Predictors of long-term interferon discontinuation in newly diagnosed relapsing multiple sclerosis

Background: Interferon-beta has long-term safety and efficacy profiles for Relapsing Remitting Multiple Sclerosis (RRMS). However, the increasing number of available treatments requires to improve patient profiling and to perform individualized clinical decisions. Therefore, the present study investigated predictors of Interferon-beta discontinuation. Methods: The present retrospective observational cohort study included 499 newly diagnosed, drug naive RRMS subjects receiving Interferon-beta as first disease modifying treatment (DMT), during a 7.9 +/- 3.8 year period, up to treatment discontinuation. Possible markers of interest were recorded at the time of diagnosis (age, gender, disease duration, baseline EDSS) or during follow-up as variables of disease evolution (relapse occurrence, annualized relapse rate -ARR-, 1-point EDSS progression, reaching of EDSS 4.0) or of treatment (high-dose Interferon-beta 1a, low-dose Interferon-beta 1a, or Interferon-beta 1b). Results: 217 patients (43.5%) discontinued the treatment during the follow-up period, with an incidence of 5% person-years (95%CI=4.6-5.9%). A multivariate Cox regression model showed an increased rate of Interferon-beta discontinuation for female gender (p=0.019; HR=1.428), higher baseline EDSS (p=0.026; HR=1.346), relapse occurrence (p=0.009; HR=1.618), higher ARR (p & $21t;0.001; HR=5.269), and Interferon-beta 1b treatment (p=0.019; HR=1.506); and a reduced rate for occurrence of EDSS progression (p & $2lt;0.001; HR=0.299). Conclusions: Most of the factors associated with Interferon-beta discontinuation are not modifiable, and are part of demographic features (i.e. gender), or of disease characteristics (i.e. disability at diagnosis), but should be taken into account when prescribing the first DMT for MS. Noteworthy, the use of Interferon-beta 1b is associated with 50% increased risk of discontinuation, compared with high-dose Interferon-beta 1a, highlighting the importance of drug formulations in treatment persistence.