ABSTRACT
OBJECTIVE: To study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Data from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. RESULTS: A total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. CONCLUSION: Our study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.
ABSTRACT
Idiopathic inflammatory myopathies (IIM) impact all aspects of health, physiological, physical, and psychological. Hallmark symptoms of IIM are muscle weakness, reduced muscle endurance and aerobic capacity. Recently, pain and fatigue as well as anxiety and depression have emerged as common and debilitating symptoms in patients with IIM. The aim of this scoping review is to, in a holistic way, describe how IIM impact patients' physiological, physical, and psychological health and how exercise has a role to treat as well as potentially counteract the effects of the disease. Inflammation induces non-immune response and organ damage. These changes with additional impact of physical inactivity lead to muscle impairment and reduced aerobic capacity. Pain, fatigue and low psychological well-being and overall quality of life are also common health aspects of IIM. Medical treatment can reduce inflammation but has in turn serious side effects such as muscle atrophy, type-II diabetes, and hypertension, which exercise has the potential to treat, and perhaps also counteract. In addition, exercise improves muscle function, aerobic capacity and might also reduce fatigue and pain. New evidence shows that reducing systemic inflammation may also improve patient-reported subjective health, quality of life and psychological well-being. Exercise in combination with medical treatment is becoming an important part of the treatment for patients with IIM as exercise has the potential to promote health aspects of various dimensions in patients with IIM.
ABSTRACT
AIM: To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM). METHODS: PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function. RESULTS: PGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity. CONCLUSION: Increased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials.
Subject(s)
Myositis , Male , Humans , Female , Longitudinal Studies , Myositis/complications , Inflammation , Outcome Assessment, Health Care , Blood SedimentationABSTRACT
OBJECTIVE: To identify predictors of response to immunosuppressive therapy after 1 year, with a focus on autoantibodies, in patients newly diagnosed with idiopathic inflammatory myopathies (IIM) followed longitudinally in an electronic registry. METHODS: We assessed the association between autoantibody-defined groups and improvement according to American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 response criteria. RESULTS: We identified 156 patients; of those, 111 (71%) were positive for any autoantibody tested, 90% received glucocorticoid treatment at baseline, and 78% received immunosuppressive drugs at some follow-up point. After 1 year from the index date, the overall median improvement score was 27.5 (interquartile range 10-51). No differences were observed in the total improvement score between the autoantibody-defined groups. Overall, 62% of patients (n = 96) showed a minimal response, 38% (n = 60) achieved a moderate response, and 19% (n = 30) achieved a major response. Regarding the different levels of response, dermatomyositis-specific autoantibodies were associated with a moderate response versus the seronegative group (reference), odds ratio 4.12 (95% confidence interval 1.2-16.5). In addition, dysphagia, time from symptom onset to diagnosis, and initial glucocorticoid dose were significant predictors of response after 1 year of follow-up. CONCLUSION: Patients with DM-specific autoantibodies achieved better levels of response compared to other autoantibody-defined groups. Dysphagia, a shorter time span from symptom onset to diagnosis, and intensive initial immunosuppressive treatment were associated with a higher response rate after 1 year of pharmacologic treatment from the index date, regardless of autoantibody status.
Subject(s)
Immunosuppressive Agents/therapeutic use , Myositis/drug therapy , Aged , Autoantibodies/immunology , Female , Glucocorticoids/therapeutic use , Humans , Male , Middle Aged , Myositis/immunology , Registries , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: The current biomarkers for diagnosis and monitoring of injured and diseased skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic accuracy are needed. Our aim was to develop and validate a novel assay for skeletal troponin I (skTnI), and to assess its clinical performance in patients with idiopathic inflammatory myopathies (IIM). METHODS: A two-step fluoroimmunoassay was used to analyze samples from healthy reference individuals (n = 140), patients with trauma (n = 151), and patients with IIM (n = 61). RESULTS: The limit of detection was 1.2 ng/mL, and the upper reference limit (90th percentile) was 5.2 ng/mL. The median skTnI concentrations were Subject(s)
Biomarkers
, Myositis/blood
, Myositis/diagnosis
, Troponin I/blood
, Adult
, Aged
, Biological Assay/methods
, Biological Assay/standards
, Female
, Fluoroimmunoassay/methods
, Fluoroimmunoassay/standards
, Humans
, Male
, Middle Aged
, Muscle, Skeletal/metabolism
, Muscle, Skeletal/pathology
, Myositis/etiology
, Reproducibility of Results
, Sensitivity and Specificity
, Young Adult
Subject(s)
Myositis , Polymyositis , Algorithms , Autoantibodies , Humans , Immunoprecipitation , Myositis/drug therapyABSTRACT
Cost-minimization study to assess the annual direct costs of 2 antiresorptive strategies in postmenopausal women with low bone mineral densities (BMDs). Patients were randomly assigned to receive 70 mg of oral weekly alendronate or a 1-time 5mg of intravenous zoledronic acid. All medical and nonmedical direct costs were recorded for 1 yr. Student's t-test or the Chi-squared test was used. A total of 101 postmenopausal women were enrolled with a mean age of 58.3 ± 7.6 yr and a postmenopausal period of 13.5 ± 8.3 yr. A total of 50 patients completed 1 yr of alendronate and 51 patients received zoledronic acid. At baseline, no differences were seen between the 2 groups in anthropometric measures, comorbidities, and bone mineral density. The costs for medical attention for low bone mass were $81,532 (US Dollars) for the alendronate group and $69,251 for the zoledronic acid group; the cost per patient was $1631 in the alendronate group vs $1358 in the zoledronic acid group (p<0.0001). Therefore, zoledronic acid treatment provided an annual savings of 15% of the direct costs compared with oral alendronate treatment. Moreover, there was a significant increase in lumbar spine T-scores in the zoledronic acid group when compared with the alendronate group. Annual zoledronic acid infusion as an antiresorptive treatment in women with low BMD provides significant monetary savings when compared with weekly alendronate therapy for 1 yr. Zoledronic acid infusion is also linked to higher increase in BMD and compliance.