| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Jons, D., et al.
(författare)
-
Increase in Epstein Barr virus serologies precedes neuroaxonal damage in pre-symptomatic multiple sclerosis
- 2022
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 86-87
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Epstein-Barr virus (EBV) infection may be a pre-condition for the development of multiple sclerosis (MS). EBV antibodies, predominantly anti-EBNA1, develop in the presymp-tomatic phase of virtually all MS patients. Using material from a serum repository, studies in advance of MS onset indicated that EBV seropositivity preceded the first expression of incipient axonal lesions, serum Neurofilament Light (sNFL) .Objectives: To determine the onset and individual order of appearance of EBV seroreactivity and the serum neuroaxonal injury marker neurofilament light (sNfL) in a wide age spectrum of presymptomatic MS patients.Aims: To characterize the presymptomatic appearance of anti-bodies against an intranuclear (EBNA1) and a surface EBV anti-gen (gp350) and sNfL.Methods: A nested case-control study in 669 pre-symptomati-cally acquired blood samples from persons who later received an MS diagnosis, and from 1:1 matched control persons. Serum lev-els of EBNA1, VCA and gp350 IgG antibodies and sNFL (n=519) were measured in individual presymptomatic samples and expressed as delta scores with matched controls in relation to time until MS onset.Results: Serum levels expressed as delta scores for anti EBV and NfL IgG showed an incipient increase for anti EBNA1 and gp350 from 15-20 years before MS debut. Significant (p=0.001 and p=0.002) from 10-15 years, with consistent delta-scores succes-sively closer to MS onset. These findings contrasted to the level of sNfL which increasingly diverged from matched controls from 5-10 years before the onset of MS. None of the individual sam-ples negative for both EBNA1 and VCA IgG antibodies in the pre-MS group (n = 36) showed any elevation of the sNfL level.Conclusions: In a pre-MS material, the seroreactivity against EBNA1 was followed by VCA and gp350, before increased sNFL appeared, indicating incipient axonal injury. Together with its biological characteristics this temporal order confirms the role of EBV as a trigger of MS.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Alping, P., et al.
(författare)
-
Effectiveness of initial MS treatments in the COMBAT-MS trial : injectables, dimethyl fumarate, natalizumab and rituximab
- 2021
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 21-22
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Direct comparisons across multiple disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) are valuable in clinical decision making. COMBAT-MS (NCT03193866) is an observational drug trial capturing data on clinical relapses, lesions on magnetic resonance imaging (MRI), Expanded Disability Status Scale (EDSS), and drug survival, at all Swedish university clinics.Objective: Compare the effectiveness of the most common initial MS therapies in Sweden.Methods: All first-ever MS treatments with injectables (INJ, interferon-β/glatiramer acetate), dimethyl fumarate (DMF), natalizumab (NTZ), and rituximab (RTX), started 2011-01-01 to 2020-12-14, were identified with prospectively recorded outcome data in the Swedish MS Register. Follow-up continued even if the therapy ended. Missing data were imputed using multiple imputation and potential confounding was adjusted for using stabilized inverse probability of treatment weighting with baseline variables: age, sex, MS duration, geographical region, EDSS, and relapses. All comparisons are made against RTX.Results: We included 1936 first-ever therapy episodes: 856 INJ, 341 DMF, 270 NTZ, and 469 RTX. Baseline characteristics differed by DMT, with natalizumab having the youngest patients, shortest MS duration, and the most previous relapses.After adjustment, the hazard ratio (HR) for first relapse vs RTX was for INJ 5.9 (95% confidence interval 3.7; 9.5), DMF 2.8 (1.7; 4.8), and NTZ 1.8 (1.0; 3.3). Similarly, the relative three-year lesion rate was for INJ 6.06 (3.75; 9.80), DMF 3.52 (2.01; 6.17), and NTZ 2.03 (1.14; 3.64). EDSS differences at three years were only marginally different: INJ 0.25 (0.06; 0.44), DMF 0.05 (-0.16; 0.26), and NTZ 0.00 (-0.23; 0.24). In contrast, HR for treatment discontinuation was marked: INJ 32.5 (19.0; 55.7), DMF 20.2 (11.5; 35.4), and NTZ 16.2 (8.9; 29.5).Conclusions: In treatment-naïve patients, RTX was associated with the lowest risk of relapses and MRI lesions, and by far the lowest probability of switching to a second therapy. In contrast, EDSS at 3 years was similar for RTX, DMF, and NTZ, and only slightly higher for INJ. The apparent difference in effectiveness between NTZ and RTX could possibly be explained by the vulnerable period after switching from NTZ, mainly due to JC virus positivity. These findings underscore the importance of tracking long-term outcomes from first DMT start, while considering subsequent therapy switches.
|
|
