Abstract: P1174
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Cognitive impairment is common in multiple sclerosis (MS). The Symbol Digit Modalities Test (SDMT, oral or written) was used to assess cognitive impairment in PREFERMS, a prospective study of treatment retention with fingolimod 0.5 mg compared with injectable disease-modifying therapies (iDMTs) in patients with relapsing-remitting MS. Oral SDMT results showed a clinically meaningful improvement.
Objective: To better understand the relationship between oral SDMT results and clinical, cognitive and radiological outcomes in the study.
Methods: PREFERMS was a 12-month, phase 4, open-label, active-controlled, randomized, multicentre study. At enrolment, patients were either treatment-naïve or treated with one class of iDMT (interferon or glatiramer acetate). Patients were randomized (1:1) to fingolimod 0.5 mg or pre-selected iDMT. One on-study treatment switch was allowed after ≥3 months of treatment, or before if related to efficacy or safety. Cross-sectional, pairwise Pearson correlations of oral SDMT scores with clinical, physical disability measures, radiological and cognitive variables were calculated in the total study population. Correlations with oral SDMT score were examined at baseline, at the end of randomized treatment (EoRT) and at end of study (EoS).
Results: In PREFERMS, 875 patients were randomized (fingolimod, n=436; iDMT, n=439). Correlation coefficients (r) ranged from −0.52 to 0.55. Variables correlating most strongly with oral SDMT score at baseline were thalamic volume (r=0.43), Paced Auditory Serial Addition Test 3 (PASAT 3; r=0.47) and timed 25-foot walk (T25FW; r=−0.49), and at EoRT and at EoS, respectively, were PASAT 3 (r=0.55 and 0.50) and 9-hole peg test (9HPT; r=−0.52 and −0.48). Weaker correlations with oral SDMT score were seen at baseline with 9HPT (r=−0.38), T1 lesion volume (r=−0.37), T2 lesion volume (r=−0.36) and total brain volume (r=0.33), and at EoRT and EoS, respectively, with thalamic volume change (r=0.15 and 0.09) and T25FW (r=−0.38 and −0.35). Annualized relapse rate correlated weakly with oral SDMT scores at EoRT (r=−0.10) and EoS (r=−0.04), as did cortical grey-matter volume at each time point (baseline: r=0.16; EoRT, r=0.15; EoS, r=0.19).
Conclusions: In PREFERMS, cognitive function, measured by oral SDMT score, correlated strongly with thalamic volume at baseline and with other cognitive function measures (PASAT) and physical disability (T25FW, 9HPT) at various timepoints.
Disclosure: Douglas L Arnold has received honoraria from Bayer HealthCare, Biogen Idec, Coronado Biosciences, Eli Lilly, EMD Serono, Genentech, Genzyme, Novartis, Roche and Teva; has received research support from Bayer HealthCare and Biogen Idec; and is an employee of NeuroRx Research.
Ralph HB Benedict has received payment for consultation services from Biogen Idec, Genentech, Genzyme, research support from Acorda, Mallinckrodt, Genzyme, Novartis, Biogen, and the National Multiple Sclerosis Society, and provided speaking services for EMD Serono.
Bruce A C Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, Sanofi Genzyme, MedImmune, Novartis, Shire and Teva.
Xiangyi Meng, Lesley Schofield and Nadia Tenenbaum are employees of Novartis Pharmaceuticals Corporation.
Abstract: P1174
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Cognitive impairment is common in multiple sclerosis (MS). The Symbol Digit Modalities Test (SDMT, oral or written) was used to assess cognitive impairment in PREFERMS, a prospective study of treatment retention with fingolimod 0.5 mg compared with injectable disease-modifying therapies (iDMTs) in patients with relapsing-remitting MS. Oral SDMT results showed a clinically meaningful improvement.
Objective: To better understand the relationship between oral SDMT results and clinical, cognitive and radiological outcomes in the study.
Methods: PREFERMS was a 12-month, phase 4, open-label, active-controlled, randomized, multicentre study. At enrolment, patients were either treatment-naïve or treated with one class of iDMT (interferon or glatiramer acetate). Patients were randomized (1:1) to fingolimod 0.5 mg or pre-selected iDMT. One on-study treatment switch was allowed after ≥3 months of treatment, or before if related to efficacy or safety. Cross-sectional, pairwise Pearson correlations of oral SDMT scores with clinical, physical disability measures, radiological and cognitive variables were calculated in the total study population. Correlations with oral SDMT score were examined at baseline, at the end of randomized treatment (EoRT) and at end of study (EoS).
Results: In PREFERMS, 875 patients were randomized (fingolimod, n=436; iDMT, n=439). Correlation coefficients (r) ranged from −0.52 to 0.55. Variables correlating most strongly with oral SDMT score at baseline were thalamic volume (r=0.43), Paced Auditory Serial Addition Test 3 (PASAT 3; r=0.47) and timed 25-foot walk (T25FW; r=−0.49), and at EoRT and at EoS, respectively, were PASAT 3 (r=0.55 and 0.50) and 9-hole peg test (9HPT; r=−0.52 and −0.48). Weaker correlations with oral SDMT score were seen at baseline with 9HPT (r=−0.38), T1 lesion volume (r=−0.37), T2 lesion volume (r=−0.36) and total brain volume (r=0.33), and at EoRT and EoS, respectively, with thalamic volume change (r=0.15 and 0.09) and T25FW (r=−0.38 and −0.35). Annualized relapse rate correlated weakly with oral SDMT scores at EoRT (r=−0.10) and EoS (r=−0.04), as did cortical grey-matter volume at each time point (baseline: r=0.16; EoRT, r=0.15; EoS, r=0.19).
Conclusions: In PREFERMS, cognitive function, measured by oral SDMT score, correlated strongly with thalamic volume at baseline and with other cognitive function measures (PASAT) and physical disability (T25FW, 9HPT) at various timepoints.
Disclosure: Douglas L Arnold has received honoraria from Bayer HealthCare, Biogen Idec, Coronado Biosciences, Eli Lilly, EMD Serono, Genentech, Genzyme, Novartis, Roche and Teva; has received research support from Bayer HealthCare and Biogen Idec; and is an employee of NeuroRx Research.
Ralph HB Benedict has received payment for consultation services from Biogen Idec, Genentech, Genzyme, research support from Acorda, Mallinckrodt, Genzyme, Novartis, Biogen, and the National Multiple Sclerosis Society, and provided speaking services for EMD Serono.
Bruce A C Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, Sanofi Genzyme, MedImmune, Novartis, Shire and Teva.
Xiangyi Meng, Lesley Schofield and Nadia Tenenbaum are employees of Novartis Pharmaceuticals Corporation.