Current DMTs – an overview of observational studies


REPORT FROM ECTRIMS – BARCELONA, SPAIN – OCTOBER 7-10, 2015 – The following is a summary of real-world studies of current DMT use in clinical practice.

Interferon-beta-1a s.c.: The Centre hospitalier de l’Université de Montréal (CHUM) surveyed 296 MS patients on IFNbeta-1a for at least two years and untreated patients about cognition, quality of life and employment (Rouleau et al. ECTRIMS 2015; abstract P313). QoL was assessed with the MSQoL-54; cognition was evaluated with MACFIMS. Mean disease duration was 15 years for the IFNbeta group and 21 years for the untreated patients. No significant differences were seen between the two groups with respect to mean EDSS score (2.0), proportion with cognitive impairment (treated 26%, untreated 32%), or work status. The authors noted that the low level of cognitive impairment was likely to be the reason that patients were able to continue working.

Teriflunomide: CHUM also analysed data for 289 patients treated with teriflunomide at two Montreal MS centres (CHUM, Neuro Rive-Sud) for a maximum of 17 months (Duquette et al. ECTRIMS 2015; abstract P541). A majority of patients had received prior therapy. During the observation period, 10% of patients experienced one or two relapses. There was no evidence of rebound disease activity when switching from a DMT to teriflunomide. A total of 11% discontinued teriflunomide; reasons for discontinuation were poor tolerability (63%), lack of efficacy (22%), adverse events (12%), and planned pregnancy (3%).

Fingolimod: Treatment acceptance was evaluated in an analysis of patients (n=149, mean age 41.5 years) enrolled in the Canadian fingolimod patient support program treated with dimethyl fumarate (DMF) or teriflunomide immediately prior to fingolimod (Grand’Maison et al. ECTRIMS 2015; abstract P532). A majority (55.7%) switched therapies due to poor tolerability. At the time of the analysis, mean duration on fingolimod was 190 days, and 91.3% were continuing on therapy. Five patients (3%) stopped treatment due to adverse effects after the first dose.

Dimethyl fumarate: Three single-centre studies have examined the prevalence of persistent lymphopenia during DMF treatment, which may be associated with an increased risk of progressive multifocal leukoencephalopathy (PML). In the DEFINE trial of DMF, there was a 4% incidence of grade 3 lymphopenia, defined as absolute lymphocyte count < 0.5 x 109/L (Gold et al. N Engl J Med 2012;367:1098-107). A retrospective analysis of 323 patients in Portland, Oregon, found that ALC dropped below 0.5 at some point in 8.67% of patients (Smoot et al. ECTRIMS 2015; abstract P610). Mean duration of DMF exposure was 17.5 months. Older patients (58.7 vs. 48.1 years) had a significantly higher risk of lymphopenia.

At the Seattle MS centre, one-third had a reduced lymphocyte count; the incidence of grade III lymphopenia was 5.6% (Romba et al. ECTRIMS 2015; abstract P1130). Dose reductions to 240 mg/day did not improve lymphopenia and treatment was discontinued.

A similar retrospective analysis in Glasgow found ALC < 0.5 in 11 of 174 patients (6.3%) (MacDougall et al. ECTRIMS 2015; abstract P624). Two patients continued to have persistent low lymphocyte counts (0.5 and 0.9 x 109/L) six months after stopping DMF.

Fingolimod vs. DMF: The Rocky Mountain MS Center in Colorado retrospectively analysed data for 809 MS patients (mean age 45-47 years) on treatment with either fingolimod or DMF for at least one year (Vollmer et al. ECTRIMS 2015; abstract P1049). Mean duration of MS was 11 years. Overall, 6.3% of patients in the fingolimod group and 6.6% in the DMF group experienced a relapse. In the first year of treatment, 19.6% of fingolimod-treated patients and 25.2% of DMF-treated patients discontinued therapy (adjusted odds ratio 1.548 favouring fingolimod). Median time to discontinuation was 5 and 4 months, respectively. The discontinuation rate due to adverse events was 12.3% with fingolimod and 16.3% with DMF. Discontinuation rates due to new disease activity (relapse and/or new MRI lesions) were 3.8% and 6.5%, respectively.

Alemtuzumab: Data on pregnancy outcomes and infection risk were collected for 86 patients treated with alemtuzumab in open-label studies in Cambridge, UK, from 1999-2015 (McCarthy et al. ECTRIMS 2015; abstract P553). Median follow-up was 10 years. During that period, six patients (0.69%/year) required hospitalization for infections (4 cases of pneumonia; one case each of pyelonephritis and upper respiratory tract infection). Seventeen patients (1.98%/year) had varicella zoster virus reactivation. A total of 18 babies were born to 13 women. The median time from last alemtuzumab course to birth was 33 months (range 13-122 months). All babies were healthy and delivered without complications. Two women had a miscarriage but subsequently had successful pregnancies. No risk of miscarriage or fetal abnormality was observed.

Natalizumab: An Italian study examined whether pregnancy will prevent disease reactivation following discontinuation of natalizumab (Portaccio et al. ECTRIMS 2015; abstract 482). During the period 2010-2014, there were 52 pregnancies in patients exposed to natalizumab < 10 weeks prior to conception. There were 39 live births, 10 spontaneous abortions and three scheduled abortions. Overall, 14 of 39 women (35.8%) experienced a relapse during pregnancy, which was higher than the 13.3% incidence reported in an Italian study of pregnancies following IFNbeta exposure (Amato et al. Neurology 2010;75:1794-1802). The rate of spontaneous abortion was also significantly higher following natalizumab exposure (20.5%) compared to prior IFNbeta exposure (8.0%). The authors concluded that pregnancy does not protect against disease reactivation following natalizumab withdrawal.

Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada

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