Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis.

BACKGROUND

Focal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate the association of age and inflammatory disease activity.

METHODS

We used patient-level data from the AFFIRM (natalizumab vs placebo in relapsing-remitting MS, NCT00027300) and SENTINEL (natalizumab plus interferon beta vs interferon beta in relapsing remitting MS, NCT00030966) RCTs. We determined the proportion of participants developing new T2 lesions, contrast-enhancing lesions (CELs) and relapses over 2 years of follow-up as a function of age, and investigated the association of age with time to first relapse using time-to-event analyses.

RESULTS

At baseline, there were no differences between age groups in T2 lesion volume and number of relapses in the year before inclusion. In SENTINEL, older participants had a significantly lower number of CELs. During both trials, the number of new CELs and the proportion of participants developing new CELs were significantly lower in older age groups. The number of new T2 lesions and the proportion of participants with any radiological disease activity during follow-up were also lower in older age groups, especially in the control arms.

CONCLUSIONS

Older age is associated with a lower prevalence and degree of focal inflammatory disease activity in treated and untreated RRMS. Our findings inform the design of RCTs, and suggest that patient age should be taken into consideration when deciding on immunomodulatory treatment in RRMS.

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: EMS, EC, JC, JM and ZLEvK report no disclosures. JK received grants from Biogen, Novartis, TEVA, Bayer Schering Pharma, GlaxoSmithKline, Merck, Genzyme and Roche. PR received consulting and/or speaking honoraria from Alexion, Biogen, Celgene, Roche, Sanofi Genzyme, Viela and EMD Serono. JDB received honoraria from serving on the scientific advisory board and speaker’s bureau of Biogen, Celgene, EMD Serono, Genentech and Novartis. He has received research support from AbbVie, Alexion, Alkermes, Biogen, Celgene, Sanofi Genzyme, Genentech, Novartis and TG Therapeutics. GC served on data and safety monitoring boards: AstraZeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Horizon Pharmaceuticals, Hisun Pharmaceuticals, Mapi Pharmaceuticals, Merck, Merck/Pfizer, Opko Biologics, OncoImmune, Neurim, Novartis, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, VielaBio, Vivus, NHLBI (Protocol Review Committee), NICHD (OPRU oversight committee); consulting or advisory boards: Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein-Buendel Incorporated, Medimmune, Medday, Neurogenesis, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Roche, TG Therapeutics. GC is employed by the University of Alabama at Birmingham and President of Pythagoras, a private consulting company located in Birmingham, Alabama, USA. MK received consulting fees and travel support from Biogen, Novartis, Roche, Sanofi Genzyme and EMD Serono.