Highlights from

EAN 2019

European Academy of Neurology

Oslo 29 June - 2 July 2019

Long-term effects of established treatments

Within the large armamentarium of MS treatments, it remains important to investigate long-term safety and efficacy of established options.


In the 2-year CARE-MS I trial, alemtuzumab improved clinical and MRI outcomes vs IFN-beta-1a in treatment-naïve relapsing-remitting MS patients. Safety remained consistent and manageable through year 8 in 2 consecutive extensions (TOPAZ). Efficacy was also maintained through year 8, with over half of patients (56%) receiving no additional treatment in the extension [1].

Six-year alemtuzumab efficacy and safety was reported in patients who were treated with IFN-beta-1a in CARE-MS I and switched to open-label alemtuzumab after two years [2]. This group showed improved efficacy outcomes, with a consistent safety profile. These improvements were maintained through year 6, with 67% receiving no additional treatment.


A post-hoc analysis was presented of efficacy and sustainability in patients with high disease activity who received cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) in the CLARITY study and placebo in the CLARITY extension study [3]. Clinical effect of cladribine was sustained in this subgroup of 98 patients. The annualised relapse rate (ARR) for qualifying relapses was 0.15. This was equal to or similar to the ARRs for all patients, independent of high disease activity status. Confirmed EDSS progression in the high disease activity subgroups was lower in the CLARITY extension study than in CLARITY.

Another poster analysed the rate and severity of relapse in CLARITY, with hospitalisation and steroid use as proxy indicators [4]. Relapse frequencies at week 96 in the CLARITY extension study were similar to those in CLARITY, and were notably lower than for the subgroup who switched to placebo in the extension study. Therefore, the efficacy of cladribine tablets demonstrated in CLARITY was sustained for each relapse type vs placebo in the CLARITY extension study without further treatment.


Teriflunomide’s effect on percentage of diffuse grey matter volume change (%GMVC) was found to be independent of its previously established effects on focal lesions and relapses among patients with a first clinical episode of MS shown in the phase 3 TOPIC study [5]. In the adjusted model, mean %GMVC after 2 years was −1.91% in the placebo (n=66) versus −1.10% in the 14 mg teriflunomide (n=87) groups (estimated treatment effect 0.80%; P=0.06). The estimated treatment effect of teriflunomide on %GMVC, independent of effects on lesions and relapses, was 100%.


The effect of long-term natalizumab treatment on metabolite biomarkers of neuronal and membrane integrity in lesional white matter (LWM) was assessed in relapsing-remitting MS patients [6]. At T0, myo-inositol ratios were significantly increased in LWM of natalizumab (n=8; P=0.019) and IFN/glatiramer acetate (n=10; P=0.022) patients compared with normal-appearing white matter of healthy controls (n=7). Over 48 months, myo-inositol ratios decreased significantly in the LWM in natalizumab vs IFN/glatiramer acetate patients (median change: -32%, P=0.033 vs -9%, P=0.084). The reduction in myo-inositol ratios in LWM of natalizumab-treated patients could reflect a decrease in gliotic activity, which may be related to natalizumab’s association with preservation of brain tissue integrity.

  1. Comi G, et al. EAN 2019, O1202.
  2. Montalban X, et al. EAN 2019, EPO2221.
  3. Vermersch P, et al. EAN 2019, EPO3211.
  4. Schippling S, et al. EAN 2019, EPO3196.
  5. Sprenger T, et al. EAN 2019, EPO3205.
  6. Schoonheim M, et al. EAN 2019, EPO3197.

Top image: @ iStockPhoto: koto_feja

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.