Treatment Exit in Aging Multiple Sclerosis: A Critical Review of Discontinuation, De-Escalation, and Dose Reduction, with Implications for GCC Practice
Year: 2026
Type: preprint
Abstract: Background: Aging and prolonged disease stability prompt reassessment of multiple sclerosis disease-modifying therapy. Discontinuation, switching, dose reduction and interval extension are distinct strategies. Stability during treatment may reflect reduced inflammatory activity, continuing drug effects, or both; chronological age alone cannot establish that withdrawal will preserve control. Objective: To critically assess treatment-exit evidence, reconcile apparently conflicting findings, distinguish treatment effects from prognostic associations, and examine implications for Gulf Cooperation Council (GCC) practice. Approach: A targeted, web-assisted critical narrative review examined accessible primary studies, corrections, conference reports, trial registrations and regional documents through 1 November 2026. Comparisons considered population, mechanism, strategy, outcome, surveillance, residual exposure, restart and alignment of follow-up. No meta-analysis, independent duplicate screening or formal certainty grading was performed. Principal findings: In DISCOMS, new disease activity occurred in 12.2% of discontinuers versus 4.7% of continuers over two years: an absolute difference of 7.5 percentage points (95% confidence interval, 0.6–15.0); non-inferiority was not established. DOT-MS stopped early after significant inflammatory activity in 8/45 discontinuers versus 0/44 continuers. Differences in eligibility, MRI thresholds and follow-up prevent attribution of these findings to age alone. Selected older-adult cohorts report limited relapse activity, but disability and patient-reported outcomes remain less certain. Natalizumab and fingolimod cessation carry early reactivation concerns requiring explicit consideration of the subsequent treatment pathway. Anti-CD20 cessation studies show sustained suppression in some selected populations, although residual exposure, treatment selection and imprecision limit conclusions about durable treatment independence. The included evidence does not establish a reliable comparative reduction in serious infection following treatment exit. Lower-efficacy switching can increase recurrence, while findings for specified extended intervals cannot be generalized to arbitrary dose reductions. Kuwait supplies direct natalizumab interval-extension evidence in younger adults; other GCC cohorts mainly inform treatment context. Regional guidance offers practical criteria that require appraisal against primary evidence and local monitoring conditions. Conclusions: Treatment reassessment should compare specified alternatives with continuation, communicate relevant absolute outcomes and uncertainty, and distinguish estimated benefit–harm from regional applicability. An author-proposed framework organizes patient goals, reasons for change, inflammatory activity, disability trajectory, exposure, harms, observation and reassessment. Its accompanying minimum dataset supports prospective evaluation without assigning a risk score or universal stopping threshold. Neither the framework’s feasibility nor its clinical utility has been validated. Mechanism-specific comparative studies and coordinated GCC research should evaluate inflammatory recurrence, disability, serious infections, treatment burden and continuity of care. Such evaluation should distinguish elective reassessment from treatment interruptions caused by changing access arrangements.
Source: Preprints.org
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225324496