Contributions
Abstract: P717
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Dimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease modifying therapies (DMTs) for treatment of relapsing multiple sclerosis (MS). Both reduce circulating absolute lymphocyte counts (ALC), though the mechanism and significance differ. Current prescribing information recommends obtaining ALC before initiating treatment and during routine surveillance.
Objective: To describe absolute lymphopenia in DMF and FTY in clinical practice.
Design and methods: We identified 458 DMF and 317 FTY patients in a large academic MS center. ALC were evaluated at baseline and 12 months with data available for 360 DMF (78.6%) and 244 FTY (77.0%) patients. Unadjusted comparative data were analyzed via descriptive and chi-square statistical methods, and adjusted ALC comparisons were made via propensity score weighting.
Results: Baseline mean ALC were DMF 1.94 and FTY 2.12. At 12 months 269 (74.7%) DMF patients had ALC within normal range defined as ALC ≥1.0 x 109/L compared to 34 (13.9%) FTY patients. For DMF mean ALC decreased by 30% to 1.48 at 12 months, compared to a decrease of 82% to 0.63 with FTY. With DMF grade 1 lymphopenia (< 1.0-≥0.8) was found in 5.8%; grade 2 (< 0.8-≥0.5) in 13.8%; and grade 3 (< 0.5-≥0.2) in 5.6%. No DMF patients developed grade 4 lymphopenia (< 0.2). Nineteen DMF patients discontinued treatment due to lymphopenia (grade 1 n = 9; grade 2-3 n = 10), though there were no associated infections. In FTY patients grade 1 lymphopenia developed in 1.6%; grade 2-3 in 81.1%; and grade 4 in 3.3%. Three patients discontinued FTY due to grade 4 lymphopenia, one of which was associated with moderately severe upper respiratory tract infection. Both unadjusted [difference= 0.85, 95% CI (0.72, 0.98)] and adjusted [difference= 0.80, 95% CI (0.65, 0.96)] comparisons showed higher mean ALC with DMF versus FTY at 12 months. There were no cases of fungal infection or PML with either DMT.
Conclusion: Over one year, mean ALC decline in DMF and FTY patients in clinical practice was comparable to that reported in phase 3 clinical trials. As expected, absolute lymphopenia is less frequent with DMF compared to FTY, though the level of ALC reduction that is clinically concerning is different for the two DMTs. In our cohort clinical concern regarding lymphopenia led to more frequent discontinuation of DMF compared to FTY.
Disclosure:
Dr. Carrie Hersh is supported by National Multiple Sclerosis Society Sylvia Lawry Physician Fellowship Award.
Dr. Samuel Cohn - there is no conflict of interest.
Ms. Claire Hara-Cleaver has received consulting or speaking fees from Biogen Idec, TEVA, EMD Serono, Acorda, Novartis, and Genzyme.
Dr. Robert Bermel has received consulting or speaking fees from Biogen Idec, Novartis, TEVA, Genzyme, and Questcor.
Dr. Robert Fox has received consulting fees from Biogen Idec, MedDay, Novartis, Questcor, TEVA, and Xeonport.
Dr. Jeffrey Cohen has received consulting fees from Biogen Idec, EMD Serono, Genzyme, Novartis, Receptos, Synthon, TEVA, and Vaccinex.
Dr. Daniel Ontaneda is supported by KL2 TR000440/TR/NCATS NIH Grant.
Abstract: P717
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Dimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease modifying therapies (DMTs) for treatment of relapsing multiple sclerosis (MS). Both reduce circulating absolute lymphocyte counts (ALC), though the mechanism and significance differ. Current prescribing information recommends obtaining ALC before initiating treatment and during routine surveillance.
Objective: To describe absolute lymphopenia in DMF and FTY in clinical practice.
Design and methods: We identified 458 DMF and 317 FTY patients in a large academic MS center. ALC were evaluated at baseline and 12 months with data available for 360 DMF (78.6%) and 244 FTY (77.0%) patients. Unadjusted comparative data were analyzed via descriptive and chi-square statistical methods, and adjusted ALC comparisons were made via propensity score weighting.
Results: Baseline mean ALC were DMF 1.94 and FTY 2.12. At 12 months 269 (74.7%) DMF patients had ALC within normal range defined as ALC ≥1.0 x 109/L compared to 34 (13.9%) FTY patients. For DMF mean ALC decreased by 30% to 1.48 at 12 months, compared to a decrease of 82% to 0.63 with FTY. With DMF grade 1 lymphopenia (< 1.0-≥0.8) was found in 5.8%; grade 2 (< 0.8-≥0.5) in 13.8%; and grade 3 (< 0.5-≥0.2) in 5.6%. No DMF patients developed grade 4 lymphopenia (< 0.2). Nineteen DMF patients discontinued treatment due to lymphopenia (grade 1 n = 9; grade 2-3 n = 10), though there were no associated infections. In FTY patients grade 1 lymphopenia developed in 1.6%; grade 2-3 in 81.1%; and grade 4 in 3.3%. Three patients discontinued FTY due to grade 4 lymphopenia, one of which was associated with moderately severe upper respiratory tract infection. Both unadjusted [difference= 0.85, 95% CI (0.72, 0.98)] and adjusted [difference= 0.80, 95% CI (0.65, 0.96)] comparisons showed higher mean ALC with DMF versus FTY at 12 months. There were no cases of fungal infection or PML with either DMT.
Conclusion: Over one year, mean ALC decline in DMF and FTY patients in clinical practice was comparable to that reported in phase 3 clinical trials. As expected, absolute lymphopenia is less frequent with DMF compared to FTY, though the level of ALC reduction that is clinically concerning is different for the two DMTs. In our cohort clinical concern regarding lymphopenia led to more frequent discontinuation of DMF compared to FTY.
Disclosure:
Dr. Carrie Hersh is supported by National Multiple Sclerosis Society Sylvia Lawry Physician Fellowship Award.
Dr. Samuel Cohn - there is no conflict of interest.
Ms. Claire Hara-Cleaver has received consulting or speaking fees from Biogen Idec, TEVA, EMD Serono, Acorda, Novartis, and Genzyme.
Dr. Robert Bermel has received consulting or speaking fees from Biogen Idec, Novartis, TEVA, Genzyme, and Questcor.
Dr. Robert Fox has received consulting fees from Biogen Idec, MedDay, Novartis, Questcor, TEVA, and Xeonport.
Dr. Jeffrey Cohen has received consulting fees from Biogen Idec, EMD Serono, Genzyme, Novartis, Receptos, Synthon, TEVA, and Vaccinex.
Dr. Daniel Ontaneda is supported by KL2 TR000440/TR/NCATS NIH Grant.