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Predictors of relapse and disability progression in MS patients who discontinue disease-modifying therapy

      Highlights

      • 4842 patients in MSBase Registry stopped disease modifying therapy (DMT) for >6 months
      • During post-DMT period, the annualized relapse rate was 0.22 and confirmed disability (CDP) progression rate was 8.23 per 100 person-years
      • Younger and moderately disabled patients were at highest risk of post-DMT relapse
      • Patients who entered the progressive phase or were severely impaired at baseline were at highest risk for CDP during post-DMT follow up
      • Former natalizumab users had elevated relapse and CDP rates during follow up compared to other DMTs

      Abstract

      Background

      Discontinuation of disease-modifying therapies (DMTs) for MS is common. MSBase, a large global observational registry, affords a unique opportunity to investigate predictors of ‘post-DMT’ relapses and confirmed disability progression (CDP) in a diverse group of patients exposed to different DMTs.

      Materials/methods

      Main inclusion criteria: clinician-confirmed MS diagnosis (2010 McDonald criteria); age ≥ 18 at index DMT start; ≥12 months on index DMT prior to discontinuation; ≥24 months of follow-up post-discontinuation; did not restart DMT for ≥6 months. Predictors of time to first relapse and 3-month CDP were analyzed using Cox proportional hazards regression adjusted for age, gender, baseline EDSS, EDSS stability and relapse-free period for ≥1 year prior to discontinuation, calendar epoch, index DMT and reason for discontinuation.

      Results

      4842 patients (74.2% female) from 20 MSBase Centers met our inclusion criteria. 3556 (73%) discontinued one of IFNβ preparations, 849 (18%) - glatiramer acetate, 308 (6%) - natalizumab and 129 (3%) – fingolimod; other DMTs were excluded because too few records were available. Overall post-discontinuation annualized relapse rate (95% CI) was 0.224 (0.219, 0.229) and CDP rate was 8.23 (7.72, 8.76) per 100 person-years. Risk of post-DMT relapse was higher in younger patients, female patients, those with moderate disability and a relapse within 1 year of discontinuation. Hazard of CDP increased with increasing disability at baseline and disease progression within 3 years prior to stopping DMT. Of all the DMTs, only natalizumab was associated with increased risk of both post-DMT relapse and CDP.

      Conclusions

      Knowledge of post-DMT relapse and disability progression rates and predictors of post-DMT disease activity allows for a more informed discussion of DMT discontinuation in those patients who are considering this option.

      Keywords

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      1. Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)| PCORI.