Dimethyl fumarate vs. glatiramer acetate: In the real-world EFFECT study (n=1890), the proportion of patients relapse-free at 1 year was higher with DMF vs. GA (89% vs. 80%) (Chan et al. ECTRIMS 2017; abstract P1160). The adjusted ARR ratio was one-third lower with DMF (0.66).
Fingolimod vs. dimethyl fumarate (three analyses): Seven MS clinics in Italy reported on 895 patients on fingolimod or DMF (Prosperini et al. ECTRIMS 2017; abstract P665). The DMF group had less active disease at baseline. The two drugs were similarly effective in de novo patients, but there was a trend to superior efficacy with fingolimod in previously-treated patients (hazard ratio 0.62). An analysis of the German NeuroTransData registry reported that the two drugs were comparable, but time to discontinuation was significantly longer with fingolimod (Braune et al. ECTRIMS 2017; abstract P651). Similarly, a single-centre analysis found that clinical efficacy was equivalent, but the discontinuation rate at 24 months was lower with fingolimod vs. DMF (34.8% vs. 44.2%), primarily because of better tolerability (Hersh et al. ECTRIMS 2017; abstract P663 and P680).
Fingolimod vs. teriflunomide or DMF: MSBase data for 2985 RRMS patients on treatment for at least 6 months were examined (Kalincik et al. ECTRIMS 2017; abstract P677). ARR was lowest with DMF compared to teriflunomide (0.17 vs. 0.26); ARR with DMF and fingolimod was comparable (0.21 vs. 0.24). Fingolimod was associated with the lowest rate of discontinuation; discontinuation rates were similar for teriflunomide and DMF.
Fingolimod vs. the world: MSBase examined the persistence rates with fingolimod compared to all other DMTs (Spelman et al. ECTRIMS 2017; abstract P1193). The persistence rate was highest with fingolimod (median 24 months) and natalizumab (18 months). Patients were significantly more likely to remain on fingolimod compared to all other DMTs. Discontinuations were three-fold more likely with IFNbeta-1a IM, and twice as likely with DMF compared to fingolimod.
Cladribine vs. Others: An MSBase propensity-matched analysis reported that the probability of remaining relapse-free was significantly higher with cladribine vs. IFN-beta, similar for cladribine vs. fingolimod, and poorer with cladribine vs. natalizumab (Kalincik et al. ECTRIMS 2017; abstract P1138). Cladribine was superior to IFN-beta and similar to fingolimod with respect to the proportion free of disability progression, and was superior to all comparators with respect to proportion of patients with clinical disability improvement. The authors concluded that cladribine could be associated with superior recovery from disability compared to IFN-beta, fingolimod and natalizumab.
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Natalizumab to fingolimod or alemtuzumab: One retrospective analysis examined data for patients who switched from natalizumab because of PML concerns or lack of efficacy (Pfeuffer et al. ECTRIMS 2017; abstract P689). Alemtuzumab was superior to fingolimod with respect to relapse frequency, risk of disability progression and rate of drug discontinuation over the initial 12-month period after switching. One-third of fingolimod-treated patients experienced a relapse compared to 10% of those on alemtuzumab.
Natalizumab to alemtuzumab: The retrospective ANSWERS-MS study in the UK/Ireland collected data for all patients switched from natalizumab to alemtuzumab due to lack of efficacy, PML risk or hypersensitivity reactions (n=77) (Gallagher et al. ECTRIMS 2017; abstract P726). In the interim analysis of 37 patients, two-thirds received two courses of alemtuzumab; the mean washout period was 136 days. A total of 89.2% of alemtuzumab-treated patients have required not further treatment. Six patients (16.2%) developed autoimmune thyroid disease, and five patients (13.5%) developed significant infections.
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New analyses of DMT effectiveness
Three studies presented at ECTRIMS 2017 addressed whether patient outcomes have improved in the DMT era. An analysis of the Swedish MS registry for the period 1995-2010 found a 3% decrease per year in the risk of confirmed EDSS 3.0, a 6% decrease per year for risk of EDSS 4.0, and a 7% decrease per year for risk of EDSS 6.0 for patients with RRMS (Beiki et al. ECTRIMS 2017; abstract 215). There was no gain in reaching EDSS milestones in patients with progressive-onset MS.
An MS centre in Italy retrospectively examined data for all MS patients for the period 1980-2015 (n=1370) (Cordioli et al. ECTRIMS 2017; abstract 197). The average age at diagnosis increased in recent years, from 32 years to 35 years. Average age of reaching EDSS 6.0 was older in more recent cohorts. Compared to 1990 as the reference year, the probability of reaching EDSS 6.0 was reduced 17% for patients diagnosed in 1996-2000, by 38% for those diagnosed in 2006-2010, and by 75% for those diagnosed in 2011-2015. For patients diagnosed before the year 2000, 29% reached EDSS 6.0 by age 50 years, compared to 10% of those diagnosed after the year 2000.
The MSBase group examined whether DMTs have delayed conversion to SPMS (Brown et al. ECTRIMS 2017; abstract 128). A total of 486 patients treated for at least 4 years with one DMT (injectable, fingolimod, natalizumab or alemtuzumab) were propensity matched to 622 untreated patients from an historical cohort. The median duration of follow-up was 7.9 years on injectables, 4.6 years on fingolimod, 4.9 years for natalizumab, and 7.2 years for alemtuzumab. All treatments reduced the risk of SPMS compared to untreated controls. High-efficacy therapies (natalizumab and alemtuzumab) were significantly more effective than injectables in delaying conversion to SPMS (hazard ratio 0.65), suggesting that there is a modifiable inflammatory component contributing to SPMS, at least in the early stages.
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Use of gadolinium – consensus statement
A North American group has developed a consensus statement on the use of gadolinium for MRIs used in MS diagnosis and follow-up (Traboulsee et al. ECTRIMS 2017; abstract P780). The group stated that gadolinium is essential to the diagnostic evaluation of patients with suspected MS. During routine follow-up, use of gadolinium may be useful to guide treatment decisions in patients with suspected ongoing disease activity, to confirm a lack of disease activity, and to facilitate DMT selection. However, the group noted that the usefulness of gadolinium in demonstrating inflammatory activity must be balanced against concerns about potential safety concerns. Gadolinium contrast agents have been associated with nephrogenic systemic fibrosis in patients with kidney disease. Repeated gadolinium exposure may also lead to accumulation in the brain and other tissues, to unknown effect.
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Pregnancy rate on the increase in women with MS
An analysis of the MSBase registry found that incidence of pregnancy has increased for the period 2011-2016 compared to 2005-2010 (Jokubaitis et al. ECTRIMS 2017; abstract P353). The analysis included all women of childbearing age (ages 15-45 years) with relapse-onset MS (n=9098).
A total of 1,178 women (12.9%) recorded 1,521 pregnancies during the study period. The annualized incidence rate of pregnancy increased from 0.040 in 2005-2010, to 0.044 in 2011-2016. Incidence rates were highest in women aged 25-35 years (0.07), and lowest in women aged 40-45 years (0.006).
The proportion of pregnancies that occurred while on a DMT increased from 26.5% in 2006, to 61.7% in 2016 (average 41.7% for the entire study period). Pregnancies occurred more frequently during treatment with IFN-beta (55.0% of pregnancies), glatiramer acetate (21.7%), and natalizumab (16.4%), and less commonly on oral therapies (6%). The median duration of DMT exposure during pregnancy was 30 days. The authors noted that the higher pregnancy rate may be the result of closer monitoring due to the increasing use of DMTs with teratogenic potential, rather than an increase in the rate of pregnancy.
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