| 1. |
- Aggarwal, R, et al.
(författare)
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2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative
- 2017
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:5, s. 792-801
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Tidskriftsartikel (refereegranskat)abstract
- To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0–100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.
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| 2. |
- Alexanderson, H., et al.
(författare)
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FATIGUE IN ADULT IDIOPATHIC INFLAMMATORY MYOPATHIES
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ PUBLISHING GROUP. - 0003-4967 .- 1468-2060. ; 74, s. 106-106
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
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| 4. |
- Demirdal, D, et al.
(författare)
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CHARACTERISATION OF SWEDISH MYOSITIS PATIENTS WITH ANTI-MDA5 AUTOANTIBODIES AND CORRELATION OF CLINICAL FEATURES WITH AUTOANTIBODY LEVELS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 751-752
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The association between anti-melanoma differentiation association protein 5 autoantibodies (aMDA5) and rapidly progressive interstitial lung disease (RP-ILD) in clinically amyopathic dermatomyositis is well established in Asian population cohorts. In western cohorts, ILD has been strongly associated with aMDA5 but data regarding RP-ILD have been more conflicting. It is also suggested that western cohorts have more pronounced myopathic features than Asian.ObjectivesTo characterise the disease manifestations of a Swedish aMDA5 positive idiopathic inflammatory myositis (IIM) cohort and to explore antigen reactivity of the MDA5 protein.MethodsFirst available serum samples collected from 28 consecutive patients with IIM and positive aMDA5 ever tested by ELISA, Line Blot (LB) or Immunoprecipitation, attending Karolinska University Hospital between 1999 and 2021, were included. Clinical data including presence of anti-SSA autoantibodies by ELISA or LB was retrieved retrospectively. An in-house ELISA was used to screen serum samples for reactivity against a recombinant MDA5 protein (rMDA5, aa A110-D1025, UniProt ID Q9BYX4) and seven MDA5-derived constructs containing different domains. Correlations between aMDA5 reactivity levels and clinical data were explored.ResultsNine patients showed no reactivity to any of the rMDA5 constructs by ELISA and were excluded from further analysis.Reactivity against rMDA5 was confirmed by ELISA in 19 patients (median 184.7 µg/mL (interquartile range (IQR) 277.07). The cohort included 13 male and 6 female patients, 94% Caucasian, with mean age at diagnosis of 41.05 years (standard deviation (SD) 10.5). Median disease duration at time of sampling was 0 months (IQR 1). All patients except one had signs of muscle involvement (muscle weakness, elevated muscle enzymes, muscle oedema or muscle biopsy consistent with myositis). At diagnosis 63.2% of patients reported muscle weakness (21.1 % had a manual muscle test 8 score <75). Dermatological findings were observed in 17/19 (89.7 %). During disease course nine patients (47.4%) had confirmed arthritis.ILD was diagnosed in 16/19 patients (84.2%), four of these (25%) developed a RP-ILD. One patient passed away due to RP-ILD and one required a lung transplant. Patients with ILD had a statistically significant higher mean age at diagnosis than those without (42.8.5 (SD 10.3) vs 31.3 (SD 4.7) years, p=0.02). Patients developing RP-ILD were not significantly older than patients with chronic ILD. Respiratory symptoms were reported by 75% of patients with ILD at time of diagnosis. The mean total lung capacity (TLC) of the ILD cohort was 68% (SD 17), mean diffusion capacity of carbon monoxide (DLCO) was 59% (SD 15) and mean forced vital capacity (FVC) was 62% (SD 19). There was a higher proportion of patients with CRP ≥ 3 times the reference range at diagnosis amongst patients with FVC <70 % than patients with FVC >70 % (88.9 % vs 16.7 %, p= 0.01).Ten patients (52.6%) had anti-SSA autoantibodies, all had ILD. Anti-SSA positive patients had a statistically significant lower TLC than those without (62% vs 79% respectively, p=0.04) and a lower FVC (57% vs 76% respectively, p=0.05).We found a weak non-statistically significant negative correlation between titres of aMDA5 and TLC, DLCO and FVC (Pearson coefficients -0.187, -0.289, -0.130 respectively). Frequency of ILD was higher in patients with aMDA5 titres >100 µg/mL than those with titers <100, but not statistically significant (81.3% vs 18.8%, respectively).ConclusionIn this Caucasian cohort of aMDA5 positive IIM patients, ILD was present in over 80% of patients, of these, one quarter had RP-ILD. Older patients were more likely to present with ILD. Anti-SSA positivity and higher CRP levels were associated with worse lung function. We found a weak negative correlation between aMDA5 titres and lung function tests, as well as a trend of higher frequency of ILD in patients with higher aMDA5 titres. Muscle and skin involvement were found in a high proportion of patients.AcknowledgementsD. Demirdal & E. Van Gompel contributed equally to this abstract.Disclosure of InterestsDeniz Demirdal: None declared, Eveline Van Gompel: None declared, Edvard Wigren: None declared, Maryam Dastmalchi: None declared, Begum Horuluoglu: None declared, Angeles Shunashy Galindo-Feria: None declared, Susanne Gräslund: None declared, Karine Chemin: None declared, Ingrid E. Lundberg Shareholder of: Roche and Novartis., Consultant of: Consulting fees from Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Research grants from Astra Zeneca, Antonella Notarnicola Speakers bureau: compensation for lecture at conference sponsored by Boehringer Ingelheim.
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| 5. |
- Espinosa-Ortega, F, et al.
(författare)
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AUTOANTIBODIES CAN PARTLY PREDICT SEVERITY OF DAMAGE BUT NOT EXTENT IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOSITIS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 398-399
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients with idiopathic inflammatory myopathies (IIM) might suffer from irreversible damage once inflammation has decreased. Autoantibodies are found in up to 80% of patients with IIM and are coupled with specific clinical features. Whether autoantibodies can be used as biomarkers to predict patterns of damage in IIM remains unknown.Objectives:To investigate the association between autoantibodies and organ damage in patients with IIM using longitudinal national register data.Methods:Data were retrieved from the electronic Swedish Rheumatology Quality Register (SRQ). Patients (n=302) with a clinical diagnosis of IIM (2017 EULAR/ACR criteria) were included. Autoantibody status was tested by either line blot or RNA- and protein immunoprecipitation; HMGCR and FHL-1 autoantibodies were tested by ELISA. Patients were grouped into six categories of autoantibodies (Table 1). TheMyositis Damage Index(MDI) score was applied to measure organ damage using both components (extentandseverity) as a continuous variable and were analyzed using generalized estimating equations (GEE). A categorical variable for each time point of MDI assessment since diagnosis was created to adjust for time (Table 2). A base model which included autoantibody group and time was fit. Other potential predictors included age at diagnosis, sex, disease duration from diagnosis to inclusion to SRQ, arthritis, Raynaud, mechanics’ hands and heart involvement at registry; core set measures at each MDI time point allowing multiple longitudinal observations were also tested.Table 1.Clinical diagnosis and autoantibody groups.DiagnosisN (%)Polymyositis119 (38)Dermatomyositis (DM)99 (33)Inclusion body myositis35 (12)Amyopathic DM9 (3)Juvenile DM8 (3)Low probability myositis32 (11)Autoantibody286 (%)Antisynthetase (AS)74 (26)Necrotizing myopathy NM)20 (7)DM- specific44 (15)FHL-118 (6)Associated antibodies AA)50 (18)Negative to any80 (28)AS: Jo1, PL7, PL12, EJ, OJ;NM: SRP, HMGCR;DM-specific: TIF1γ, Mi2, MDA5, SAE;AA: Ro52, PmScl, U1RNP, KU.Table 2.Predictors of damage severity and extent.EstimateP valueSeverityTime#0.20NSAutoantibody group1Negativereference--Antisynthetase-0.6NSIMNM1.6NSDM- specific-2.6**FHL-10.4NSAssociated0.7NSMMT score1-0.1***ExtentTime#0.33NSCK, mkat/L2-0.006*#Time from diagnosis to MDI. *<0.05**<0.01***<0.0011. Adjusted for gender + disease duration + time.2. Adjusted for disease duration + time.Results:Mean age at diagnosis was 54 years (SD 16), 205 were female (68%), median disease duration was 4 months (IQR 1-39). Clinical diagnosis and the autoantibody groups are shown in Table 1. The median time from diagnosis to the first MDI assessment was 2.2 years (IQR 1.2 – 5.5), 227 patients had a second MDI assessment at median 4.5 years (3.3-8.6 years) and 114 patients had a third assessment at 7.8 (5.8-9.9) years.Severity of damage:Only the DM-specific autoantibodies (P = 0.01) and manual muscle test score (MMT) (P = 0.007) were independent negative predictors; disease duration was a positive predictor (P = 0.01).Extent of damage: Autoantibodies were not significant predictors; creatine kinase (CK) levels were negative predictors (P = 0.01) (Table 2).Conclusion:Presence of DM-specific autoantibodies, a high MMT score over time and short disease duration seem to predict less damage severity whereas high CK levels seem to predict of less extent of damage. These findings indicate that some myositis specific autoantibodies may serve as predictors of damage along with other clinical measures.References:[1]Sultan SM, et al. Interrater reliability and aspects of validity of the myositis damage index. Annals of the Rheumatic Diseases. 2011;70:1272-6.Disclosure of Interests:Fabricio Espinosa-Ortega: None declared, Marie Holmqvist: None declared, Maryam Dastmalchi: None declared, Andrew Mammen: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helene Alexanderson: None declared
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| 6. |
- Helmers, S.B., et al.
(författare)
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Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies
- 2007
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1276-1283
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (IVIG) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) patients. Methods: Thirteen treatment-resistant patients, 6 PM, 4 DM, 2 IBM and 1 juvenile DM, were treated with 2 g/kg of IVIG, three times at monthly intervals. Functional Index in Myositis and serum creatinine kinase (CK) levels were determined, and muscle biopsies were performed before treatment and after the third IVIG infusion. Immunological molecules were also studied in biopsies taken 24-48 h after the first infusion. Results: Improved muscle function was observed in three patients (1 PM, 1 DM and 1 IBM) and CK levels decreased in five. T cells, macrophages, major histocompatibility complex (MHC) class I antigen on muscle fibres, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and membranolytic attack complex (MAC) deposits on capillaries were present to an equal degree in biopsies before and after MG treatment. No correlation between the clinical response and molecular changes was found. Conclusions: The clinical effects of high-dose IVIG on muscle function in patients with refractory inflammatory active myositis did not correspond to effects on any of the investigated molecules in our study. T cells, macrophages, phenotypical changes in muscle fibres and endothelial cell activation were still present after treatment. These observations question a role for IVIG as an immune-modulating therapy in patients with inflammatory myopathies.
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