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

Interferon-β 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-β discontinuation.

The present retrospective observational cohort study included 499 newly diagnosed, drug naïve RRMS subjects receiving Interferon-β 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-β1a, low-dose Interferon-β1a, or Interferon-β1b).

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-β 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<0.001; HR=5.269), and Interferon-β1b treatment (p=0.019; HR=1.506); and a reduced rate for occurrence of EDSS progression (p<0.001; HR=0.299).

Most of the factors associated with Interferon-β 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-β1b is associated with 50% increased risk of discontinuation, compared with high-dose Interferon-β1a, highlighting the importance of drug formulations in treatment persistence.