Faculty Bibliography
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630
Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis
BACKGROUND:BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing-remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate). METHODS:In this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing-remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The study was not designed to test the superiority or noninferiority of BG-12 versus glatiramer acetate. RESULTS:At 2 years, the annualized relapse rate was significantly lower with twice-daily BG-12 (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice-daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate significantly reduced the numbers of new or enlarging T(2)-weighted hyperintense lesions (all P<0.001) and new T(1)-weighted hypointense lesions (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12 versus glatiramer acetate, differences were not significant except for the annualized relapse rate (thrice-daily BG-12), new or enlarging T(2)-weighted hyperintense lesions (both BG-12 doses), and new T(1)-weighted hypointense lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events (with BG-12) and injection-related events (with glatiramer acetate). There were no malignant neoplasms or opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG-12. CONCLUSIONS:In patients with relapsing-remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.).
PMID: 22992072
ISSN: 1533-4406
CID: 5347972
Regression-based norms improve the sensitivity of the National MS Society Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS)
The National Multiple Sclerosis Society Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS) was designed to detect cognitive impairment in children and adolescents with multiple sclerosis. One weakness of the battery is the reliance on published manual-based normative samples varying in size and quality. These primary sources base interpretation on discrete age bands, a practice which may be particularly problematic during periods of rapid development in childhood and adolescence. A further impediment to valid NBPMS interpretation is the lack of control for demographic factors other than age. We endeavored to develop regression-based norms for the NBPMS by gathering a demographically balanced sample of 102 healthy control children and using their performance to derive normalization, controlling for multiple demographic variables (i.e., age, age(2), gender, parent education). The regression-based normative equations were applied to the performance of 51 children with MS. For many of the major test scores, the regression-based norms more readily detected impairment. As in the case of adult MS, these results indicate that regression-based norms offer interpretive benefits over their manual-based counterparts.
PMID: 22849345
ISSN: 1744-4144
CID: 2234892
A phase 1b, randomised, placebo-controlled, multiple-dose study of human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis [Meeting Abstract]
ISI:000328702201026
ISSN: 1477-0970
CID: 2234122
REMOTE COMMON VIRAL INFECTIONS ARE NOT PREDICTIVE OF SUBSEQUENT RELAPSE RISK IN PEDIATRIC MULTIPLE SCLEROSIS [Meeting Abstract]
ISI:000308138200025
ISSN: 1352-4585
CID: 2234082
Multiple sclerosis genetic susceptibility factors rs4648356 and rs11154801 are associated with relapse rate in paediatric patients [Meeting Abstract]
ISI:000328702200085
ISSN: 1477-0970
CID: 2234102
Safety of adult doses of subcutaneous interferon-beta-1a in children and adolescents with multiple sclerosis: results of the REPLAY study [Meeting Abstract]
ISI:000328702200131
ISSN: 1477-0970
CID: 2234112
Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) [Guideline]
BACKGROUND: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. OBJECTIVE: To recommend a brief cognitive assessment for multiple sclerosis (MS) that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use. METHODS: An expert committee of twelve members representing the main cultural groups that have so far contributed considerable data about MS cognitive dysfunction was convened. Following exhaustive literature review, peer-reviewed articles were selected to cover a broad spectrum of cultures and scales that targeted cognitive domains vulnerable to MS. Each was rated by two committee members and candidates scales were rated on psychometric qualities (reliability, validity, and sensitivity), international application, ease of administration, feasibility in the specified context, and acceptability to patients. RESULTS: The committee recommended the Symbol Digit Modalities Test, if only 5 minutes was available, with the addition of the California Verbal Learning Test - Second Edition and the Brief Visuospatial Memory Test - Revised learning trials if a further 10 minutes could be allocated for testing. CONCLUSIONS: A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.
PMCID:3546642
PMID: 22190573
ISSN: 1477-0970
CID: 2233972
Subcutaneous interferon beta-1a in paediatric patients with multiple sclerosis: regional outcomes in an international retrospective study (REPLAY) [Meeting Abstract]
ISI:000312192300170
ISSN: 1352-4585
CID: 2234292
Brief International Cognitive Assessment for MS (BICAMS): reliability and identifying statistically reliable change [Meeting Abstract]
Background: Approximately one-third of those with pediatric-onset multiple sclerosis (MS) experience cognitive impairment. Less is known concerning their change in cognitive functioning over time. Objective: Changes in cognitive function over time were measured in the largest pediatric cohort to date through the US Network of Pediatric MS Centers. Methods: A total of 67 individuals with pediatric MS (n=62) or clinically isolated syndrome (CIS, n=5), ranging from 8-17 years of age (mean age standard deviation (SD)=14.37+/-2.02) completed initial and follow-up neuropsychological testing after an average of 1.64+/-0.63 years apart. The nine tests administered measure general intellect, attention and working memory, verbal memory, visuomotor integration, language, and executive functioning. Results: Rate of impairment (having one-third or more scores in the impaired range) was 37% at baseline and 33% at follow-up. Tests commonly impaired were measures of visuomotor integration, speeded processing, and attention. Most tested did not decline over two years. There was no clear pattern of change on any specific measure. Conclusion: Findings suggest that, over short timeframes, stable or even improved performances on measures of cognitive ability can occur. Pediatric MS may instead prevent expected age-related cognitive gains.
ISI:000328702201003
ISSN: 1477-0970
CID: 2234132
Evaluation of vitamin D-related parameters in a multinational paediatric multiple sclerosis case-control study [Meeting Abstract]
ISI:000328702202041
ISSN: 1477-0970
CID: 2234142
