oru.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Gunnarsson, Martin
Publications (10 of 34) Show all publications
Forsberg, L., Kågström, S., Fält, A., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2019). A Swedish Nationwide study of the long-term effectiveness and safety of teriflunomid based on data from the Swedish "Immunomodulation and Multiple Sclerosis Epidemiology" Study (IMSE 4). Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 316-316
Open this publication in new window or tab >>A Swedish Nationwide study of the long-term effectiveness and safety of teriflunomid based on data from the Swedish "Immunomodulation and Multiple Sclerosis Epidemiology" Study (IMSE 4)
Show others...
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, no Suppl. 2, p. 316-316Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Teriflunomid (TFM) is a newly approved oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE) in order to track the long-term safety and effectiveness in a real-world setting.

Objectives: To track the long-term safety and effectiveness of TFM in a real-world setting.

Methods: A large majority of MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). The IMSE 4 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve.

Results: A total of 559 TFM-treated patients had been included in the IMSE 4 study from March 2014 to March 2019. 71 % were female and the mean age at treatment start was 46 years. The mean treatment duration was 23 months and 89 % of the patients had RRMS (9 % missing data on MS phenotype). Most patients switched from interferon/glatiramer acetate (36 %) and 16 % of the patients were treatment naïve before starting TFM. The overall one-year drug survival rate was 74 % and the overall two-year drug survival rate was 58 %. 232 (42 %) patients had terminated their treatment at some point, of which 46 % started rituximab treatment and 12 % had no new treatment registered. The most common reasons for discontinuation were AEs (41 %) and lack of effect (39 %). 229 patients had been continuously treated with TFM for ⩾24 months and significant changes in mean baseline values compared to values at 24 months were noted for EDSS (1.9 ± 1.5 to 2.1 ± 1.6, n=66) and SDMT (50.3 ± 10.5 to 52.3 ± 13.0, n=88). A total of 34 AEs were reported to the Swedish Medical Products Agency of which 9 events were classified as serious, none fatal.

Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. Patients starting TMF are older at treat-ment start than most other DMTs, which may explain the lack of improvement in EDSS scores. Still, a relatively high proportion switched due to lack of effect. A longer follow-up period is needed to assess the real-world effectiveness and safety of TMF.

Place, publisher, year, edition, pages
Sage Publications, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77225 (URN)000485303101202 ()
Conference
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved
Fält, A., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2019). A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (IMSE 3) for patients treated at least 24 months. Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 327-328
Open this publication in new window or tab >>A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (IMSE 3) for patients treated at least 24 months
Show others...
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, no Suppl. 2, p. 327-328Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Alemtuzumab (ALZ) is an approved disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) upon launch in Sweden (March 2014).

Objective: To track effectiveness and long-term safety of ALZ in a real-world setting.

Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes all patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS).

Results: A total of 118 MS patients (59% female; 95% RRMS) were included in IMSE 3 between March 2014 and April 2019. 95 patients had started ALZ >24 months ago (63% female; 98% RRMS) at cut-off date (31st of Mars 2019), where only 3 patients had switched to another DMT. Mean age at treatment start for patients treated at least 24 months was 34 years and mean treatment duration was 42 months. Mean number of drugs prior ALZ initiation was 2.3. Most patients (41/95) switched to ALZ from natalizumab, while 14/95 patients were treatment naïve with ALZ. The number of relapses per 1,000 patient years decreased from 471 before ALZ initiation to 65 during ALZ treatment (n=83, missing data; n=12). In patients treated ⩾ 24 months significant improvements in mean were seen for EDSS (1.9 ± 1.4 to 1.6 ± 1.3, n=57), MSSS (3.3 ± 2.6 to 2.4 ± 2.1, n=48) and EQ-5D (0.7 ± 0.3 to 0.8 ± 0.3, n=53), while MSIS-29, SDMT and VAS scores remained stable. A total of 28 adverse events were reported to the Swedish Medical Products Agency, 12 events were classified as serious and 16 events as non-serious. Two patients died during ALZ treatment, of which one patient died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.

Conclusions: Patients treated with ALZ for at least 24 months improved or remained stable across all effectiveness measures. Only a very small percentage of patients switched to other DMTs. Continued follow-up is needed to address long term effectiveness and safety of ALZ.

Place, publisher, year, edition, pages
Sage Publications, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77227 (URN)000485303101218 ()
Conference
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved
Fält, A., Kågström, S., Forsberg, L., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2019). A Swedish real word study of the long-term effectiveness and safety of fingolimod (IMSE 2) with focus on patients treated at least 48 months. Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 536-537
Open this publication in new window or tab >>A Swedish real word study of the long-term effectiveness and safety of fingolimod (IMSE 2) with focus on patients treated at least 48 months
Show others...
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, no Suppl. 2, p. 536-537Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Fingolimod (FGL) is an oral disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) introduced in Sweden 2011. Already from launch FGL was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) in order to enable long-term surveillance of effectiveness and safety aspects in a large population-based cohort.

Objective: To track the effectiveness and long-term safety of FGL in a real-world setting.

Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 2 includes patients starting FGL treatment and clinical and demographic data are collected from the NeuroReg. The Wilcoxon signed-rank test was used to assess changes in effectiveness measures.

Results: From September 2011 until April 2019, 1652 MS patients (67% female; 90% RRMS) were included in IMSE 2. Mean age at treatment start was 39 years and mean treatment duration in the entire cohort was 39 months. 608 patients (64% female; 91% RRMS) had been treated with FGL for at least 48 months with a mean age at treatment start of 40 years and a mean treatment duration of 70 months. A majority (330/608) switched to FGL from interferons/glatiramer acetate, while 194/608 switched from natalizumab. 105/608 patients had discontinued FGL at some point, mainly due to lack of effect (31%) and adverse events (31%). Most patients (57/105) switched to rituximab after FGL discontinuation. The number of relapses per 1,000 patient years were reduced from 275 before FGL initiation to 40 during FGL treatment (27% missing data). In patients treated with FGL at least 48 months significant changes (mean) were seen in Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT) and Visual Analogue Scale (VAS). 80/184 patients had a 4-point or 10% increase in SDMT score between baseline and 48 months. In total 167 adverse events were reported to the Swedish Medical Products Agency of which 77 events were classified as serious.

Conclusions: FGL displays a relatively high degree of drug persistence and clinical effectiveness is retained over time with significant improvements in MSSS, SDMT and VAS in patients treated at least 48 months. Furthermore, NeuroReg functions well as a drug surveillance platform, enabling monitoring of long-term effectiveness and safety.

Place, publisher, year, edition, pages
Sage Publications, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77231 (URN)000485303102194 ()
Conference
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Funder
The Swedish Brain FoundationSwedish Research Council
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved
Forsberg, L., Kågström, S., Fält, A., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2019). Clinical effectiveness of dimethyl fumarate with focus on patients treated at least 36 months - a Swedish nationwide study of the long-term effectiveness and safety of dimethyl fumarate (IMSE5). Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 316-317
Open this publication in new window or tab >>Clinical effectiveness of dimethyl fumarate with focus on patients treated at least 36 months - a Swedish nationwide study of the long-term effectiveness and safety of dimethyl fumarate (IMSE5)
Show others...
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, no Suppl. 2, p. 316-317Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).

Objective: To assess the effectiveness and safety of DMF with focus on patients treated at least 36 months in the IMSE study.

Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

Results: 2229 DMF-treated patients were included since March 2014 with a one- and two-year drug survival rate of 73% and 59%. The main reasons for discontinuation were AEs (51%) and lack of effect (29%). 77 AEs were reported to the Swedish Medical Products Agency of which 20 were serious. There were 6 fatal cases of which 4 were confirmed as unrelated to DMF and 2 were still under investigation.865 patients had continuous treatment for at least 36 months. This cohort had a mean age of 42 years and a mean treatment duration of 44 months. The majority had switched from interferon and glatiramer acetate (IFN&GA) (50%) or were treatment naïve (TN) (22%). Significant improvements in mean values at 36 months of treatment compared to baseline were noted for EDSS, MSSS, SDMT, MSIS-29 Psychological and EQ-5D. When TN patients were solely assessed improvements were noted for EDSS, MSSS, SDMT, MSIS-29 Physical and Psychological and EQ-5D. Treatment experienced patients displayed significant improvements only for MSSS and EQ-5D. Patients previously treated with IFN&GA also improved only in MSSS and EQ-5D. TN patients had a mean duration from diagnosis to treatment start of 6 months compared to 83 months for IFN&GA patients and 105 months for the remaining cohort.

Conclusions: DMF demonstrates clinical improvements in patients treated ⩾ 36 months, most pronounced in TN patients. However; the tolerability of DMF was reduced since 41% interrupted treatment during the first 24 months of therapy. Continued follow up is needed to assess the effectiveness and safety of DMF over longer time periods in a real world setting.

Place, publisher, year, edition, pages
Sage Publications, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77226 (URN)000485303101203 ()
Conference
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Funder
The Swedish Brain FoundationSwedish Research Council
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved
Granqvist, M., Burman, J., Gunnarsson, M., Lycke, J., Nilsson, P., Olsson, T., . . . Piehl, F. (2019). Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS. Multiple Sclerosis, Article ID 1352458519866600.
Open this publication in new window or tab >>Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS
Show others...
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, article id 1352458519866600Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited.

OBJECTIVE: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden.

METHODS:  We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016.

RESULTS: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p < 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p < 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p < 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p < 0.05 and p = 0.20, respectively).

CONCLUSION: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
Multiple sclerosis, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-beta, relapsing-remitting
National Category
Health Care Service and Management, Health Policy and Services and Health Economy Neurology
Identifiers
urn:nbn:se:oru:diva-75814 (URN)10.1177/1352458519866600 (DOI)000480888300001 ()31392923 (PubMedID)
Note

Funding Agency:

Neuroförbundet, Stockholms Läns Landsting and Vetenskapsrådet 

Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-08-29Bibliographically approved
de Flon, P., Laurell, K., Sundström, P., Blennow, K., Söderström, L., Zetterberg, H., . . . Svenningsson, A. (2019). Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial. Acta Neurologica Scandinavica, 139(5), 462-468
Open this publication in new window or tab >>Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial
Show others...
2019 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 5, p. 462-468Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis.

MATERIALS & METHODS: Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed for two years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed for an additional three years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA.

RESULTS: The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 (SD 393) to 354 (SD 174) pg/mL; p=0.006) and was statistically significant. The corresponding reduction in plasma-NFL was 18% (from 9.73 (SD 7.04) to 7.94 (SD 3.10) pg/mL; p=0.055) and did not reach statistical significance.

CONCLUSION: This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimise the use in clinical trials.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
Multiple sclerosis, cerebrospinal fluid, clinical trial, neurofilament light, plasma, rituximab, treatment
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-72477 (URN)10.1111/ane.13078 (DOI)000464338600008 ()30740668 (PubMedID)2-s2.0-85062548724 (Scopus ID)
Note

Funding Agencies:

County Council of Västerbotten  

County Council of Jämtland/Härjedalen  

County Council of Örebro  

Unit of Research, Education and Development, Region Jämtland Härjedalen  JLL-379731  JLL-649011  JLL 467731 

Syskonen Perssons Donationsfond  JLL-467381  JLL-652541 

Available from: 2019-02-14 Created: 2019-02-14 Last updated: 2019-06-18Bibliographically approved
Bridel, C., Gunnarsson, M. & Weiss, E. J. (2019). Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis. JAMA Neurology, 76(9), 1035-1048
Open this publication in new window or tab >>Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis
2019 (English)In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 76, no 9, p. 1035-1048Article, review/survey (Refereed) Published
Abstract [en]

Key Points: QuestionHow do levels of neurofilament light in cerebrospinal fluid (cNfL) compare between neurological conditions and with healthy controls?

Findings: Among 10 059 individuals in this systematic review and meta-analysis, cNfL was elevated in most neurological conditions compared with healthy controls, and the magnitude of the increase varies extensively. Although cNfL overlaps between most clinically similar conditions, its distribution did not overlap in frontotemporal dementia and other dementias or in Parkinson disease and atypical parkinsonian syndromes.

Meaning: The cNfL is a marker of neuronal damage and may be useful to differentiate some clinically similar conditions, such as frontotemporal dementia from Alzheimer disease and Parkinson disease from atypical parkinsonian syndromes.

This systematic review and meta-analysis assesses the associations of age, sex, and diagnosis with neurofilament light in cerebrospinal fluid and evaluates its potential in discriminating clinically similar conditions.

Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.

Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.

Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.

Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.

Data Extraction and Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.

Main Outcome and Measure: The cNfL levels adjusted for age and sex across diagnoses.

Results: Data were collected for 10059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n=2795), dementias and predementia stages (n=4284), parkinsonian disorders (n=984), and HC (n=1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.

Conclusions and Relevance: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77243 (URN)10.1001/jamaneurol.2019.1534 (DOI)000486895500008 ()31206160 (PubMedID)2-s2.0-85067362736 (Scopus ID)
Available from: 2019-10-14 Created: 2019-10-14 Last updated: 2019-10-14Bibliographically approved
Kågström, S., Fält, A., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2019). Improved clinical outcomes in patients treated with natalizumab for at least 8 years - real-world data from a Swedish national post-marketing surveillance study (IMSE 1). Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 763-764
Open this publication in new window or tab >>Improved clinical outcomes in patients treated with natalizumab for at least 8 years - real-world data from a Swedish national post-marketing surveillance study (IMSE 1)
Show others...
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, no Suppl. 2, p. 763-764Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).

Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.

Methods: In Sweden MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 1 includes patients starting NTZ treatment and data is collected from NeuroReg. Adverse events (AEs), JC-virus status (JCV) and clinical effec-tiveness measures are registered prospectively.

Results: A total of 3141 patients were included in the IMSE 1 study from August 2006 until April 2019 (72% female; men age 35 years; 79% RRMS; mean treatment duration 50 months) and 288 had been treated for at least 96 months. 71% of these 288 patients (71% female; men age 37 years; 82% RRMS; mean treatment duration 118 months) were treated with interferons and glatiramer acetate prior NTZ. At some point of time, 31% (90/288) discontin-ued NTZ treatment of which 41% discontinued due to JCV posi-tive (JCV+). In total, 30% (86/288) of these patients were JCV+with a mean JCV index of 1.2±1.0 (6% missing data). Relapses before treatment were reduced from 388/1000 patient years to 54 during treatment, 62% were relapse-free and 17% had 1 relapse during the entire treatment period (12% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT)) showed statistically significant improvement between baseline and 96 months. Over the entire observation time, 104 Serious AEs had been reported to the Swedish MPA and included 9 cases (2 fatal) of progressive multifocal leukoencephalopathy (PML) of which 8 between 2008 and 2012, and 1in 2018. 16 patients died during or within 6 months of last NTZ infusion. None were judged to be directly associated with NTZ.

Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding cognitive, physical and psychological measures, as well as relapse-control. Introduction of JCV testing has led to fewer treated JCV+ patients, which likely explains a drastic drop in the incidence of PML.

Place, publisher, year, edition, pages
Sage Publications, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77234 (URN)000485303103183 ()
Conference
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved
Luna, G., Alping, P., Burman, J., Fink, K., Fogdell-Hahn, A., Gunnarsson, M., . . . Frisell, T. (2019). Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurology
Open this publication in new window or tab >>Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies
Show others...
2019 (English)In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157Article in journal (Refereed) Epub ahead of print
Abstract [en]

Importance: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden.

Objective: To examine the risk of serious infections associated with disease-modifying treatments for MS.

Design, Setting, and Participants: This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included.

Exposures: Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA.

Main Outcomes and Measures: Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions.

Results: A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 [95% CI, 6.4-12.1] vs 5.2 [95% CI, 4.8-5.5] per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 [95% CI, 10.8-18.5] per 1000 person-years), natalizumab (incidence rate, 11.4 [95% CI, 8.3-15.3] per 1000 person-years), and rituximab (incidence rate, 19.7 [95% CI, 16.4-23.5] per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 [95% CI, 1.11-2.61]) but not fingolimod (HR, 1.30 [95% CI, 0.84-2.03]) or natalizumab (HR, 1.12 [95% CI, 0.71-1.77]) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 [1.34-2.46]) and fingolimod (HR, 1.71 [95% CI, 1.27-2.32]).

Conclusions and Relevance: Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.

Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77140 (URN)10.1001/jamaneurol.2019.3365 (DOI)31589278 (PubMedID)
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved
Biström, M., Hultdin, J., Andersen, O., Alonso-Magdalena, L., Jons, D., Gunnarsson, M., . . . Sundström, P. (2019). Leptin levels are associated with multiple sclerosis risk. Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 904-904
Open this publication in new window or tab >>Leptin levels are associated with multiple sclerosis risk
Show others...
2019 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, no Suppl. 2, p. 904-904Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Introduction: One environmental factor that in the last decade repeatedly has been linked to increased risk of developing multiple sclerosis (MS) is overweight, including obesity, early in life. The incidence of both MS and overweight are increasing, making elucidation of this connection important. The adipokine leptin is strongly correlated to both body mass index and total fat mass and the peptide hormone insulin is associated with obesity and type 2 diabetes, making leptin and insulin suitable biomarkers to investigate the connection between overweight and MS.

Objectives: To determine if leptin or insulin are risk factors for developing relapsing MS.

Aims: To further the understanding of how overweight influence MS risk.

Methods: In this case-control study, we compared concentrations of leptin and insulin in 649 individuals that later developed relapsing-remitting MS with 649 matched controls. Cases were matched for biobank, sex, date of sampling and age with decreasing priority. Only prospectively collected samples from individuals below the age of 40 were included in the study. Conditional logistic regression was performed on log10 transformed and z-scored values for the entire group, separately for men and women and divided into age groups.

Results: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals below 20 years of age (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.9) and for all men (OR 1.4, 95% CI 1.0–2.0). In contrast, for women aged 30-39 years there was a lower risk of MS with increased leptin levels (OR 0.74, 95% CI 0.54–1.0) when adjusting for insulin levels. No statistically significant association was found between insulin levels and MS risk.

Conclusions: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals. The age dependent relationship between leptin and MS risk in women - for whom leptin levels are several-fold higher than in men - suggests a possible role for leptin as being the link between MS risk and being overweight early in life.

Place, publisher, year, edition, pages
Sage Publications, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-77235 (URN)000485303104016 ()
Conference
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Funder
Swedish Research Council, 2015-02419
Available from: 2019-10-15 Created: 2019-10-15 Last updated: 2019-10-15Bibliographically approved
Organisations

Search in DiVA

Show all publications