Papers by Samuel F Hunter
Journal of the Neurological Sciences, Jun 1, 2016
Depression is common in patients with multiple sclerosis (MS), may confound evaluation of therape... more Depression is common in patients with multiple sclerosis (MS), may confound evaluation of therapeutic effectiveness and may be impacted by MS-specific treatments. First, to assess the impact on depressive symptoms of a switch to fingolimod versus remaining on an injectable disease-modifying therapy (iDMT) in a post-hoc analysis of prospectively collected data from the EPOC study. Secondly, to investigate the underlying Beck Depression Inventory-II (BDI-II) factor structure in patients with MS, and estimate treatment differences using the resulting subscales. EPOC was a 6-month, open-label study assessing patient-reported outcomes after switch from iDMT to oral fingolimod 0.5mg versus remaining on iDMT in 1053 patients with relapsing-remitting MS. At end of study (EOS), a greater proportion of patients on fingolimod versus iDMT no longer had BDI-II scores indicating depression (p<0.001). Fewer mildly and moderately symptomatic patients developed severe depressive symptoms, and fewer severely symptomatic patients continued to have scores indicating severe depression at EOS on fingolimod versus iDMT (p=0.027, p=0.038, p=0.030, respectively). Two BDI-II subscales were identified and labelled Somatic and Affective; fingolimod demonstrated more reduction on both subscales at EOS versus iDMTs (p<0.0001 and p=0.0001, respectively). A switch to fingolimod versus remaining on/switching to another iDMT was associated with an improvement in depressive symptoms in patients with relapsing-remitting MS.
Journal of the Neurological Sciences, Dec 1, 2019
The American Journal of Medicine, 2014
Brain Communications
Baclofen, a racemic GABA-B (GABAB) receptor agonist, is commonly used for the management of multi... more Baclofen, a racemic GABA-B (GABAB) receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the GABAB receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets have a dosing interval of 12 hours and have shown a favourable safety and efficacy profile in early-phase clinical development. The current Phase 3 study was designed to evaluate the efficacy and safety of arbaclofen extended-release tablets in patients with multiple sclerosis-related spasticity. In this multicentre, double-blind, placebo-controlled study, adults with multiple sclerosis-related spasticity were randomized to arbaclofen extended-release 40 mg/day, arbaclofen extended-release 80 mg/day or placebo for 12 weeks. The co-primary end-points wer...
Multiple Sclerosis Journal, 2019
Neurology. Clinical practice, 2016
Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsing-r... more Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsing-remitting multiple sclerosis (MS), is a disease-modifying therapy with potential immunomodulatory and neuroprotective effects. In clinical trials, DMF was associated with reduced white blood cell and absolute lymphocyte counts. Current US prescribing information recommends obtaining a complete blood count, including absolute lymphocyte count (ALC), before initiating and during DMF treatment. We conducted an integrated analysis of phase 2b/3/long-term extension studies of DMF in MS (N = 2,470) to characterize ALC profiles. Mean ALCs decreased by 30% during the first year and then plateaued, remaining above the lower limit of normal (LLN). Among patients treated ≥6 months (N = 2,099), 2.2% experienced ALCs <500 mm(3) persisting ≥6 months. ALCs remained ≥LLN in 84% and 76% of patients during the first 6 and 12 months, respectively; of these, 0.1% and 0%, respectively, developed ALCs <5...
The occurrence of a wasted tongue following a demy-elinating attack involving a medullary lesion ... more The occurrence of a wasted tongue following a demy-elinating attack involving a medullary lesion in neu-romyelitis optica spectrum disorders (NMOSDs) secondary to hypoglossal nerve involvement is unu-
Advances in Therapy, Feb 24, 2022
Introduction: Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS) ... more Introduction: Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS) with the same active metabolite as dimethyl fumarate (DMF). DRF has a safety/efficacy profile similar to DMF but with improved gastrointestinal (GI) tolerability and low (\ 1%) treatment discontinuation due to GI adverse events (AEs). Efficacy and safety outcomes in patients who switched to DRF from other
Journal of Neuroimaging, May 11, 2018
BACKGROUND AND PURPOSE: Evidence is needed to understand the effect of fingolimod on slowing down... more BACKGROUND AND PURPOSE: Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of active disease (NEAD). METHODS: MS and clinical outcome and MRI in the United States (MS-MRIUS) is a multicenter, retrospective study that included 590 relapsing-remitting MS patients, who initiated fingolimod, and were followed for a median of 16 months. Patients with active disease at baseline (245, 41.5%) were defined as those who had one or more relapses in the year previous starting fingolimod, and/or displayed gadolinium enhancing lesions(s) at baseline MRI scan, whereas patients with NEAD at baseline (345, 58.5%) did not fulfill these criteria. Annualized percentage brain volume change (PBVC) and percentage lateral ventricle volume change (PLVVC) over the follow-up were analyzed in both groups. RESULTS: Over the follow-up, the rate of PBVC was −.38% in active disease and −.25% in NEAD patients (P = .076), whereas PLLVC was 1.76% in active disease and .28% in NEAD patients (P = .046). No changes in timed 25-foot walk (P = .619) and Expanded Disability Status Scale (P = .275) scores or MRI lesion accumulation (P > 0.08) were detected, although the active disease group had a higher proportion of relapses during the follow-up period (P = .02).
Introduction: In clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were fre... more Introduction: In clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were frequent. Here, we assess the impact of thyroid AEs on health-related quality of life (HRQL) in alemtuzumab-treated patients with relapsingremitting multiple sclerosis (RRMS). Methods: In phase 3 CARE-MS I (NCT00530348) and II (NCT00548405) trials, patients with RRMS were administered alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients could participate in an extension study (NCT00930553) through year 6. HRQL was assessed at baseline and annually using the Functional Assessment of Multiple Sclerosis (FAMS), EuroQoL-5 Dimension Visual Analog Scale (EQ-5D VAS), and 36-Item Short-Form Survey (SF-36) questionnaires. Outcomes were Digital features To view digital features for this article go to
Neurology, 2016
OBJECTIVE: To evaluate the safety and tolerability of AERT over 1 year of treatment and the long-... more OBJECTIVE: To evaluate the safety and tolerability of AERT over 1 year of treatment and the long-term effects on spasticity. BACKGROUND Spasticity is common in MS and is associated with significant morbidity. The standard treatment is oral administration of baclofen, a γ-aminobutyric acid-b (GABA-b) receptor agonist. Baclofen is a racemic mixture and its biological activity is thought to be due to the R-enantiomer (arbaclofen). Therapeutic doses of baclofen can cause CNS side effects that may affect adherence and tolerability. AERT can reduce dosing frequency and adverse events. DESIGN/METHODS This was a multicenter, open label, single arm study that enrolled patients with spasticity due to MS. All subjects received AERT and were maintained on the highest tolerated dose up to 20 mg bid for up to a year. AERT was gradually withdrawn at the end of the maintenance period. The study assessed safety parameters and the severity of spasticity using Total Numeric-transformed Modified Ashwor...
Neurology, 2015
OBJECTIVE: Is improvement in EDSS following ALE therapy related to prior therapy in two years bef... more OBJECTIVE: Is improvement in EDSS following ALE therapy related to prior therapy in two years before ALE (e.g. interferon-beta vs. natalizumab)? BACKGROUND: Improvement following aggressive therapy challenges traditional concepts of neurodegeneration in higher disability. We reported retrospective, long-term outcomes after ALE in treatment-refractory, high-disability MS, with improved EDSS, relapse rate, and MS severity scale. The majority of patients improve in disability, and those stable or worsening generally have unchanged MS Severity Scores. Which patients realize improvement after more aggressive immunotherapy remains an open question, and whether outcomes after natalizumab or interferon-beta differ. DESIGN/METHODS: We retrospectively followed up a high disability, active (relapse and/or MRI) cohort on ALE therapy. A retrospective cohort ( n =29) >12 months ALE treatment was treated in the immediate pre-ALE epoch with interferon-beta (18/29) and natalizumab (7/29). Some in...
Neurology, 2014
OBJECTIVE: Assess ALE benefit in an active, disabled, treatment-refractory MS cohort as a rescue ... more OBJECTIVE: Assess ALE benefit in an active, disabled, treatment-refractory MS cohort as a rescue immunotherapy in long-term follow up. BACKGROUND: ALE, an anti-CD52, cytotoxic, monoclonal IgG, produces transient lymphopenia. Initial studies in the 1990s at Cambridge suggested less benefit of ALE in patients with progressive features; however, following regulatory approval ALE will likely be used for higher disability, active disease in highly treatment-experienced patients, given the ALE risk-benefit ratio. This profile differs from subjects participating in previous phase II/III clinical trials. Our goal is to address the gap in knowledge of likely outcomes for these patient demographics. DESIGN/METHODS: We evaluated a cohort retrospectively of disabled (EDSS median ~5.0), ALE-experienced relapsing MS subjects ( n =30) entering a phase I protocol for long-term ALE therapy and monitoring (2-7 y follow-up). Outcomes are annualized relapse rate (ARR), EDSS change from baseline, MS Sev...
SSRN Electronic Journal, 2022
Advances in Therapy, 2022
Introduction: Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS) ... more Introduction: Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS) with the same active metabolite as dimethyl fumarate (DMF). DRF has a safety/efficacy profile similar to DMF but with improved gastrointestinal (GI) tolerability and low (\ 1%) treatment discontinuation due to GI adverse events (AEs). Efficacy and safety outcomes in patients who switched to DRF from other
Drugs in Context, Jan 22, 2021
The authors wish to make the following corrections to their article: Wan GJ, Chopra I, Niewoehner... more The authors wish to make the following corrections to their article: Wan GJ, Chopra I, Niewoehner J, Hunter SF. Cost per response analysis of repository corticotropin injection versus other alternative treatments for acute exacerbations of multiple sclerosis.
Multiple Sclerosis and Related Disorders, 2020
BACKGROUND Injectable disease-modifying therapies (iDMTs) are often used as first-line treatments... more BACKGROUND Injectable disease-modifying therapies (iDMTs) are often used as first-line treatments for relapsing multiple sclerosis. Fingolimod is frequently used following treatment with iDMTs. Whether prior iDMT treatment impacts the effectiveness of subsequent fingolimod therapy is unclear. Here, we assessed switching from iDMTs to fingolimod, and the impact of treatment history on fingolimod escalation using data from the 12-month 'Prospective, Randomized, active-controlled, open-label study to Evaluate patient retention on Fingolimod versus approved first-line disease-modifying thErapies in adults with Relapsing-remitting Multiple Sclerosis' (PREFERMS). The study design and results at the end of randomized treatment (EoRT) in PREFERMS have been published. METHODS Both treatment-naïve patients and those who had previously received an iDMT were eligible for enrolment in PREFERMS, and one treatment switch was permitted on study. Pre-specified exploratory analyses compared outcomes in those randomized to fingolimod or to an iDMT at end of study (EoS), which included time spent on randomized and on switch treatment. Post hoc exploratory analyses (unadjusted for multiplicity owing to the large number of comparisons) among patients randomized to an iDMT who switched to fingolimod, compared outcomes longitudinally before (EoRT) and after (EoS) switching, and compared outcomes at EoRT and EoS among subgroups stratified by iDMT-treatment history. Outcomes included brain volume, various measures of gadolinium-enhancing [Gd+] lesion counts, annualized relapse rate (ARR), Symbol Digit Modalities Test (SDMT) score, patient-reported treatment satisfaction using the Medication Satisfaction Questionnaire (MSQ) and adverse event (AE) rates. RESULTS At EoS, 255 of 439 patients randomized to an iDMT had switched to fingolimod and 27 of 436 patients randomized to fingolimod had switched to an iDMT. By EoS, 44.2% of total treatment exposure in the iDMT group was to fingolimod and the mean time spent on fingolimod in this group was 220 days (approximately 7 months). Outcomes in the fingolimod group at EoS (brain volume, changes in Gd+ lesion counts, ARR, oral SDMT score and MSQ score) were similar to those seen at EoRT, but in the iDMT group these outcomes were more favorable at EoS than at EoRT and were similar to rates seen in the fingolimod group. Among patients who switched from iDMT to fingolimod, there were longitudinal improvements in ARR (EoRT, 0.3 [95% confidence interval (CI), 0.2-0.4]; EoS, 0.2 [0.1-0.3]; odds ratio, 0.5 [0.3-0.9]) and in treatment satisfaction (proportion of patients with MSQ > 5; EoRT, 67.4%; EoS, 90.4%; odds ratio, 5.7 [95% CI, 3.4-9.4]) after fingolimod treatment, and changes in brain volume, Gd+ lesion count, and AEs or AEs causing discontinuation were also more favorable at EoS than at EoRT. In all patient groups stratified by iDMT-treatment history, differences in outcomes narrowed or disappeared after fingolimod treatment. CONCLUSION These analyses indicate that patients in PREFERMS had improved outcomes within months of switching to fingolimod from an iDMT and that improvements occurred irrespective of the number of iDMTs previously administered. These data provide a unique opportunity to explore clinical, radiological and safety outcomes associated with a range of clinically relevant treatment pathways.
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Papers by Samuel F Hunter