| 1. |
- Beiske, A G, et al.
(author)
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Health-related quality of life in secondary progressive multiple sclerosis.
- 2007
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:3, s. 386-92
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Journal article (peer-reviewed)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS.
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| 2. |
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| 3. |
- Sandberg Wollheim, Magnhild, et al.
(author)
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Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis.
- 2005
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 65:6, s. 802-806
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Journal article (peer-reviewed)abstract
- Background: Although patients with multiple sclerosis (MS) are advised to stop interferon (IFN) beta-1a therapy before becoming pregnant, some patients become pregnant while on treatment. Methods: We examined individual patient data from eight clinical trials with IFN beta-1a. Results: Of 3,361 women in the studies, 69 pregnancies were reported, of which 41 were patients receiving (or who had stopped receiving within 2 weeks prior to conception) IFN beta-1a (in utero exposure group), 22 were patients who discontinued IFN beta-1a treatment more than 2 weeks before conception (previous exposure group), and six were patients receiving placebo. The 41 in utero exposure pregnancies resulted in 20 healthy full-term infants, one healthy premature infant, nine induced abortions, eight spontaneous abortions, one fetal death, and one congenital anomaly (hydrocephalus). One patient was lost to follow-up. The 22 previous exposure pregnancies resulted in 20 full-term healthy infants, one healthy premature infant, and one birth-related congenital anomaly (Erb palsy) Conclusions: The majority (21/31) of pregnancies that had the potential to go to full term produced healthy infants. The rate of spontaneous abortion was higher, but not significantly so, in the in utero exposure group compared to general population estimates. Until more exposure data become available, patients remain advised to stop IFN beta therapy before becoming pregnant.
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| 4. |
- Andersen, Oluf, 1941, et al.
(author)
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Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis
- 2004
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In: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 75:5, s. 706-710
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Journal article (peer-reviewed)
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| 5. |
- Beiske, A. G., et al.
(author)
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Health-related quality of life in secondary progressive multiple sclerosis
- 2007
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In: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 13:3, s. 386-392
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Journal article (peer-reviewed)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta 1a (IFN-beta 1a), 22 mu g subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta 1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS influenced subdimensions such as pain, sleep and emotional reactions. Increased focus on optimizing symptomatic treatment and psychosocial patient care could improve patients' HRQoL.
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| 7. |
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| 8. |
- Ciusani, E., et al.
(author)
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Analysis of HLA-Class II DQA1, DQB1, DRB1 and DPB1 in Italian Multiple Sclerosis Patients
- 1995
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In: European journal of immunogenetics. - 0960-7420 .- 1365-2370. ; 22:2, s. 171-178
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Journal article (peer-reviewed)abstract
- We studied the allelic constitution at the HLA class II DQA1, DQB1, DRB1 and DPB1 in 94 Italian multiple sclerosis (MS) patients and 98 controls. No significant increase in the frequency of DR2 alleles was detected among MS patients, as previously observed both in European and some Italian studies. A slight increase was found for the DQA1*0301 and DQB1*0602 alleles in the MS patients. No significant association was found with the glutamine residue at position 34 of the DQ alpha chain, which was noted previously in MS patients from northern Europe.
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| 9. |
- Clanet, M, et al.
(author)
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A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS
- 2002
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In: Neurology. - 1526-632X. ; 59:10, s. 1507-1517
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Journal article (peer-reviewed)abstract
- Background: Interferon beta-1a (IFNbeta-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNbeta-1a is not known. Objective: To determine whether IFNbeta-1a 60 mug IM once weekly is more effective than IFNbeta-1a 30 mug IM once weekly in reducing disability progression in relapsing MS. Methods: In a double-blind, parallel-group, dose-comparison study, 802 patients with relapsing MS from 38 centers in Europe were randomized to IFNbeta-1a 30 mug (n = 402) or 60 mug (n = 400) IM once weekly for greater than or equal to36 months. The primary endpoint was disability progression, defined as time to a sustained increase of greater than or equal to1.0 point on the Expanded Disability Status Scale (EDSS) persisting for 6 months. Additional endpoints included relapses, MRI, safety, immunogenicity, and subgroup analyses of disability progression. Results: Both groups showed equal rates of disability progression (hazard ratio, 0.96; 95% CI, 0.77 to 1.20; p = 0.73). In both groups the proportion of subjects with progression of disability by 36 months estimated from Kaplan-Meier curves was 37%. No dose effects were observed on any of the secondary clinical endpoints. Only one MRI measure at one time point, number of new or enlarging T2 lesions at month 36 compared with month 24, showed a difference favoring the 60-mug dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60-mug group. The incidences of neutralizing antibodies (titers greater than or equal to20) were 2.3% in the 30-mug group and 5.8% in the 60-mug group. Conclusion: There was no difference between IFNbeta-1a 30 mug and 60 mug IM in clinical or MRI measures.
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| 10. |
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| 11. |
- Dai, Y, et al.
(author)
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Analysis of an interferon-gamma gene dinucleotide-repeat polymorphism in Nordic multiple sclerosis patients
- 2001
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 7:3, s. 157-163
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Journal article (peer-reviewed)abstract
- The proinflammatory cytokine interferon (IFN)-γ has been shown to influence the course of multiple sclerosis (MS). The IFN-γ (IFNG) contains a multiallelic dinucleotide repeat in intron l. To investigate whether alleles at this locus influence susceptibility to MS, we performed linkage and familial association analyses on 100 sibling pairs from four Nordic countries, and case-control association analysis on 220 intermediately disabled sporadic MS patients and 266 controls. To determine the effect of the polymorphism on disease outcome, we compared genotype frequencies in the most and least disabled octiles of a total cohort of 913 cases. We also measured IFN-γ mRNA levels in unstimulated peripheral blood mononuclear cells from 46 MS patients and 27 controls grouped according to IFNG intron l genotype. Both nonparametric linkage analysis and transmission disequilibrium testing of the 100 sibling pairs produced negative results. Genotype frequencies for intermediate-MS patients did not differ significantly from those for controls; nor did genotype frequencies in the benign-MS octile differ significantly from those in the severe-MS octile. Comparison of IFN-γ mRNA levels in genotype-conditioned subgroups revealed no significant differences. Thus, alleles at the IFNG intron l dinucleotide repeat appear to affect neither MS susceptibility and severity nor IFN-γ mRNA expression in vivo.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Akesson, E, et al.
(author)
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A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis
- 2002
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In: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 3:5, s. 279-285
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Journal article (peer-reviewed)abstract
- Genetic factors influence susceptibility to multiple sclerosis but the responsible genes remain largely undefined, association with MHC class II alleles being the only established genetic feature of the disease. The Nordic countries have a high prevalence of multiple sclerosis, and to further explore the genetic background of the disease, we have carried out a genome-wide screen for linkage in 136 sibling-pairs with multiple sclerosis from Denmark, Finland, Norway and Sweden by typing 399 microsatellite markers. Seventeen regions where the lod score exceeds the nominal 5% significance threshold (0.7) were identified-1q11-24, 2q24-32, 3p26.3, 3q21.1, 4q12, 6p25.3, 6p21-22, 6q21, 9q34.3, 10p15, 10p12-13, 11p15.5, 12q21.3, 16p13.3, 17q25.3, 22q12-13 and Xp22.3. Although none of these regions reaches the level of genome-wide significance, the number observed exceeds the 10 that would be expected by chance alone. Our results significantly add to the growing body of linkage data relating to multiple sclerosis.
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| 18. |
- Bergkvist, My, et al.
(author)
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No evidence for genetic linkage between development of multiple sclerosis and components of the IFN system and the JAK-STAT pathway.
- 2004
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In: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 10:1, s. 87-88
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Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Several observations suggest that the interferon system may be of interest in the study of MS development. To investigate whether polymorphism in components of the IFN system and the JA K-STAT pathway influence susceptibility to MS, we performed a linkage analysis between polymorphic loci in or close to the IFN gamma, IFN gamma recepto r, IFN alpha/beta recepto r, JA K 1, STAT 1 and STAT 3 genes in 27 Swedish families with at least two members having MS. Tests for transmission disequilibrium and nonparametric linkage analysis gave negative results. We found no evidence for linkage between MS and any of these loci.
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| 19. |
- Kappos, L, et al.
(author)
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Neutralizing antibodies and efficacy of interferon beta-1a - A 4-year controlled study
- 2005
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In: Neurology. - 1526-632X. ; 65:1, s. 40-47
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Journal article (peer-reviewed)abstract
- Objective: To determine the incidence and clinical significance of neutralizing antibody (NAb) formation in patients with relapsing multiple sclerosis ( MS) who participated in the European Interferon Beta-1a IM Dose-Comparison Study. Methods. Patients were randomized to treatment with interferon beta-1a (IFN beta-1a) 30 mu g or 60 mu g IM once weekly for up to 4 years. Serum samples obtained at baseline and every 3 months thereafter were screened for the presence of IFN binding antibodies by ELISA. Patients whose results were seropositive on ELISA were screened for the presence of NAbs using an antiviral cytopathic effect assay. Patients were considered to be positive for NAbs ( NAb+) if the baseline NAb titer was 0 and two or more consecutive postbaseline titers were >= 20. Patients were considered to be negative for NAbs ( NAb -) if the baseline NAb titer was 0 and all postbaseline NAb titers were < 5. Results: The proportion of patients who became NAb + was lower in patients who received 30 mu g of IFN beta-1a than in those who received 60 mu g (7/400 [1.8%] vs 19/395 [4.8%]; p = 0.02). The mean time to NAb + status was 14.5 +/- 6.2 months. Compared with patients who remained NAb -, NAb + patients showed the following: higher relapse rates from months 12 to 48 ( p = 0.04), higher rate of mean change ( worsening) in Expanded Disability Status Scale score from baseline to month 48 ( p = 0.01), greater number of T1 gadolinium-enhanced lesions at months 24 and 36 ( p = 0.02 and 0.03), and greater accrual of new or enlarging T2 lesions from month 12 to months 24 and 36 ( p = 0.05 and 0.09) Conclusions: Neutralizing antibodies ( NAbs) to interferon beta-1a (IFN beta-1a), as observed with other IFN beta s used in the treatment of multiple sclerosis, reduce the therapeutic benefits measured by relapses and MRI activity. Data from this study also suggest NAbs to IFN beta-1a reduce treatment benefits as measured by change in Expanded Disability Status Scale score.
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| 20. |
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| 21. |
- Nilsson, Petra, et al.
(author)
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Cognitive dysfunction 24-31 years after isolated optic neuritis.
- 2008
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In: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 14, s. 913-918
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Journal article (peer-reviewed)abstract
- Objective Cognitive dysfunction is common in multiple sclerosis (MS), but long-term data on cognition in patients with clinically isolated syndromes are sparse. Methods We determined cognitive functions in 22 patients 44-75 years old diagnosed with optic neuritis 24-31 years earlier but had no further clinical bouts and had not progressed clinically to MS. We used a neuropsychological test battery covering nine cognitive domains. Magnetic resonance imaging (MRI) of the brain had been performed earlier and was normal in six patients and showed two or more white matter abnormalities compatible with demyelinating lesions in 16 patients. Results On neuropsychological testing, one patient was within normal range on all tests, six subjects showed borderline results, and 15 patients (68%) showed significantly impaired performance in at least one cognitive domain. Seven patients showed significant impairment in two or more domains. Executive function, visuo-spatial ability, and information processing speed were the most frequently affected domains. There was no apparent correlation between MRI findings and cognitive function. Conclusions We conclude that cognitive dysfunction is common in patients many years after clinically isolated optic neuritis. Cognitive dysfunction was found even in patients who had no apparent demyelinating lesions on follow-up MRI.
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| 22. |
- Nilsson, Petra, et al.
(author)
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The role of MRI of the brain and spinal cord, and CSF examination for the diagnosis of primary progressive multiple sclerosis
- 2007
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 14:11, s. 1292-1295
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Journal article (peer-reviewed)abstract
- The clinical applicability of the revised McDonald diagnostic criteria of primary progressive multiple sclerosis (PPMS) was assessed in 17 patients with a longstanding PPMS diagnosis (mean 15 years). All patients were re-evaluated with clinical examinations, magnetic resonance imaging (MRI) of the brain and the spinal cord, extensive laboratory tests, and 12 patients underwent cerebrospinal fluid (CSF) examination. No diagnosis more likely than PPMS was disclosed. All patients had brain and spinal cord lesions on MRI. In 15 patients the brain lesions and in 14 the spinal cord lesions fulfilled the revised McDonald criteria for positive scans. No contrast-enhancing lesion was observed despite administration of triple doses of gadolinium. In total, 12 patients fulfilled the revised McDonald MRI criteria for PPMS. Of the remaining five patients who incompletely fulfilled the revised MRI criteria, all had CSF findings supporting the diagnosis PPMS. Thus, CSF analysis was required in addition to MRI in about one-third of the patients to establish the diagnosis of PPMS.
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| 23. |
- Polman, CH, et al.
(author)
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Diagnostic criteria for multiple sclerosis: 2005 Revisions to the "McDonald Criteria"
- 2005
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In: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 58:6, s. 840-846
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Journal article (peer-reviewed)abstract
- New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.
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| 24. |
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| 25. |
- Schwid, SR, et al.
(author)
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Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis - The EVIDENCE study
- 2005
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In: Archives of Neurology. - 0003-9942. ; 62:5, s. 785-792
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Journal article (peer-reviewed)abstract
- Background: The EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study demonstrated that patients with multiple sclerosis (MS) who initiate interferon beta-la therapy with 44 μ g 3 times weekly (TIW) were less likely to have a relapse or activity on magnetic resonance imaging (MRI) compared with those who initiate therapy at a dosage of 30 μ g 1 time weekly (QW). Objective: To determine the effect of changing the dosage from 30 μ g QW to 44 μ g TIW in this extension of the EVIDENCE StudyDesign/Patients: Patients with relapsing MS originally randomized to interferon beta-1a, 30 μ g QW, during the comparative phase of the study changed to 44 μ g TIW, whereas patients originally randomized to 44 μ g TIW continued that regimen. Patients were followed up, on average, for an additional 32 weeks. Main Outcome Measure: The within-patient pretransition to posttransition change in relapse rate. Results: At the transition visit, 223 (73%) of 306 patients receiving 30 μ g QW converted to 44 μ g TIW, and 272 (91%) of 299 receiving 44-μ g TIW continued the same therapy. The posttransition annualized relapse rate decreased from 0.64 to 0.32 for patients increasing the dose (P<.001) and from 0.46 to 0.34 for patients continuing 44-μ g TIW (P =.03). The change was greater in those increasing dose and frequency (P=.047). Patients converting to the 44-μ g,TIW regimen had fewer active lesions on T2-weighted MRI compared with-before the transition (P=.02), whereas those continuing the 44-μ g TIW regimen had no significant change in T2 active lesions. Patients who converted to high-dose/high-frequency interferon beta-la therapy had increased rates of adverse events and treatment terminations consistent with the initiation of high-dose subcutaneous interferon therapy. Conclusions: Patients receiving interferon beta-la improved on clinical and MRI disease measures when they changed from 30μ g QW to 44 μ g TIW.
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