IM interferon β-1a delays definite multiple sclerosis 5 years after a first demyelinating event

Kinkel, R. Philip; Kollman, Craig; O’Connor, Paul; Murray, Thomas Jock; Simon, Jack H.; Arnold, Douglas L.; Bakshi, Rohit; Weinstock-Gutman, Bianca; Brod, Staley A.; Cooper, Joanna K.; Duquette, Pierre; Eggenberger, Eric; Felton, Warren L.; Fox, Robert; Freedman, Mark S.; Galetta, Steven; Goodman, Andrew; Guarnaccia, Joseph; Hashimoto, S. A.; Horowitz, Steven H.; Javerbaum, Jeffrey; Kasper, Lloyd H.; Kaufman, Michael J.; Kerson, Lloyd; Mass, Michelle; Rammohan, Kottil; Reiss, Merrell; Rolak, Loren A.; Rose, John; Scott, Thomas Allan; Selhorst, John B.; Shin, R.T.; Smith, Craig H.; Stuart, William D.; Thurston, Stephen P.; Wall, Michael

doi:10.1212/01.wnl.0000200778.65597.ae

Cited by 201 publications

(26 citation statements)

References 9 publications

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“…Follow-ups occurred on days 4, 15, and 30, weeks 7, 13, and 19, months 6 and 12, and then yearly [19]. The Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance (CHAMPIONS) study was an open-label extension of Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) [20], [21]. CHAMPS enrolled subjects without a prior episode of neurologic dysfunction who were seen within 27 days of the onset of neurologic symptoms consistent with MS and had an abnormal brain MRI (≥2 clinically silent MS-consistent lesions).…”

Section: Methodsmentioning

confidence: 99%

Multiple Sclerosis Susceptibility Genes: Associations with Relapse Severity and Recovery

et al. 2013

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ObjectivePatients with early multiple sclerosis (MS) have stereotyped attack severity and recovery. We sought to determine if polymorphisms in MS susceptibility genes are associated with these attack features or with the risk of a second attack.Methods503 white subjects evaluated within a year of MS onset were included in the study. The severity of and recovery from the first two attacks were determined based on published definitions. Seventeen MS susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each polymorphism was evaluated in multivariate ordinal models, adjusted for the other polymorphisms, for its association with attack severity and recovery. We also assessed if these polymorphisms were associated with increased risk of a second attack.ResultsThe MPHOSPH9 polymorphism was associated with greater attack severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack severity. The CD6 polymorphism tended to be associated with increased odds of worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event within a year.ConclusionsSome MS susceptibility polymorphisms may be associated with attack severity, recovery, or frequency. Further characterization of these genes may lead to a better understanding of MS pathogenesis and to a more individualized treatment approach.

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Section: Methodsmentioning

confidence: 99%

Multiple Sclerosis Susceptibility Genes: Associations with Relapse Severity and Recovery

et al. 2013

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“…The manufacturer's submission stated that 30 µg of IM IFN-β-1a weekly is effective in reducing the relapse rate and disability progression compared with placebo, citing the MSCRG trial 200 and its observational extension 236 as evidence. The submission further stated that 30 µg of IM IFN-β-1a weekly is effective in delaying CDMS in patients with CIS, citing the CHAMPS trial 172 and its open-label extension 237 in support of this.…”

Section: Summary Of the Teva Pharmaceutical Industries Submissionmentioning

confidence: 99%

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation

Melendez‐Torres

Auguste

Armoiry

et al. 2017

Health Technol Assess

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Background At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. Objectives To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing–remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. Review methods Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health’s risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. Results In total, 6420 publications were identified, of which 63 relating to 35 randomised controlled trials (RCTs) were included. In total, 86% had a high risk of bias. There was very little difference between drugs in reducing moderate or severe relapse rates in RRMS. All were beneficial compared with BSC, giving a pooled rate ratio of 0.65 [95% confidence interval (CI) 0.56 to 0.76] for ARR and a hazard ratio of 0.70 (95% CI, 0.55 to 0.87) for time to disability progression confirmed at 3 months. NMA suggested that 20 mg of GA given subcutaneously had the highest probability of being the best at reducing ARR. Three separate cost-effectiveness searches identified > 2500 publications, with 26 included studies informing the narrative synthesis and model inputs. In the base case using a modified RSS the mean incremental cost was £31,900 for pooled DMTs compared with BSC and the mean incremental quality-adjusted life-years (QALYs) were 0.943, giving an ICER of £33,800 per QALY gained for people with RRMS. In probabilistic sensitivity analysis the ICER was £34,000 per QALY gained. In sensitivity analysis, using the assessment group inputs gave an ICER of £12,800 per QALY gained for pooled DMTs compared with BSC. Pegylated IFN-β-1 (125 µg) was the most cost-effective option of the individual DMTs compared with BSC (ICER £7000 per QALY gained); GA (20 mg) was the most cost-effective treatment for CIS (ICER £16,500 per QALY gained). Limitations Although we built a de novo model for CIS that incorporated evidence from our systematic review of clinical effectiveness, our findings relied on a population diagnosed with CIS before implementation of the revised 2010 McDonald criteria. Conclusions DMTs were clinically effective for RRMS and CIS but cost-effective only for CIS. Both RCT evidence and RSS data are at high risk of bias. Research priorities include comparative studies with longer follow-up and systematic review and meta-synthesis of qualitative studies. Study registration This study is registered as PROSPERO CRD42016043278. Funding The National Institute for Health Research Health Technology Assessment programme.

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“…Several major placebo-controlled clinical trials, ETOM,9 CHAMPS,10 BENEFIT,11 and PreCISe,12 have shown that interferon (IFN) β-1a (Rebif ® ; EMD Serono, Inc., Rockland, MA, USA) (Avonex ® ; Biogen Idec, Cambridge, MA, USA), IFN β-1b (Betaseron ® ; Bayer Healthcare Pharmaceuticals, Inc., Montville, NJ, USA), or glatiramer acetate (Copaxone ® ; TEVA Neuroscience, Inc., Kansas City, MO, USA) therapy in CIS patients postpones the time to clinically definite multiple sclerosis for some. A 3-year extension of the BENEFIT13 study and a 5-year extension of the CHAMPS study, CHAMPION,14 have confirmed benefits of early treatment.…”

Section: Epidemiologymentioning

confidence: 84%

New approaches in the management of multiple sclerosis

Barten

Allington

Procacci³

et al. 2010

DDDT

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Multiple sclerosis (MS) is a central nervous system chronic inflammatory disease that is characterized by an extensive and complex immune response. Scientific advances have occurred in immunology, pathophysiology, and diagnostic and clinical assessment tools, and recent discovery of unique therapeutic targets has spurred numerous Phase II and Phase III clinical trials. Reductions in MS relapse rates and improvements in T2 or gadolinium-enhancing lesion burdens have been reported from Phase III trials that include fingolimod, alemtuzumab, cladribine, and rituximab. Promising Phase II trial data exist for teriflunomide, daclizumab, laquinimod, and fumarate. The optimism created by these favorable findings must be tempered with evaluation of the adverse effect profile produced by these new agents. Given the discovery of progressive multifocal leukoencephalopathy with the use of natalizumab, ongoing vigilance for rare and life-threatening reactions due to new agents should be paramount. Patients with MS often experience difficulty with ambulation, spasticity, and cognition. Recent clinical trial data from two Phase III dalfampridine-SR trials indicate certain patients receive benefits in ambulation. This article provides an overview of data from clinical trials of newer agents of potential benefit in MS.

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IM interferon β-1a delays definite multiple sclerosis 5 years after a first demyelinating event

Abstract: These results support the use of IM interferon beta-1a after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.

Cited by 201 publications

References 9 publications

Multiple Sclerosis Susceptibility Genes: Associations with Relapse Severity and Recovery

Multiple Sclerosis Susceptibility Genes: Associations with Relapse Severity and Recovery

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation

New approaches in the management of multiple sclerosis

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