Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study

AbstractBackgroundTo further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW).MethodsAnonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997–2009) of study participants (who received subcutaneous interferon β-1a before age 18years) from the US and ROW. Samples were stratified by age (preadolescents [<12years] and adolescents [12–17years]).ResultsUS adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5kg/m2), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon β-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon β-1a to another DMT before the end of the observation period.ConclusionsThis retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon β-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance

No difference in radiologic outcomes for natalizumab patients treated with extended interval dosing compared with standard interval dosing: Real-world evidence from MS PATHS

BACKGROUND: Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy. METHODS: Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID + SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons. RESULTS: The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p = 0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p = 0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p = 0.566) and -0.11% (-0.25%, -0.10%; p = 0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p\u3c0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p\u3c0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p = 0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p\u3c0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison. CONCLUSIONS: The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics

Adverse Childhood Experiences Are Linked to Age of Onset and Reading Recognition in Multiple Sclerosis

BackgroundAdverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood.ObjectiveTo investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS).MethodsSixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation.ResultsAdverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset (r = –0.30, p = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) (r = –0.25, p = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT).ConclusionChildhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS

Subcutaneous Interferon Beta-1a inPediatric Multiple Sclerosis: A Retrospective Study

To expand current knowledge, we examined the safety and tolerability of subcutaneous interferon b-1a in patients with pediatriconset multiple sclerosis. Records from 307 patients who had received at least 1 injection of subcutaneous interferon b-1a for demyelinating events when aged younger than 18 years were reviewed. Overall, 168 (54.7%) patients had at least 1 prespecified medical event related to or under close monitoring with subcutaneous interferon b-1a or specific to pediatric patients, 184 (59.9%) had nonserious medical events related to treatment or of unknown causality, and 12 (3.9%) had serious medical events irrespective of causality. The most common laboratory abnormalities were increased alanine (74/195; 37.9%) and aspartate aminotransferase levels (59/194; 30.4%). Annualized relapse rates were 1.79 before treatment and 0.47 during treatment. In conclusion, adult doses of subcutaneous interferon b-1a (44 and 22 mg, 3 times weekly) were well tolerated in pediatric patients and were associated with reduced relapse rates

Neuropsychology of multiple sclerosis: Looking back and moving forward

The neuropsychological aspects of multiple sclerosis (MS) have evolved over the past three decades. What was once thought to be a rare occurrence, cognitive dysfunction is now viewed as one of the most disabling symptoms of the disease, with devastating effects on patients' quality of life. This selective review will highlight major innovations and scientific discoveries in the areas of neuropathology, neuroimaging, diagnosis, and treatment that pertain to our understanding of the neuropsychological aspects of MS. Specifically, we focus on the recent discovery that MS produces pathogical lesions of gray matter (GM) that have consequences for cognitive functions. Methods for imaging these GM lesions in MS are discussed along with multimodal imaging studies that integrate structural and functional imaging methods to provide a better understanding of the relationship between cognitive test performance and functional reserve. Innovations in the screening and comprehensive assessment of cognitive disorders are presented along with recent research that examines cognitive dysfunction in pediatric MS. Results of innovative outcome studies in cognitive rehabilitation are discussed. Finally, we highlight trends for potential future innovations over the next decade

Gait and Functional Mobility in Multiple Sclerosis: Immediate Effects of Transcranial Direct Current Stimulation (tDCS) Paired With Aerobic Exercise

Walking impairments are a debilitating feature of multiple sclerosis (MS) because of the direct interference with daily activity. The management of motor symptoms in those with MS remains a therapeutic challenge. Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation that is emerging as a promising rehabilitative tool but requires further characterization to determine its optimal therapeutic use. In this randomized, sham-controlled proof-of-concept study, we tested the immediate effects of a single tDCS session on walking and functional mobility in those with MS. Seventeen participants with MS completed one 20-min session of aerobic exercise, randomly assigned to be paired with either active (2.5mA, n = 9) or sham (n = 8) tDCS over the primary motor cortex (M1). The groups (active vs. sham) were matched according to gender (50% vs. 60% F), age (52.1 ± 12.85 vs. 54.2 ± 8.5 years), and level of neurological disability (median Expanded Disability Status Scale score 5.5 vs. 5). Gait speed on the 10-m walk test and the Timed Up and Go (TUG) time were measured by a wearable inertial sensor immediately before and following the 20-min session, with changes compared between conditions and time. There were no significant differences in gait speed or TUG time changes following the session in the full sample or between the active vs. sham groups. These findings suggest that a single session of anodal tDCS over M1 is not sufficient to affect walking and functional mobility in those with MS. Instead, behavioral motor response of tDCS is likely to be cumulative, and the effects of multiple tDCS sessions require further study

Cognitive function in multiple sclerosis improves with telerehabilitation: Results from a randomized controlled trial.

Cognitive impairment affects more than half of all individuals living with multiple sclerosis (MS). We hypothesized that training at home with an adaptive online cognitive training program would have greater cognitive benefit than ordinary computer games in cognitively-impaired adults with MS. This was a double-blind, randomized, active-placebo-controlled trial. Participants with MS were recruited through Stony Brook Medicine and randomly assigned to either the adaptive cognitive remediation (ACR) program or active control of ordinary computer games for 60 hours over 12 weeks. Training was remotely-supervised and delivered through a study-provided laptop computer. A computer generated, blocked stratification table prepared by statistician provided the randomization schedule and condition was assigned by a study technician. The primary outcome, administered by study psychometrician, was measured by change in a neuropsychological composite measure from baseline to study end. An intent-to-treat analysis was employed and missing primary outcome values were imputed via Markov Chain Monte Carlo method. Participants in the ACR (n = 74) vs. active control (n = 61) training program had significantly greater improvement in the primary outcome of cognitive functioning (mean change in composite z score±SD: 0·25±0·45 vs. 0·09±0·37, p = 0·03, estimated difference = 0·16 with 95% CI: 0·02-0·30), despite greater training time in the active control condition (mean±SD:56·9 ± 34·6 vs. 37·7 ±23 ·8 hours played, p = 0·006). This study provides Class I evidence that adaptive, computer-based cognitive remediation accessed from home can improve cognitive functioning in MS. This telerehabilitation approach allowed for rapid recruitment and high compliance, and can be readily applied to other neurological conditions associated with cognitive dysfunction. TRIAL REGISTRATION:Clinicaltrials.gov NCT02141386