Publications by authors named "Matthias Kant"

10 Publications

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Application of definitions for conversion to secondary progressive MS in a Danish nationwide population.

Mult Scler Relat Disord 2021 Oct 10;56:103319. Epub 2021 Oct 10.

The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark; Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: The number of patients with relapsing remitting multiple sclerosis (RRMS) who convert to secondary progressive (SP) MS is uncertain, and with emerging treatment options for SPMS, it is important to identify RRMS patients in transition to the SP phase. The objective of the present study was to characterize clinical parameters and use of disease modifying therapies in patients diagnosed with SPMS and RRMS patients already entered the SP phase by use of the Danish Multiple Sclerosis Registry (DMSR).

Methods: We used a cross-sectional design, including all living patients with MS as of June 30, 2020 from DMSR. First, we applied the MSBase definition of SPMS on all RRMS patients. Second, we applied the slightly modified inclusion criteria from the EXPAND clinical trial on patients with clinically confirmed SPMS and patients with RRMS fulfilling the MSBase definition of SPMS to identify SPMS patients recently progressed who may benefit from treatment with disease modifying therapy. We compared clinical characteristics and disease-modifying therapy use in the different patient groups.

Results: Among patients with clinically confirmed SPMS, application of a slightly modified EXPAND trial inclusion criteria for SPMS (m-EXPAND) captured patients who had converted to SPMS more recently and who had relapsed and initiated high-efficacy treatment more frequently. Moreover, our RRMS patients fulfilling the "SPMS"-criteria according to MSBase and recently progression according to m-EXPAND had similar characteristics and remarkably resembled the SPMS population in the EXPAND trial.

Conclusion: Our results indicate that data-driven diagnostic definitions might help identify RRMS patients at risk for SPMS and we highlight the challenges and reluctance in diagnosing SPMS in clinical practice.
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http://dx.doi.org/10.1016/j.msard.2021.103319DOI Listing
October 2021

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study.

Eur J Neurol 2021 Oct 13. Epub 2021 Oct 13.

The Danish Multiple Sclerosis Registry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Background And Purpose: Real-world evidence regarding the effectiveness and safety of ocrelizumab for the treatment of multiple sclerosis (MS) is limited. The aim was to evaluate the effectiveness and safety of ocrelizumab treatment for MS in a real-world setting.

Methods: A nationwide population-based cohort study was conducted where clinical and magnetic resonance imaging data of MS patients enrolled prospectively in the Danish Multiple Sclerosis Registry who initiated ocrelizumab treatment between January 2018 and November 2020 were analyzed.

Results: A total of 1104 patients (85.7% relapsing-remitting MS [RRMS], 8.8% secondary progressive MS [SPMS], 5.5% primary progressive MS [PPMS]) were included, with a median follow-up period of 1.3 years. At baseline, the mean age was 41.4 years in the RRMS group, 44.5 years in the PPMS group and 50.3 years in the SPMS group. Median Expanded Disability Status Scale score was 2.5, 3.5 and 5.5, respectively. Most RRMS and SPMS patients had received previous disease-modifying therapies (87.5% and 91.8%, respectively), whereas PPMS patients were mostly treatment naïve (78.7%). After ocrelizumab initiation, 9.3% of the patients experienced a relapse and 8.7% a 24 weeks confirmed disability worsening. Conversely, 16.7% showed a 24 weeks confirmed disability improvement. After ~1 year of treatment, most patients (94.5%) were free of magnetic resonance imaging activity. Ocrelizumab was generally well tolerated, as side effects were only reported for 10% of patients, mostly consisting of infusion-related reactions and infections.

Conclusions: It is shown that most MS patients treated with ocrelizumab are clinically stabilized and with an adverse event profile consistent with the experience from the pivotal clinical trials.
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http://dx.doi.org/10.1111/ene.15142DOI Listing
October 2021

Treatment Escalation vs Immediate Initiation of Highly Effective Treatment for Patients With Relapsing-Remitting Multiple Sclerosis: Data From 2 Different National Strategies.

JAMA Neurol 2021 Oct;78(10):1197-1204

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.

Importance: Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The difference in the association of these national strategies with clinical outcomes is unknown.

Objective: To investigate the association of national differences in disease-modifying treatment (DMT) strategies for RRMS with disability outcomes.

Design, Setting, And Participants: This cohort study used data on 4861 patients from the Danish and Swedish national multiple sclerosis (MS) registries from the date of index DMT initiation (between January 1, 2013, and December 31, 2016) until the last recorded visit at time of data extraction (October 2, 2019).

Exposures: All MS-specific DMTs initiated during the observation period were included in the analysis.

Main Outcomes And Measures: The primary study outcome was time to 24-week confirmed disability worsening. Secondary outcomes were 24-week confirmed disability improvement, milestone Expanded Disability Status Scale scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment switching. Data were analyzed using inverse probability of treatment weighting-based models using a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the 2 countries.

Results: A total of 2700 patients from the Swedish MS registry (1867 women [69.2%]; mean [SD] age, 36.1 [9.5] years) and 2161 patients from the Danish MS registry (1472 women [68.1%]; mean [SD] age, 37.3 [9.4 years]) started a first DMT between 2013 and 2016, were included in the analysis, and were observed for a mean (SD) of 4.1 (1.5) years. A total of 1994 Danish patients (92.3%) initiated a low to moderately effective DMT (teriflunomide, 907 [42.0%]) and 165 (7.6%) initiated a highly effective DMT, whereas a total of 1769 Swedish patients (65.5%) initiated a low to moderately effective DMT (teriflunomide, 64 [2.4%]) and 931 (34.5%) initiated a highly effective DMT. The Swedish treatment strategy was associated with a 29% reduction in the rate of postbaseline 24-week confirmed disability worsening relative to the Danish treatment strategy (hazard ratio, 0.71; 95% CI, 0.57-0.90; P = .004). The Swedish treatment strategy was also associated with a 24% reduction in the rate of reaching an expanded disability status scale score of 3 (hazard ratio, 0.76; 95% CI, 0.60-0.97; P = .03) and a 25% reduction in the rate of reaching an expanded disability status scale score of 4 (hazard ratio, 0.75; 95% CI, 0.61-0.96; P = .01) relative to Danish patients.

Conclusions And Relevance: The findings of this study suggest that there is an association between differences in treatment strategies for RRMS and disability outcomes at a national level. Escalation of treatment efficacy was inferior to using more efficacious DMT as initial treatment.
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http://dx.doi.org/10.1001/jamaneurol.2021.2738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369379PMC
October 2021

Real-world outcomes for a complete nationwide cohort of more than 3200 teriflunomide-treated multiple sclerosis patients in The Danish Multiple Sclerosis Registry.

PLoS One 2021 18;16(5):e0250820. Epub 2021 May 18.

The Danish Multiple Sclerosis Registry, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Objective: Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013-2019.

Methods: This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits.

Results: A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-naïve. Compared to previously treated patients, treatment-naïve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-naïve versus previously treated patients experienced a relapse during the follow-up (p<0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up.

Conclusions: Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250820PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130956PMC
November 2021

Alemtuzumab treatment in Denmark: A national study based on the Danish Multiple Sclerosis Registry.

Mult Scler 2021 Dec 29;27(14):2254-2266. Epub 2021 Mar 29.

Department of Neurology, Odense University Hospital, Odense, Denmark/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Objective: To investigate clinical outcomes in a real-world setting in the complete population-based cohort of alemtuzumab-treated MS patients in Denmark.

Methods: Data were retrieved from The Danish Multiple Sclerosis Registry between 2009 and 2019. Demographic and disease-specific patient parameters related to treatment history, efficacy, and safety outcomes were assessed at baseline and during follow-up visits.

Results: A total of 209 patients (78% female) started treatment with alemtuzumab during the study period with 3.1 ± 1.4 years follow-up. After 2 years, 75% of patients were relapse-free compared to 48% the year before alemtuzumab ( < 0.001). The annual number of relapses was reduced by 69% in year 4 compared with the year prior alemtuzumab. More active disease before alemtuzumab increased the annual hazard rate for relapse (HR: 2.88,  < 0.001). The Expanded Disability Status Scale (EDSS) score remained stable or improved in 81% of patients after 2 years. The need for an additional treatment course was associated with higher number of relapses in the year before alemtuzumab (odds ratio (OR) = 1.95,  = 0.001).

Conclusion: In a country with primarily escalation strategy, relapse rate reduction was maintained for 5 years, and EDSS stabilized/improved in majority of patients. Higher relapse rate 1 year before alemtuzumab increased the odds for additional courses. Novel serious AEs were not observed.
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http://dx.doi.org/10.1177/13524585211003291DOI Listing
December 2021

Initial high-efficacy disease-modifying therapy in multiple sclerosis: A nationwide cohort study.

Neurology 2020 08 7;95(8):e1041-e1051. Epub 2020 Jul 7.

From the Danish Multiple Sclerosis Registry (M.D.B., T.A.C., M.M.) and Danish Multiple Sclerosis Center (M.D.B., T.A.C., F.S., J.R.C., R.C., P.S.S., M.M.), Department of Neurology, Rigshospitalet; Department of Neurology (I.B., V.H., J.S.), Aalborg University Hospital; Department of Neurology (M.K.C., T.P., P.V.R.), Aarhus University Hospital; Department of Neurology (Z.I., V.P., Á.T.), Odense University Hospital; Brain and Nerve Diseases (H.B.J.), Lillebaelt Hospital, Kolding; Institute of Regional Health Research (H.B.J.), University of Southern Denmark, Odense; Department of Neurology (M.K.), Hospital of Southern Jutland, Sønderborg; and Department of Neurology (A.W.), Herlev Hospital, Denmark.

Objective: To determine the effectiveness of high-efficacy disease-modifying therapies (heDMTs) vs medium-efficacy disease-modifying therapies (meDMT) as the first treatment choice in treatment-naive patients with multiple sclerosis (MS) on disability worsening and relapses. We assessed this using a nationwide population-based MS registry.

Methods: We identified all patients starting a heDMT as first-time treatment from the Danish Multiple Sclerosis Registry and compared treatment outcomes with a propensity score matched sample of patients starting meDMT.

Results: We included 388 patients in the study: 194 starting initial therapy with heDMT matched to 194 patients starting meDMT. At 4 years of follow-up, the probabilities of a 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening were 16.7% (95% confidence interval [CI] 10.4%-23.0%) and 30.1% (95% CI 23.1%-37.1%) for heDMT and meDMT initiators, respectively (hazard ratio [HR] 0.53, 95% CI 0.33-0.83, = 0.006). Patients initiating heDMT also had a lower probability of a first relapse (HR 0.50, 95% CI 0.37-0.67). Results were similar after pairwise censoring and in subgroups with high baseline activity, diagnosis after 2006, or information on baseline T2 lesion load.

Conclusion: We found a lower probability of 6-month confirmed EDSS score worsening and lower probability of a first relapse in patients starting a heDMT as first therapy, compared to a matched sample starting meDMT.

Classification Of Evidence: This study provides Class III evidence that for patients with MS, starting heDMT lowers the risk of EDSS worsening and relapses compared to starting meDMT.
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http://dx.doi.org/10.1212/WNL.0000000000010135DOI Listing
August 2020

Comparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort study.

Neurology 2019 04 15;92(16):e1811-e1820. Epub 2019 Mar 15.

From the Danish Multiple Sclerosis Center (M.D.B., T.A.C., F.S., P.S.S., M.M.), Rigshospitalet; Copenhagen University Hospital Rigshospitalet (J.F., H.H.-K.-R.), Glostrup; Slagelse Hospital (M.K.G.); Odense University Hospital (Z.I., T.S.), University of Southern Denmark; Hospital of Southern Jutland (M.K.), Sønderborg; Aalborg University Hospital (Z.M.); Aarhus University Hospital (T.P., P.V.R.); Greater Copenhagen Hospitals-NOH (H.R.), Hillerød; University Hospital of Sjaelland (A.T.), Roskilde; and Department of Neurology, Copenhagen University Hospital Herlev (A.W.), Denmark.

Objective: To compare on-treatment efficacy and discontinuation outcomes in teriflunomide (TFL) and dimethyl fumarate (DMF) in the treatment of relapsing-remitting multiple sclerosis (RRMS) in a real-world setting.

Methods: We identified all patients starting TFL or DMF from the Danish Multiple Sclerosis Registry and compared on-treatment efficacy outcomes between DMF using TFL, adjusted for clinical baseline variables and propensity score-based methods.

Results: We included 2,236 patients in the study: 1,469 patients on TFL and 767 on DMF. Annualized relapse rates (ARRs) in TFL and DMF were 0.16 (95% confidence interval [CI] 0.13-0.20) and 0.09 (95% CI 0.07-0.12), respectively. Relapse rate ratio for DMF/TFL was 0.58 (95% CI 0.46-0.73, < 0.001). DMF had a higher relapse-free survival proportion at 48 months of follow-up ( < 0.05). We observed no difference in Expanded Disability Status Scale score worsening. Discontinuations due to disease breakthrough were 10.2% (95% CI 7.6%-12.8%) and 22.1% (95% CI 19.2%-25.0%) for DMF and TFL, respectively. A subgroup analysis of ARRs in 708 patients with available baseline MRI T2 lesion amount reported similar results after adjustment.

Conclusion: We found lower ARR, higher relapse-free survival, and lower incidence of discontinuation due to disease breakthrough on treatment with DMF compared with TFL.

Classification Of Evidence: This study provides Class II evidence that for patients with RRMS, DMF is more effective in preventing relapses and has lower discontinuation due to disease breakthrough compared with TFL.
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http://dx.doi.org/10.1212/WNL.0000000000007314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550503PMC
April 2019

Nationwide prevalence and incidence study of neuromyelitis optica spectrum disorder in Denmark.

Neurology 2018 12 9;91(24):e2265-e2275. Epub 2018 Nov 9.

From the Department of Neurology (V.P., K.S., T.P.), Aarhus University Hospital; Department of Neurology (Z.I., H.H.N.), Odense University Hospital; Institute of Clinical Research (Z.I., H.H.N.), Institute of Molecular Biology (H.H.N.), and Department of Regional Health Research, Faculty of Health Sciences (E.S.), University of Southern Denmark, Odense; The Danish Multiple Sclerosis Center (M.M., P.E.H.J., F.S.), Department of Neurology, Rigshospitalet, University of Copenhagen; The Danish Multiple Sclerosis Registry (M.M., N.K.-H.), Department of Neurology, Rigshospitalet, Copenhagen University Hospital; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), and Department of Biomedicine (T.C.), Aarhus University; MS-Clinic of Southern Jutland (Sønderborg, Esbjerg, Kolding) (M.K., E.S.), Department of Neurology, Hospital of Southern Jutland, Sønderborg; Department of Neurology (C.C.P., Z.M.), Aalborg University Hospital; Multiple Sclerosis Unit (S.F.R.), Department of Neurology, Herlev Hospital, Copenhagen; Department of Neurology (M.B.J.), Nordsjællands Hospital, Hillerød; Department of Neurology (A.E.P.), Hospital of Southwest Jutland, Esbjerg; Department of Neurology (L.R.), Hospital of Central Denmark Region, Viborg; Department of Autoimmunology and Biomarkers (M.C.L., N.H.), Statens Serum Institut, Copenhagen; and Department of Neurology (J.L.F.), Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark.

Objectives: To estimate the nationwide population-based incidence, prevalence, and geographical distribution of neuromyelitis optica (NMO) spectrum disorder (NMOSD) in Denmark based on the 2015 International Panel for NMO Diagnosis (IPND) criteria.

Methods: We conducted a multicentre, historically prospective study. Data were sourced from the Danish National Patient Registry, the Danish Multiple Sclerosis Registry, departments of neurology, and laboratories providing aquaporin-4 antibody test. Cases were selected based on the 2006 Wingerchuk and the 2015 IPND criteria and were individually validated by an expert panel.

Results: We confirmed NMO in 30 cases (2006 criteria) and NMOSD in 56 cases (2015 IPND criteria) between 2007 and 2014. Defined by the 2006 criteria, the incidence of NMO was 0.029 per 100,000 person-years (95% confidence interval [CI] 0.014-0.051), and the prevalence (aged 16 years and older) was 0.566 per 100,000 (95% CI 0.370-0.830). Based on the 2015 IPND criteria, the incidence of NMOSD was 0.070 per 100,000 person-years (95% CI 0.046-0.102), and the prevalence (aged 16 years and older) was 1.09 per 100,000 (95% CI 0.808-1.440), without regional differences.

Conclusions: Our estimates of incidence and prevalence are similar to other Caucasian population-based studies using the 2015 IPND criteria. We found no geographical clustering in Denmark.
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http://dx.doi.org/10.1212/WNL.0000000000006645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329324PMC
December 2018

High treatment adherence, satisfaction, motivation, and health-related quality of life with fingolimod in patients with relapsing-remitting multiple sclerosis - results from a 24-month, multicenter, open-label Danish study.

Patient Prefer Adherence 2018 29;12:1139-1150. Epub 2018 Jun 29.

Department of Child and Adolescent Health, Aarhus University Hospital Skejby, Aarhus Denmark.

Purpose: Treatment adherence is a prerequisite for treatment success and therefore an important consideration to assure that therapeutic goals are achieved both from a patient point of view and for optimal health care resource utilization. Published data on treatment adherence with fingolimod (Gilenya) are limited. Therefore, this study investigated treatment adherence in patients with relapsing-remitting multiple sclerosis (RRMS) treated with fingolimod in Denmark.

Patients And Methods: This was a 24-month, multicenter, open-label study, investigating treatment adherence, satisfaction, motivation, and health-related quality of life (QoL) in RRMS patients treated with fingolimod. In addition, the effect of a motivational interview support program on these measures was evaluated. Treatment adherence was assessed by pill count. Treatment satisfaction, motivation, and QoL were assessed by patient-reported outcomes (PROs).

Results: A total of 195 patients were enrolled in the study. A very high treatment adherence was observed during the entire study with no statistically significant difference between study visits before (99%) and after (97%) the motivational interview. In accordance, a high level of treatment satisfaction was found in the Treatment Satisfaction Questionnaire for Medication 9, which was scored high throughout the study with the highest scores seen for the convenience domain (ranging from 94.51 to 95.78). Furthermore, additional PROs demonstrated a high health-related QoL, a self-determined form of motivation for taking medication, and a patient perception of an autonomy supportive approach provided by the health care provider, at all study visits.

Conclusion: High levels of treatment adherence, satisfaction, motivation, and QoL were observed in Danish RRMS patients treated with fingolimod. As these positive measures were observed at all study visits and throughout the study, no effect of the motivational interview support program was found.
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http://dx.doi.org/10.2147/PPA.S166278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029605PMC
June 2018

Differences between users and non-users of complementary and alternative medicine among people with multiple sclerosis in Denmark: a comparison of descriptive characteristics.

Scand J Public Health 2013 Jul 2;41(5):492-9. Epub 2013 Apr 2.

Department of Public Health, University of Copenhagen, Denmark. [email protected] scleroseforeningen.dk

Aims: The aim of this study was to investigate differences in socio-economic characteristics between CAM users and CAM non-users among people with MS in Denmark as well as differences in characteristics related to the use of CAM among CAM users and the use of conventional treatments among CAM non-users.

Methods: An internet-based questionnaire was used to collect data from 3361 patient members of the Danish MS society. A letter with a personal code was sent to all respondents, asking them to fill out the questionnaire online. Reminders to non-respondents were sent twice and the final response rate was 55.5%. Statistical associations were presented as odds ratios and with respective 95% confidence intervals.

Results: People with MS in Denmark use a wide range of CAM treatments for a variety of reasons. CAM users were more likely to be of female gender, 18-40 years of age, educated at bachelor level or above, and have a high income compared to CAM non-users (p < 0.05). CAM users more often addressed non-specific/preventive treatment purposes through their use of CAM treatments, they communicated less often with a medical doctor about the CAM treatments used, and they experienced less side effects as well as less positive effects from the CAM treatments used when compared with the use of conventional treatments among CAM non-users (p < 0.05).

Conclusions: People with MS in Denmark reported use of a large range of CAM treatments. CAM users differed from CAN non-users in relation to socio-economic factors as well as treatment characteristics.
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http://dx.doi.org/10.1177/1403494813481646DOI Listing
July 2013
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