Objective
In patients suffering multiple sclerosis activity despite treatment with interferon β or glatiramer acetate, clinicians often switch therapy to either natalizumab or fingolimod. However, no ...studies have directly compared the outcomes of switching to either of these agents.
Methods
Using MSBase, a large international, observational, prospectively acquired cohort study, we identified patients with relapsing–remitting multiple sclerosis experiencing relapses or disability progression within the 6 months immediately preceding switch to either natalizumab or fingolimod. Quasi‐randomization with propensity score–based matching was used to select subpopulations with comparable baseline characteristics. Relapse and disability outcomes were compared in paired, pairwise‐censored analyses.
Results
Of the 792 included patients, 578 patients were matched (natalizumab, n = 407; fingolimod, n = 171). Mean on‐study follow‐up was 12 months. The annualized relapse rates decreased from 1.5 to 0.2 on natalizumab and from 1.3 to 0.4 on fingolimod, with 50% relative postswitch difference in relapse hazard (p = 0.002). A 2.8 times higher rate of sustained disability regression was observed after the switch to natalizumab in comparison to fingolimod (p < 0.001). No difference in the rate of sustained disability progression events was observed between the groups. The change in overall disability burden (quantified as area under the disability–time curve) differed between natalizumab and fingolimod (−0.12 vs 0.04 per year, respectively, p < 0.001).
Interpretation
This study suggests that in active multiple sclerosis during treatment with injectable disease‐modifying therapies, switching to natalizumab is more effective than switching to fingolimod in reducing relapse rate and short‐term disability burden. Ann Neurol 2015;77:425–435
At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and ...burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. However, evidence from clinical trials is generally lacking, particularly regarding sequencing, switches and escalation of drugs. Also, there is a need to identify patients who require highly efficacious treatment from the onset of their disease to prevent deterioration. The recently published European Committee for the Treatment and Research in Multiple Sclerosis/European Academy of Neurology clinical practice guidelines on pharmacological management of MS cover aspects such as treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and are based on expert consensus statements. However, the recommendations constitute an excellent framework that should be adapted to local regulations, MS center capacities and infrastructure. Further, available and emerging biomarkers for treatment guidance were discussed. Magnetic resonance imaging parameters are deemed most reliable at present, even though complex assessment including clinical evaluation and laboratory parameters besides imaging is necessary in clinical routine. Neurofilament-light chain levels appear to represent the current most promising non-imaging biomarker. Other immunological data, including issues of immunosenescence, will play an increasingly important role for future treatment algorithms. Cognitive impairment has been recognized as a major contribution to MS disease burden. Regular evaluation of cognitive function is recommended in MS patients, although no specific disease-modifying treatment has been defined to date. Finally, systematic documentation of real-life data is recognized as a great opportunity to tackle unresolved daily routine challenges, such as use of sequential therapies, but requires joint efforts across clinics, governments and pharmaceutical companies.
Abstract Although myasthenia gravis (MG) has long been considered a well-established autoimmune disease associated with autoantibodies, which are convincingly pathogenic, accumulating data indicate ...both clinical and biological heterogeneity similar to many other putative autoimmune disorders. In a subset of patients, thymus plays a definite role: thymic autoimmunity results in generation of autoantibodies within the thymus, which cross-react with antigens at the neuromuscular junction, or thymoma leads to deficient central tolerance and impaired T cell selection. Heterogeneity on the autoantibody level may be associated with genetic heterogeneity and clinical phenotypes with different treatment responses.
Multiple sclerosis (MS) experts in Europe are facing rapidly rising demands of excellence due to the increasing complexity of MS therapy and management. A central European expert board of MS experts ...met to identify needs and obstacles with respect to raising quality of MS care in central and Eastern European countries. There are substantial variations across countries regarding delivery of care and its cost structure, as well as access to treatment. To date, Eastern European countries are often less able to afford reimbursement of immunomodulatory agents than Western countries. Overall, approximately 40% of working-age patients are not working due to MS. Costs rise steeply with increasing disability; indirect costs constitute the bulk of the financial burden in patients with severe MS. Magnetic resonance imaging (MRI) assessment is meanwhile obligatory as the diagnostic interface in the management of MS patients. Recommended measures directed at improving quality of care include the collection of patient data in registries, enhanced education of healthcare professionals, implementation of national strategies aiming at reducing regional variation, optimization of approval processes, and removal of administrative barriers. Local partnerships with authorities such as those that represent the interests of employees can contribute to leverage the importance of epidemiological data. The need for education extends to (neuro)radiologists who are responsible for reporting MRI findings in expert quality. Dissemination of the Magnetic Resonance Imaging in MS (MAGNIMS) protocol would be an important step in this context. Also, clinical freedom of choice is rated as essential. Physicians should have access to a range of treatment options due to the complexity of disease. Guidelines such as the upcoming EAN-ECTRIMS clinical practice guideline also aim at providing a basis for argumentation in negotiations with national health authorities.
Fingolimod was approved and reimbursed by the healthcare provider in Hungary for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS) in 2012. The present study aimed to ...assess the effectiveness, safety profile, and persistence to fingolimod in a real-life setting in Hungary in RRMS patients who were either therapy naïve before enrollment or have changed to fingolimod from another disease-modifying therapy (DMT) for any reason.
This cross-sectional, observational study with prospective data collection was performed nationwide at 21 sites across Hungary. To avoid selection bias, sites were asked to document eligible patients in consecutive chronological order. Demographic, clinical, safety and efficacy data were analysed for up to 5 years from 570 consenting adult patients with RRMS who had received treatment with fingolimod for at least one year.
69.6% of patients remained free from relapses for the whole study duration; in the first year, 85.1% of patients did not experience a relapse, which rose to 94.6% seen in the 5th year. Compared to baseline at study end, 28.2% had higher, and 9.1% had lower, meanwhile, 62.7% of the patients had stable EDSS scores. Overall, the annualized relapse rate decreased from 0.804 observed at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (77.0%, 82.1%, 85.2%, 89.7%, and 89.0% relative reduction, respectively) after 1, 2, 3, 4, and 5 years of treatment. The greatest reduction rate was seen in the group of therapy naïve patients. Treatment persistence on fingolimod after 60 months was 73.4%.
In this nationwide Hungarian cohort, most patients under fingolimod treatment were free from relapses and disability progression. In addition, fingolimod has proven to be a well-tolerated DMT that has sustained its manageable safety profile, high efficacy, and positive benefit/risk ratio for up to 5 years in a real-life setting.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Health‐related quality of life (HRQoL) is lower in people with multiple sclerosis (PwMS) compared to the healthy population, psychological symptoms accompanying multiple sclerosis (MS) ...have a serious impact on the HRQoL of PwMS. Data regarding the subject, however, remain conflicting.
Objectives
To evaluate the patients' sociodemographic attributes, education, fatigue, depression, and cognitive impairment level of impact on the HRQoL for the whole cohort as well as comparing the sexes.
Materials and Methods
Three hundred and twenty‐two relapse‐remitting MS patients filled out the Fatigue Impact Scale (FIS), Beck Depression Inventory (BDI), MS Quality of Life‐54 (MSQoL‐54) questionnaires, cognitive impairment were identified using Brief International Cognitive Assessment for MS (BICAMS) test. The patients' data were acquired from our clinic's MS registry or from patients' files.
Results
Depression and fatigue were found to have the most ubiquitous and robust effect on the overall and any given subdivision of the HRQoL composite. Other factors had a slight effect on some of the subscales when the whole cohort was evaluated. When the genders were compared, differences were found on 10 domains.
Conclusion
Psychopathological symptoms have a more powerful influence on the HRQoL of MS patients than physical impairment, also these symptoms influence men's and women's HRQoL with different power. This invokes the need for complex and personalized care in the treatment of PwMS. Ours is the first study to show a difference between the sexes in this regard.
The determining factors of the health‐related quality of life of MS patients were assessed. Psychopathological, not physical symptoms were found to be the main influencers of one's health‐related quality of life (HRQoL). Also a difference between men and women was found regarding which factors determine a patient's HRQoL and the power of influence a given factor has on one's HRQoL.
Multiple sclerosis (MS) may impact quality of life, careers and family plans of the affected individuals. The current treatments with disease modifying therapies aim to prevent people with MS (pwMS) ...from disability accumulation and progression. Different countries have different reimbursement policies resulting in inequalities in patient care among geographical regions. Access to anti-CD20 therapies for relapsing MS is restricted in Hungary because therapy of individual cases only is reimbursed. In the light of the latest research and national guidelines, 17 Hungarian MS experts agreed on 8 recommendations regarding relapsing pwMS using the Delphi round method. Strong agreement (> 80%) was achieved in all except one recommendation after three rounds, which generated a fourth Delphi round. The experts agreed on treatment initiation, switch, follow-up and discontinuation, as well as on special issues such as pregnancy, lactation, elderly population, and vaccination. Well-defined national consensus protocols may facilitate dialogue between policymakers and healthcare professionals and thus contribute to better patient care in the long run.
Acute mortality rate of stroke in Hungary is significantly higher than in Western Europe, which is likely to be partially attributable to suboptimal treatment.
We examined the use of acute vascular ...imaging and mechanical thrombectomy for acute ischaemic stroke patients. We collected data on 20 consecutive patients from Hungarian stroke centers before 31st August 2016.
Out of the reported 410 patients, 166 (40.4%) underwent CT angiography and 44 (10.7%) had mechanical thrombectomy.
Only about 1/3 of acute ischaemic stroke patients eligible for thrombectomy actually had it. The underlying reasons include long onset-to-door time, low utilization of acute vessel imaging and a limited neuro-intervention capacity needing improvement.
Cognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS); its prevalence is reported to be 43–70%. It is one of the most important determinants of MS patients’ quality of life, as ...it is one of the main factors for MS patients becoming unemployed.
We aimed to determine the prevalence of CI among the relapsing-remitting MS (RRMS) and clinically isolated syndrome (CIS) patients in Hungary, to evaluate the predicting factors of CI and to assess the differences between sexes and patients with different educational levels.
Five-hundred and fifty-three CIS and RRMS patients were enrolled to our study from three Hungarian MS centers. Age at screening, age at disease onset, disease duration, EDSS score, sex and educational levels were analyzed as socio-demographic factors. The BICAMS battery was used to assess their cognitive state, the BDI-II battery to assess depression. For statistical analysis, we utilized logistical regression, and used Fisher exact tests, chi-square tests and one-way ANOVA.
The mean age of our patients was 44.93 ± 11.69 years, mean age at disease onset was 31.95 ± 10.01 years, the mean disease duration was 13.05 ± 8.05 years and the median EDSS score 2.0 (Range: 6.5, IQR:2.0) points. Three-hundred and sixteen (57.1%) patients had CI. Sex, educational level and EDSS score proved to be significant predictors of CI (OR: 2.71, p < 0.001; OR: 1.94, p = 0.023; OR: 0.47, p = 0.003 respectively). CI was significantly (p < 0.001) more frequent among men (70.1%) than women (52.0%). We found, that educational level and EDSS score were only a significant predicting factor among women. Thus, the prevalence of CI among women with college or university degree was significantly (p < 0.001) less common (39.4%) than women with 12–15 years of education (57.4%) and women without a high school degree (66.7%). Also, we found that among women with higher EDSS score than 2 points, the prevalence of CI is 69.9% as compared to women with EDSS score between 0 and 2 points, where the prevalence is 42.8% (p < 0.001). No such differences were observed among man.
Our prevalence data is similar to those reported in the literature (43–70%), and almost identical to the one assessment using the BICAMS battery. We found that men are more vulnerable to CI than women in MS, as was reported recently. We are the first to report however, that higher educational level and lower EDSS scores are only associated with better cognitive performance in women.
•57.2% of the patients have cognitive impairment on some level.•The most affected cognitive area is the information processing speed.•Men are more susceptible for cognitive impairment (70.1%) than women (51.6%).•Educational level does not have an impact on cognitive dysfunction among men, but higher educational level is a protective factor among women.
Abstract Using the emerging technique of peripheral nerve ultrasonography, multiple focal nerve swellings corresponding to sites of existing conduction blocks have been described in demyelinating ...polyneuropathies. We report two cases of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). In the first, multiple focal nerve enlargements were detected by ultrasound at sites of previous conduction blocks, well after complete clinical and electrophysiological resolution. In the second case, existing proximal conduction blocks could be localized by ultrasound. Our cases highlight the importance of nerve ultrasound in identifying conduction blocks and demonstrate that ultrasonographic morphological changes may outlast functional recovery in demyelinating neuropathies.
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