| 1. |
|
|
| 2. |
|
|
| 3. |
- Kuhle, J., et al.
(författare)
-
Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
- 2015
-
Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Kuhle, J, et al.
(författare)
-
A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis
- 2016
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 22:4, s. 533-543
-
Tidskriftsartikel (refereegranskat)abstract
- To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). Methods: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. Results: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R2: 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited ( R2: 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. Conclusions: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.
|
|
| 7. |
|
|
| 8. |
- Flachenecker, P, et al.
(författare)
-
Multiple sclerosis registries in Europe - results of a systematic survey
- 2014
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:11, s. 1523-1532
-
Tidskriftsartikel (refereegranskat)abstract
- Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. Methods: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries’ leaders, followed by telephone interviews with them. Results: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology ( n=10), long-term therapy outcome ( n=8), healthcare research ( n=9) and support/basis for clinical trials ( n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients’ perspectives were only collected in six registries. Conclusions: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Miller, AE, et al.
(författare)
-
Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis
- 2012
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 18:11, s. 1625-1632
-
Tidskriftsartikel (refereegranskat)abstract
- The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients. Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups. Methods: RMS patients ( n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks. Subgroup analyses were performed for ARR and disability progression by baseline demographics (gender, race, age), disease characteristics (Expanded Disability Status Scale (EDSS) strata, relapse history, multiple sclerosis (MS) subtype), MRI parameters (gadolinium-enhancing lesions, total lesion volume) and prior use of MS drugs. A generalized estimating equation method and Cox regression model were used to assess consistency of the treatment effect across subgroups, utilizing a treatment-by-subgroup interaction test for each factor separately. Results: Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide, with no treatment-by-subgroup interaction test reaching statistical significance. Conclusion: The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
