Contributions
Abstract: P663
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Objective: To assess real-world effectiveness and discontinuation of dimethyl fumarate (DMF) and fingolimod (FTY) over 24 months in patients with multiple sclerosis (MS) from two large academic centers.
Background: DMF and FTY are approved oral disease modifying therapies (DMTs) for relapsing MS. Previous randomized controlled trials (RCTs) and large observational studies, including our 12-month combined analysis, showed comparable efficacy at 12 and 24 months, but DMF patients were more likely to discontinue DMT earlier compared to FTY-treated patients. Observational studies are valuable when there are multiple available treatments and comparative RCTs are not feasible. Multi-site studies allow investigators to ascertain external validity of previously examined treatment effect differences.
Methods: Patients prescribed DMF (n = 737) and FTY (n = 535) from two large academic MS Centers (Cleveland Clinic and University of Colorado) with 24-month follow-up were identified. Discontinuation rates and measures of disease activity were assessed using propensity score (PS) weighting. Covariates used in the PS model included demographics and baseline clinical and MRI characteristics. Outcomes of interest included proportion of patients discontinuing DMT and proportion with disease activity [clinical relapse, gadolinium-enhancing (GdE) brain MRI lesions, and new T2 lesions]. Odds ratio estimates were calculated as DMF versus FTY.
Results: PS weighting showed excellent covariate balance. Our results showed discontinuation was more common in DMF (44.2%) compared to FTY (34.8%) over 24 months [OR=1.53, 95% CI (1.19, 1.96),
p< 0.001]. Leading cause for discontinuation was intolerability in both DMF (56.1% of all DMF discontinuations;) and FTY (46.2% of FTY discontinuations) [OR=1.67, 95% CI (1.22, 2.27), p=0.001]. Primary reason for discontinuation due to intolerability was GI side effects in DMF (57.9%) and headaches in FTY (14.0%). The percentage with relapses was low in both groups (DMF, 15.1%; FTY, 13.1%). There was no difference in the proportion with clinical relapses [OR=1.29, 95% CI (0.91, 1.82), p=0.15], GdE lesions [OR=1.44, 95% CI (0.94, 2.23), p=0.10], or new T2 lesions [OR=1.13, 95% CI (0.83, 1.55), p=0.43].
Conclusions: This combined analysis suggests similar effectiveness profiles for DMF and FTY in a large clinical population over 24 months. Discontinuation of both DMTs was common and occurred more frequently with DMF, largely driven by intolerability.
Disclosure:
Dr. Carrie Hersh has received speaking and consulting fees from Genzyme and TEVA; Grants- Genentech and Biogen Idec.
Miss Anasua Bandyopadhyay has nothing to disclose.
Dr. Samuel Cohn has nothing to disclose.
Ms. Claire Hara-Cleaver has received consulting fees from Biogen Idec, TEVA, EMD Serono, Acorda, Novartis, and Genzyme.
Dr. Robert Bermel has received consulting fees from Biogen Idec, Novartis, TEVA, Genzyme, Questcor; Grants/grants pending- Biogen Idec and Novartis.
Dr. Robert Fox has received consulting fees from Biogen Idec, MedDay, Novartis, Questcor, TEVA, and Xeonport; Grants-Novartis.
Dr. Jeffrey Cohen has received personal compensation for consulting for Adamas, Celgene, Mallinckrodt, Merck, and Novartis, and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
Dr. Daniel Ontaneda has received consulting fees from Biogen, Genentech, and Novartis. Grants- NIH, NMSS, Genzyme, Novartis, and Genentech.
Miss Brandi Vollmer has nothing to disclose.
Dr. Kavita Nair has received consulting fees from Astellas. Grants- Biogen, Novartis, and Genentech.
Dr. Stefan Sillau has nothing to disclose.
Dr. John Corboy has received honoraria from Prime CME, serves as a board member with the NMSS, and serves as an editor for Neurology: Clinical Practice. Grants/Research Support- Med Day, Novartis, Biogen, PCORI, and NMSS.
Dr. Timothy Vollmer has received compensation for activities such as advisory boards, lectures and consultancy with the following companies and organizations: Abbvie Inc, Alcimed, American Academy of Neurology, CB Partners, Capmaels and Rasford, Celestial Intas Pharmaceuticals LTD, Compass Learning, Genentech/Roche, Genzyme/Sanofi, Goodwin Procter LLP, IMS Consulting Group, Medscape, Novartis Pharmaceuticals, Oxford Pharmagenesis, Patient Centered Outcomes Research Institute, Sommer Consulting, and Teva Neuroscience. Research support- Genzyme, Teva Neuroscience, NIH/NINDS, Rocky Mountain MS Center, EMD Serono, Biogen Idec, Ono Pharmaceuticals, MedImmune, Genetech/Roche, and TG Therapeutics Inc.
Dr. Enrique Alvarez has received consulting fees from Biogen, Genzyme, Genentech, Novartis, and TG Pharmaceuticals. Grants- Acorda, Biogen, Genentech, Novartis, and Rocky Mountain MS Center.
Abstract: P663
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Objective: To assess real-world effectiveness and discontinuation of dimethyl fumarate (DMF) and fingolimod (FTY) over 24 months in patients with multiple sclerosis (MS) from two large academic centers.
Background: DMF and FTY are approved oral disease modifying therapies (DMTs) for relapsing MS. Previous randomized controlled trials (RCTs) and large observational studies, including our 12-month combined analysis, showed comparable efficacy at 12 and 24 months, but DMF patients were more likely to discontinue DMT earlier compared to FTY-treated patients. Observational studies are valuable when there are multiple available treatments and comparative RCTs are not feasible. Multi-site studies allow investigators to ascertain external validity of previously examined treatment effect differences.
Methods: Patients prescribed DMF (n = 737) and FTY (n = 535) from two large academic MS Centers (Cleveland Clinic and University of Colorado) with 24-month follow-up were identified. Discontinuation rates and measures of disease activity were assessed using propensity score (PS) weighting. Covariates used in the PS model included demographics and baseline clinical and MRI characteristics. Outcomes of interest included proportion of patients discontinuing DMT and proportion with disease activity [clinical relapse, gadolinium-enhancing (GdE) brain MRI lesions, and new T2 lesions]. Odds ratio estimates were calculated as DMF versus FTY.
Results: PS weighting showed excellent covariate balance. Our results showed discontinuation was more common in DMF (44.2%) compared to FTY (34.8%) over 24 months [OR=1.53, 95% CI (1.19, 1.96),
p< 0.001]. Leading cause for discontinuation was intolerability in both DMF (56.1% of all DMF discontinuations;) and FTY (46.2% of FTY discontinuations) [OR=1.67, 95% CI (1.22, 2.27), p=0.001]. Primary reason for discontinuation due to intolerability was GI side effects in DMF (57.9%) and headaches in FTY (14.0%). The percentage with relapses was low in both groups (DMF, 15.1%; FTY, 13.1%). There was no difference in the proportion with clinical relapses [OR=1.29, 95% CI (0.91, 1.82), p=0.15], GdE lesions [OR=1.44, 95% CI (0.94, 2.23), p=0.10], or new T2 lesions [OR=1.13, 95% CI (0.83, 1.55), p=0.43].
Conclusions: This combined analysis suggests similar effectiveness profiles for DMF and FTY in a large clinical population over 24 months. Discontinuation of both DMTs was common and occurred more frequently with DMF, largely driven by intolerability.
Disclosure:
Dr. Carrie Hersh has received speaking and consulting fees from Genzyme and TEVA; Grants- Genentech and Biogen Idec.
Miss Anasua Bandyopadhyay has nothing to disclose.
Dr. Samuel Cohn has nothing to disclose.
Ms. Claire Hara-Cleaver has received consulting fees from Biogen Idec, TEVA, EMD Serono, Acorda, Novartis, and Genzyme.
Dr. Robert Bermel has received consulting fees from Biogen Idec, Novartis, TEVA, Genzyme, Questcor; Grants/grants pending- Biogen Idec and Novartis.
Dr. Robert Fox has received consulting fees from Biogen Idec, MedDay, Novartis, Questcor, TEVA, and Xeonport; Grants-Novartis.
Dr. Jeffrey Cohen has received personal compensation for consulting for Adamas, Celgene, Mallinckrodt, Merck, and Novartis, and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
Dr. Daniel Ontaneda has received consulting fees from Biogen, Genentech, and Novartis. Grants- NIH, NMSS, Genzyme, Novartis, and Genentech.
Miss Brandi Vollmer has nothing to disclose.
Dr. Kavita Nair has received consulting fees from Astellas. Grants- Biogen, Novartis, and Genentech.
Dr. Stefan Sillau has nothing to disclose.
Dr. John Corboy has received honoraria from Prime CME, serves as a board member with the NMSS, and serves as an editor for Neurology: Clinical Practice. Grants/Research Support- Med Day, Novartis, Biogen, PCORI, and NMSS.
Dr. Timothy Vollmer has received compensation for activities such as advisory boards, lectures and consultancy with the following companies and organizations: Abbvie Inc, Alcimed, American Academy of Neurology, CB Partners, Capmaels and Rasford, Celestial Intas Pharmaceuticals LTD, Compass Learning, Genentech/Roche, Genzyme/Sanofi, Goodwin Procter LLP, IMS Consulting Group, Medscape, Novartis Pharmaceuticals, Oxford Pharmagenesis, Patient Centered Outcomes Research Institute, Sommer Consulting, and Teva Neuroscience. Research support- Genzyme, Teva Neuroscience, NIH/NINDS, Rocky Mountain MS Center, EMD Serono, Biogen Idec, Ono Pharmaceuticals, MedImmune, Genetech/Roche, and TG Therapeutics Inc.
Dr. Enrique Alvarez has received consulting fees from Biogen, Genzyme, Genentech, Novartis, and TG Pharmaceuticals. Grants- Acorda, Biogen, Genentech, Novartis, and Rocky Mountain MS Center.