BACKGROUND: COVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelinating disorders of the central nervous system and to determine disease exacerbation risk factors. METHODS: Data in this retrospective, observational cohort study was collected via the Czech nationwide registry ReMuS from March 1, 2020, to October 30, 2021. We compared the proportion of patients with at least one clinical relapse in the 90 days following vaccination or infection to the 90-day intervals during the year before. For the evaluation of the risk factors of relapse, a comparison between groups with and without relapses after COVID-19 vaccination or infection was made. RESULTS: We identified 1661 vaccinated (90.11% BNT162b2) patients with MS without a history of COVID-19 and 495 unvaccinated patients with MS who experienced COVID-19. A mild increase in the proportion of patients with at least one clinical relapse (-360 to -270 days: 4.46%; -270 to -180: 4.27%; -180 to -90: 3.85%; -90 to 0: 3.79% vs. 0 to +90 days: 5.30%) after vaccination in patients with MS was observed, as well as a rise in the proportion of patients with at least one clinical relapse after COVID-19. Lower age was associated with MS relapse after vaccination or infection. Although there were only 17 vaccinated and eight post-COVID-19 patients with NMOSD, the results were broadly consistent with those of patients with MS. CONCLUSION: There is a mild increase in the relapse incidence after the COVID-19 vaccination. The risks, however, need to be balanced against the risks of COVID-19 itself, also leading to the rise in relapse rate and particularly to morbidity and mortality.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- lidé MeSH
- neuromyelitis optica * komplikace MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- roztroušená skleróza * komplikace MeSH
- vakcína BNT162 MeSH
- vakcinace škodlivé účinky MeSH
- vakcíny proti COVID-19 * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND AND PURPOSE: Myasthenia gravis (MG) patients could be a vulnerable group in the pandemic era of coronavirus 2019 (COVID-19) mainly due to respiratory muscle weakness, older age and long-term immunosuppressive treatment. We aimed to define factors predicting the severity of COVID-19 in MG patients and risk of MG exacerbation during COVID-19. METHODS: We evaluated clinical features and outcomes after COVID-19 in 93 MG patients. RESULTS: Thirty-five patients (38%) had severe pneumonia and we recorded 10 deaths (11%) due to COVID-19. Higher forced vital capacity (FVC) values tested before COVID-19 were shown to be protective against severe infection (95% CI 0.934-0.98) as well as good control of MG measured by the quantified myasthenia gravis score (95% CI 1.047-1.232). Long-term chronic corticosteroid treatment worsened the course of COVID-19 in MG patients (95% CI 1.784-111.43) and this impact was positively associated with dosage (p = 0.005). Treatment using azathioprine (95% CI 0.448-2.935), mycophenolate mofetil (95% CI 0.91-12.515) and ciclosporin (95% CI 0.029-2.212) did not influence the course of COVID-19. MG patients treated with rituximab had a high risk of death caused by COVID-19 (95% CI 3.216-383.971). Exacerbation of MG during infection was relatively rare (15%) and was not caused by remdesivir, convalescent plasma or favipiravir (95% CI 0.885-10.87). CONCLUSIONS: As the most important predictors of severe COVID-19 in MG patients we identified unsatisfied condition of MG with lower FVC, previous long-term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment.
- MeSH
- azathioprin aplikace a dávkování MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- intravenózní imunoglobuliny terapeutické užití MeSH
- lidé MeSH
- myasthenia gravis * diagnostické zobrazování farmakoterapie chirurgie MeSH
- pyridostigmin-bromid aplikace a dávkování škodlivé účinky MeSH
- recidiva MeSH
- thymektomie MeSH
- vakcína proti hepatitidě A škodlivé účinky MeSH
- vakcína proti hepatitidě B škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Myasthenia gravis (MG) is the autoimmune disorder in which the thymus is considered the pathogenic organ. Thymectomy (TE) is a therapeutic option for MG and often ameliorates clinical symptoms. METHODS: We evaluated clinical features and outcomes after TE in patients without thymoma and the influence of TE with or without concomitant immunotherapy on the CD4(+)CD25(+) regulatory T cell subpopulation of lymphocytes in peripheral blood in defined followed groups of nonthymomatous MG patients. RESULTS: A total of 46 patients with generalized MG who underwent transsternal TE were identified. Neurologic outcomes after TE were favorable for the majority of patients mainly from the group treated with corticosteroids or combined immunosuppressive treatment. TEs with immunosuppressive treatment in MG patients were associated with increased percentages of CD4(+)CD25(+) cells (p<0.001). No significant change in the postoperative levels of CD4(+)CD25(+) cells was observed in thymectomized patients who preoperatively only received pyridostigmine. Also their clinical response to TE after 2 years of follow-up was worst of all followed groups. CONCLUSIONS: The exact mechanism by which TE ameliorates symptoms of MG is yet not clear. These observations indicate that increased percentages of CD4(+)CD25(+) T cells in MG may be related to disease stability and that TE and synergistic effect with concomitant, continuing immunotherapy augmented the proportion of CD4(+)CD25(+) T cells. On the basis of our observations TE alone is not enough to increase the number of circulating CD4(+)CD25(+) regulatory T cells and to establish complete stable remission.
- MeSH
- antigeny CD4 MeSH
- dospělí MeSH
- hodnocení výsledků zdravotní péče * MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- myasthenia gravis krev farmakoterapie chirurgie MeSH
- následné studie MeSH
- počet CD4 lymfocytů MeSH
- počet lymfocytů MeSH
- receptor interleukinu-2 - alfa-podjednotka MeSH
- regulační T-lymfocyty * MeSH
- thymektomie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- spasticita, fampridin PR, Sativex, tizanidin, Fampyra,
- MeSH
- 4-aminopyridin aplikace a dávkování farmakokinetika terapeutické užití MeSH
- baklofen aplikace a dávkování farmakokinetika terapeutické užití MeSH
- blokátory draslíkových kanálů aplikace a dávkování farmakologie terapeutické užití MeSH
- Cannabis MeSH
- chůze MeSH
- clonidin analogy a deriváty aplikace a dávkování farmakokinetika MeSH
- fixní kombinace léků MeSH
- kanabidiol aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kanabinoidy farmakologie škodlivé účinky terapeutické užití MeSH
- léky s prodlouženým účinkem MeSH
- lidé MeSH
- neurologické poruchy chůze farmakoterapie komplikace MeSH
- rostlinné extrakty MeSH
- roztroušená skleróza farmakoterapie komplikace MeSH
- svalová slabost MeSH
- svalová spasticita farmakoterapie komplikace MeSH
- tetrahydrokanabinol aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
Osoby s RS trpí øadou symptomù vèetnì bolesti, svalové spasticity a køeèí, obtíží s moèo- vým mìchýøem, poruchami spánku apod. Úleva tìchto symptomù zlepšuje kvalitu života pacientù s RS. Mnoho pacientù nemá dostateènou úlevu pøi standardní léèbì. Podáváme pøehled mechanizmu úèinku kanabinoidù v situaci zánìtu v CNS, jak je odvozen ze studií provedených u experimentální autoimunitní encefalomyelitidy, a pøehled studií u pacien- tù s RS, které zpùsobily registraci Sativexu v øadì zemí. Sativex je farmaceutický produkt vyrobený z konopí, urèený k léèbì spasticity a neuropatické bolesti u RS. Obsahuje Δ 9 -tet- rahydrokanabinol (THC) a kanabidiol (CBD) v pomìru 1:1. V nedávné dobì byly uskuteè- nìny 3 klinické studie se Sativexem. Léèba signifikantnì redukovala spasticitu (rezistentní vùèi standardní léèbì) a neuropatické bolesti u pacientù s pokroèilou RS, a to o 30 %. Odpovìï na léèbu pozorovaná bìhem prvních 4 týdnù je užiteèným nástrojem v predikci responzivity. Sativex byl registrován v ÈR 15. 4. 2011 pro léèbu spasticity u RS. .
People with MS suffer from a range of symptoms, including pain, muscle spasticity and spasm, bladder problems, sleep disturbance and other. Eleviating of these symptoms im- prove the quality of life. Many individuals with neuropathic pain and spasticity respond inadequately to current treatment options. We provide an overview of cannabinoid mode of action in the inflammed CNS as observed in experimental autoimmune encephalo- myelitis, and of studies in humans with MS which led to registration of Sativex in many countries Sativex ® is a cannabis-based pharmaceutical product for the treatment of spas- ticity and neuropathic pain due to multiple sclerosis, containing Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio. Recently three clinical trials were organized with Sativex. Sativex treatment resulted in a significant reduction in treatment-resistant spasticity and neuropatic pain in subjects with advanced MS. Treated patients improved by 30% compared to placebo. The response observed within the first 4 weeks of treatment appears to be a useful aid to predict responder/non-responder status. Sativex was registe- red in the Czech Republic as a treatment for spasticity in MS patients 15 Apr 2011
- Klíčová slova
- Sativex,
- MeSH
- Cannabis MeSH
- encefalomyelitida autoimunitní experimentální farmakoterapie MeSH
- kanabinoidy * farmakologie terapeutické užití MeSH
- lidé MeSH
- rostlinné extrakty terapeutické užití MeSH
- roztroušená skleróza * farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. METHODS: A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4weeks, after which those achieving an improvement in spasticity of ≥20% progressed to a 12-week randomized, placebo-controlled phase. RESULTS: Of the 572 subjects enrolled, 272 achieved a ≥20% improvement after 4weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of nabiximols (P=0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of nabiximols. CONCLUSIONS: The enriched study design provides a method of determining the efficacy and safety of nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment.
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- rostlinné extrakty terapeutické užití MeSH
- roztroušená skleróza komplikace farmakoterapie MeSH
- senioři MeSH
- svalová spasticita farmakoterapie etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
