Total drug treatment and comorbidity in myasthenia gravis: a population-based cohort study.
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ABSTRACT:
SUBMITTER: Andersen JB
PROVIDER: S-EPMC4238850 | biostudies-other | 2014 Jul
REPOSITORIES: biostudies-other
Publications
Total drug treatment and comorbidity in myasthenia gravis: a population-based cohort study.
Andersen J B JB Owe J F JF Engeland A A Gilhus N E NE
European journal of neurology 20140409 7
<h4>Background and purpose</h4>Comorbidity in myasthenia gravis (MG) is important for diagnosis, treatment and prognosis. Disease complexity was assessed by examining total drug treatment, immune therapy and comorbidity in a complete national MG cohort.<h4>Methods</h4>All recipients of the MG-specific drug pyridostigmine 2004-2010 registered in the compulsory Norwegian Prescription Database who met the inclusion criteria were included. The pyridostigmine group was compared with the general Norwe ...[more]
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Project description:ObjectiveAs a potentially life-threatening condition, myasthenia gravis (MG) has limited epidemiological studies on mortality. We aim to provide demographic distribution, geographical variation, and temporal trend of MG-related mortality in China.MethodsThe national population-based analysis was conducted based on records derived from the National Mortality Surveillance System of China. All deaths related to MG were identified from 2013 to 2020, and MG-related mortality was evaluated by sex, age, location, and year.ResultsA total of 4224 deaths were related to MG during 2013-2020, and the median age at death of MG was 59.45 years, significantly lower than that in the general population (75.47 years, P < 0.05). In 2020, the age-standardized mortality rate of MG was 1.86 per million people and markedly higher in males than in females (2.37 vs. 1.31 per million). The mortality rate per million was lower than 1 in young children, peaking at 2.83 only in males (vs. 0.36 in females) aged 10-19 years, and substantially increased with age, reaching the highest rate of 13.31 for males and 10.58 for females aged 80 years and older. Geographical disparity across China was observed with the highest age-standardized mortality rate in Southwest (2.53 per million). From 2013 to 2020, MG-related mortality rate showed an increasing trend with the average annual percentage change of 3.5% (95% CI, 1.4-5.6). The notable increases occurred in age 10-19 years and over 70 years.InterpretationIn China, MG-related mortality was notably high among adolescent males and the elderly. The increasing death burden due to MG highlight challenges to disease management.
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Project description:BackgroundThe aim was to collate all myasthenia gravis (MG) epidemiological studies including AChR MG and MuSK MG specific studies. To synthesize data on incidence rate (IR), prevalence rate (PR) and mortality rate (MR) of the condition and investigate the influence of environmental and technical factors on any trends or variation observed.MethodsStudies were identified using multiple sources and meta-analysis performed to calculate pooled estimates for IR, PR and MR.Results55 studies performed between 1950 and 2007 were included, representing 1.7 billion population-years. For All MG estimated pooled IR (eIR): 5.3 per million person-years (C.I.:4.4, 6.1), range: 1.7 to 21.3; estimated pooled PR: 77.7 per million persons (C.I.:64.0, 94.3), range 15 to 179; MR range 0.1 to 0.9 per millions person-years. AChR MG eIR: 7.3 (C.I.:5.5, 7.8), range: 4.3 to 18.0; MuSK MG IR range: 0.1 to 0.32. However marked variation persisted between populations studied with similar methodology and in similar areas.ConclusionsWe report marked variation in observed frequencies of MG. We show evidence of increasing frequency of MG with year of study and improved study quality. This probably reflects improved case ascertainment. But other factors must also influence disease onset resulting in the observed variation in IR across geographically and genetically similar populations.
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Project description:ImportanceUse of biologic agents in generalized myasthenia gravis is generally limited to therapy-refractory cases; benefit in new-onset disease is unknown.ObjectiveTo assess rituximab in refractory and new-onset generalized myasthenia gravis and rituximab vs conventional immunotherapy in new-onset disease.Design, setting, and participantsA retrospective cohort study with prospectively collected data was conducted on a county-based community sample at Karolinska University Hospital, Stockholm, Sweden. Participants included 72 patients with myasthenia gravis, excluding those displaying muscle-specific tyrosine kinase antibodies, initiating rituximab treatment from January 1, 2010, to December 31, 2018, and patients with new-onset disease initiating conventional immunotherapy from January 1, 2003, to December 31, 2012, with 12 months or more of observation time. The present study was conducted from March 1, 2019, to January 31, 2020.ExposuresTreatment with low-dose rituximab (most often 500 mg every 6 months) or conventional immunosuppressants.Main outcomes and measuresTime to remission (main outcome) as well as use of rescue therapies or additional immunotherapies and time in remission (secondary outcomes).ResultsOf the 72 patients included, 31 patients (43%) were women; mean (SD) age at treatment start was 60 (18) years. Twenty-four patients had received rituximab within 12 months of disease onset and 48 received rituximab at a later time, 34 of whom had therapy-refractory disease. A total of 26 patients (3 [12%] women; mean [SD] age, 68 [11] years at treatment start) received conventional immunosuppressant therapy. Median time to remission was shorter for new-onset vs refractory disease (7 vs 16 months: hazard ratio [HR], 2.53; 95% CI, 1.26-5.07; P = .009 after adjustment for age, sex, and disease severity) and for rituximab vs conventional immunosuppressant therapies (7 vs 11 months: HR, 2.97; 95% CI, 1.43-6.18; P = .004 after adjustment). In addition, fewer rescue therapy episodes during the first 24 months were required (mean [SD], 0.38 [1.10] vs 1.31 [1.59] times; mean difference, -1.26; 95% CI, -1.97 to -0.56; P < .001 after adjustment), and a larger proportion of patients had minimal or no need of additional immunotherapies (70% vs 35%; OR, 5.47; 95% CI, 1.40-21.43; P = .02 after adjustment). Rates of treatment discontinuation due to adverse events were lower with rituximab compared with conventional therapies (3% vs 46%; P < .001 after adjustment).Conclusions and relevanceClinical outcomes with rituximab appeared to be more favorable in new-onset generalized myasthenia gravis, and rituximab also appeared to perform better than conventional immunosuppressant therapy. These findings suggest a relatively greater benefit of rituximab earlier in the disease course. A placebo-controlled randomized trial to corroborate these findings is warranted.
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Project description:BackgroundMyasthenia gravis (MG) is the most common primary disorder of neuromuscular transmission, but the incidence of MG in China is unknown. We conducted the first nationwide study to determine the incidence and mortality rates of MG in all age groups at the national level in China.MethodsThis national population-based registry study is based on the database of the Hospital Quality Monitoring System of National Health Commission, which covers 1665 hospitals providing myasthenia gravis care in 31 provinces and municipalities across China. 94,638 hospital admissions for 59,243 myasthenia gravis patients were identified from January 1st, 2016 to December 31st, 2018. Myasthenia gravis was identified by ICD-10 codes (G70). Incidence of myasthenia gravis was stratified by age, sex, and province.FindingsOf 59,243 patients, 30,503 individuals with myasthenia gravis were newly diagnosed. Age and sex adjusted incidence of myasthenia gravis was 0.68 per 100,000 person-years, with highest in the age group of 70-74 years. The incidence in females was 0.76 per 100,000 and 0.60 per 100,000 in males. The admission mortality rate was 14.69‰. Respiratory failure was the leading cause of death in patients with myasthenic crisis. There were 14,840 patients with thymomas, encompassing 14,636 (26.5%) adults and 204 (7.1%) juveniles. 9453 (63.7%) patients with thymomas underwent thymomectomy. The median length of hospital stay was 8 days (interquartile range (IQR) 4 to 15 days) with median hospitalization cost $1037 (IQR $493 to $2925). The Basic Medical Insurance was the most common payment method, covering 67.4% of patients.InterpretationThe age and sex adjusted incidence of MG was 0.68 per 100,000 person-years in China. The admission mortality rate was 14.69‰. Most cases of new onset MG occurred in the seventh decade of life.FundingNational Science Foundation of China (91642205, and 81830038); Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing.
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Project description:Myasthenia gravis (MG) is an heterogeneous autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane, in the neuromuscular junction. The contribution of genetic factors to MG susceptibility has been evaluated through family and twin studies however, the precise genetic background of the disease remains elusive. We conducted a case-control association study in 101 unrelated MG patients of Hellenic origin and 101 healthy volunteers in order to assess the involvement of common genetic variants in susceptibility to MG. We focused on three candidate genes which have been clearly associated with several autoimmune diseases, aiming to investigate their potential implication in MG pathogenesis. These are interferon regulatory factor 5 (IRF-5), TNF?-induced protein 3 (TNFAIP3), also known as A20, and interleukin-10 (IL-10), key molecules in the regulation of immune function. A statistical trend of association (P = 0.068) between IL-10 promoter single nucleotide polymorphisms (SNPs) and the subgroups of early and late-onset MG patients was revealed. No statistically significant differences were observed in the rest of the variants examined. As far as we are aware, this is the first worldwide attempt to address the possible association between IRF-5 and TNFAIP3 common genetic variants and the genetic basis of MG.
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