (MS) medications, dimethyl fumarate (DMF) and fingolimod (FG) are associated with decreased absolute lymphocyte count (ALC). Lymphopenia is linked to increased risk of infections including few cases of progressive multifocal leukoencephalopathy (PML) in patients treated with these drugs. There is currently no guideline to identify patients at risk.
Objective: To investigate the frequency of lymphopenia and its predictors in patients treated with DMF or FG.
Methods: Eligible subjects from the Partners MS Center database were identified (DMF=405, FG=300). Univariate and multivariate analyses were performed via a logistic regression model to assess the association between patients" demographics, baseline ALC, body mass index, vitamin D level and binary outcomes of lymphopenia grades. ALC grading defined as; grade 2 (500-800/mm3), grade 3 (200-500/mm3), grade 3b (< 350/mm3) and grade 4 (< 200/mm3). Leukopenia grading defined as; grade2 (WBC: 2000-3000/mm3) and grade 3 (WBC: 1000-2000/mm3).
Results: In DMF group, the incidence of lymphopenia grade 2 and 2/3-3 within 3 years after treatment initiation was 17%; CI=(13%, 21%) and 11%; CI=(8%, 14%). Lower baseline ALC were associated with higher odds of lymphopenia grade 2 and grade 2/3-3 (p=0.0046, p=0.0021). In grade 2, older age was associated with higher odds of lymphopenia (p=0.0211). When age was stratified into the < 30 (OR=0.2, p=0.0298), 30-50 (OR=0.5, p=0.0085) and >50 years categories, younger patients were at a significantly lower risk of developing lymphopenia, as compared to >50 years. In FG group, lymphopenia grade 4 and grade 3b/4 were present in 17%; CI=(13%, 21%) and 59%; CI=(53%, 64%) within 5 years after treatment initiation. The odds of developing lymphopenia grade 4 and grade 3b/4 were significantly higher in female patients (p= 0.011 and p= 0.002). Prior treatment with natalizumab was associated with an increased odds of lymphopenia grade 4 (p= 0.012), while no previous treatment was associated with a lower odds of lymphopenia grade 3b/4 (p=0.03). Furthermore, patients without previous MS treatment and longer disease duration were at higher risk for leukopenia grade 2/3(p= 0.025 and p= 0.012).
Conclusion: Older age, and lower baseline ALC were associated with lymphopenia with DMF use, while being a female and prior MS treatment are important determinant of lymphopenia with FG use. These factors can be used to develop risk stratification guidelines.
Disclosure:
M.Baharnoori: nothing to disclose. A.Chua: has received support from Verily Life Sciences.
C. Diaz-Cruz: has received research support from Merck Serono.
B. Healy: received grant support from Novartis, Merck Serono, Genzyme and Verily Life Sciences. I am also on the Biogen Idec Worldwide Medical Biostatistics MS Advisory Board.
James Stankiewicz: has received personal compensation for consulting with Hoffman-LaRoche, Biogen, Novartis, Bayer, EMD Serono, Genzyme, Teva neuroscience.
Howard Weiner: has received personal compensation for consulting, speaking activities and has served on the scientific advisory board of companies including Biogen Idec, Novartis, EMD Serono, Teva.
T. Chitnis: received personal compensation for advisory boards/consulting for Hoffman-La Roche, Biogen and Novartis Pharmaceuticals and financial support for research activities from Biogen, Merck Serono and Novartis Pharmaceuticals
Abstract: P724
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Oral multiple sclerosis (MS) medications, dimethyl fumarate (DMF) and fingolimod (FG) are associated with decreased absolute lymphocyte count (ALC). Lymphopenia is linked to increased risk of infections including few cases of progressive multifocal leukoencephalopathy (PML) in patients treated with these drugs. There is currently no guideline to identify patients at risk.
Objective: To investigate the frequency of lymphopenia and its predictors in patients treated with DMF or FG.
Methods: Eligible subjects from the Partners MS Center database were identified (DMF=405, FG=300). Univariate and multivariate analyses were performed via a logistic regression model to assess the association between patients" demographics, baseline ALC, body mass index, vitamin D level and binary outcomes of lymphopenia grades. ALC grading defined as; grade 2 (500-800/mm3), grade 3 (200-500/mm3), grade 3b (< 350/mm3) and grade 4 (< 200/mm3). Leukopenia grading defined as; grade2 (WBC: 2000-3000/mm3) and grade 3 (WBC: 1000-2000/mm3).
Results: In DMF group, the incidence of lymphopenia grade 2 and 2/3-3 within 3 years after treatment initiation was 17%; CI=(13%, 21%) and 11%; CI=(8%, 14%). Lower baseline ALC were associated with higher odds of lymphopenia grade 2 and grade 2/3-3 (p=0.0046, p=0.0021). In grade 2, older age was associated with higher odds of lymphopenia (p=0.0211). When age was stratified into the < 30 (OR=0.2, p=0.0298), 30-50 (OR=0.5, p=0.0085) and >50 years categories, younger patients were at a significantly lower risk of developing lymphopenia, as compared to >50 years. In FG group, lymphopenia grade 4 and grade 3b/4 were present in 17%; CI=(13%, 21%) and 59%; CI=(53%, 64%) within 5 years after treatment initiation. The odds of developing lymphopenia grade 4 and grade 3b/4 were significantly higher in female patients (p= 0.011 and p= 0.002). Prior treatment with natalizumab was associated with an increased odds of lymphopenia grade 4 (p= 0.012), while no previous treatment was associated with a lower odds of lymphopenia grade 3b/4 (p=0.03). Furthermore, patients without previous MS treatment and longer disease duration were at higher risk for leukopenia grade 2/3(p= 0.025 and p= 0.012).
Conclusion: Older age, and lower baseline ALC were associated with lymphopenia with DMF use, while being a female and prior MS treatment are important determinant of lymphopenia with FG use. These factors can be used to develop risk stratification guidelines.
Disclosure:
M.Baharnoori: nothing to disclose. A.Chua: has received support from Verily Life Sciences.
C. Diaz-Cruz: has received research support from Merck Serono.
B. Healy: received grant support from Novartis, Merck Serono, Genzyme and Verily Life Sciences. I am also on the Biogen Idec Worldwide Medical Biostatistics MS Advisory Board.
James Stankiewicz: has received personal compensation for consulting with Hoffman-LaRoche, Biogen, Novartis, Bayer, EMD Serono, Genzyme, Teva neuroscience.
Howard Weiner: has received personal compensation for consulting, speaking activities and has served on the scientific advisory board of companies including Biogen Idec, Novartis, EMD Serono, Teva.
T. Chitnis: received personal compensation for advisory boards/consulting for Hoffman-La Roche, Biogen and Novartis Pharmaceuticals and financial support for research activities from Biogen, Merck Serono and Novartis Pharmaceuticals