Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials.

Background

Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing-remitting MS (RRMS).

Methods

DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level.

Results

Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo.

Conclusion

DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age.

Informations de copyright

© The Author(s), 2020.

Déclaration de conflit d'intérêts

Conflict of interest statement: YZ, NGC, ASa, WC, MW, PK, BB declare no competing interests related to this study. ASh is currently funded through a Clinician Scientist Development Award by the National Multiple Sclerosis Society and a Physician Scientist Training Program Award by the University of Nebraska Medical Center. GC has participated on data-monitoring and safety-monitoring boards for Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, CSL Behring, Galmed Pharmaceuticals, Horizon Pharmaceuticals, Hisun Pharmaceuticals, Mapi Pharmaceuticals, Merck, Merck/Pfizer, Opko Biologics, Neurim, Novartis, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva pharmaceuticals, Vivus, NHLBI (Protocol Review Committee), NICHD (OPRU oversight committee); participated in consulting or advisory boards for Biogen, Click Therapeutics, Genzyme, Genentech, Gilgamesh Pharmaceuticals, GW Pharmaceuticals, Klein-Buendel Incorporated, Medimmune, Medday, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion Pharmaceuticals, Roche, Somahlution, TG Therapeutics; is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc., a private consulting company located in Birmingham AL. FL has participated in consulting agreements/advisory boards/DSMB for Biogen; EMD Serono; Novartis; Teva; Actelion; Sanofi/Genzyme; Acorda; Roche/Genentech; MedImmune/ Viela Bio; Receptos/Celgene; TG Therapeutics; Medday; Atara Biotherapeutics; Polpharma; Mapi Pharma; Innate Immunotherapeutics; Apitope; Orion Biotechnology; Brainstorm Cell Therapeutics; Jazz Pharmaceuticals; GW Pharma; Mylan; Immunic; Population Council. OS serves on the editorial boards of Therapeutic Advances in Neurological Disorders and on data monitoring committees for Genentech-Roche, Pfizer, and TG Therapeutics without monetary compensation, advised EMD Serono, Celgene, Genentech, TG Therapeutics, and Genzyme, and receives grant support from Sanofi Genzyme and EMD Serono.