OBJECTIVE: The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening. METHODS: Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC. RESULTS: Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories. CONCLUSION: The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials.

• Klíčová slova
• DM, PM, clinical trial, myositis, outcome assessment, outcome measure, response criteria,
• MeSH
• dermatomyozitida * farmakoterapie   MeSH
• dospělí MeSH
• konsensus MeSH
• lidé MeSH
• myozitida * farmakoterapie   MeSH
• polymyozitida * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH

OBJECTIVES: The 2016 ACR-EULAR Response Criteria for JDM was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, and frequency of CSM worsening across myositis response criteria (MRC) categories in validation of MRC. METHODS: Data from JDM patients in the Rituximab in Myositis trial (n = 48), PRINTO JDM trial (n = 139), and consensus patient profiles (n = 273) were included. Observed vs expected CSM contributions were compared using Sign test. Characteristics of MRC categories were compared by Wilcoxon tests with Bonferroni adjustment. Spearman correlation of changes in TIS and individual CSMs were examined. Agreement between physician-assessed change and MRC categories was evaluated by weighted Cohen's kappa. RESULTS: Of 457 JDM patients with IMACS CSMs and 380 with PRINTO CSMs, 9-13% had minimal, 19-23% had moderate and 41-50% had major improvement. The number of improved and absolute percentage change of CSMs increased by MRC improvement level. Patients with minimal improvement by MRC had a median of 0-1 CSM worsened, and those with moderate/major improvement had a median of zero worsening CSMs. Of patients improved by MRC, 94-95% had improvement in muscle strength and 93-95% had improvement in ≥1 patient-reported CSM. IMACS and PRINTO CSMs performed similarly. Physician-rated change and MRC improvement categories had moderate-to-substantial agreement (Kappa 0.5-0.7). CONCLUSION: The ACR-EULAR MRC perform consistently across multiple studies, supporting its further use as an efficacy end point in JDM trials.

• Klíčová slova
• JDM, clinical trial, myositis, outcome assessment, outcome measure, response criteria,
• MeSH
• dermatomyozitida * farmakoterapie   MeSH
• konsensus MeSH
• lidé MeSH
• myozitida * farmakoterapie   MeSH
• rituximab terapeutické užití   MeSH
• svalová síla MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• rituximab MeSH

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that these are systemic inflammatory disorders. Different myositis-specific autoantibodies have been identified and, on the basis of clinical, histopathological and serological features, IIMs can be classified into several subgroups — dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the autoantigens of the immune reactions in these subgroups is crucial to improve outcomes. New, more homogeneous subgroups defined by autoantibodies may help define disease mechanisms, and will also be important in future clinical trials to develop targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.

• MeSH
• lidé MeSH
• myozitida * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM." CONCLUSION: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

• MeSH
• biopsie normy   MeSH
• dítě MeSH
• dospělí MeSH
• konsensus MeSH
• kosterní svaly patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myozitida klasifikace   diagnóza   MeSH
• revmatologie normy   MeSH
• senzitivita a specificita MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• společnosti lékařské MeSH
• určení symptomu metody   normy   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. CONCLUSIONS: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

• Klíčová slova
• autoimmune diseases, dermatomyositis, polymyositis,
• MeSH
• biopsie normy   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• dospělí MeSH
• konsensus MeSH
• kosterní svaly patologie   MeSH
• lidé MeSH
• myozitida klasifikace   diagnóza   MeSH
• pravděpodobnost MeSH
• referenční hodnoty MeSH
• revmatologie organizace a řízení   normy   MeSH
• senzitivita a specificita MeSH
• společnosti lékařské organizace a řízení   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• směrnice pro lékařskou praxi MeSH
• validační studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

OBJECTIVE: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. METHODS: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. RESULTS: Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. CONCLUSION: Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.

• Klíčová slova
• 1000Minds software, conjoint analysis, dermatomyositis, hybrid measure, juvenile dermatomyositis, outcome assessment, polymyositis, response criteria,
• MeSH
• dermatomyozitida terapie   MeSH
• lidé MeSH
• logistické modely MeSH
• minimální klinicky významný rozdíl MeSH
• plocha pod křivkou MeSH
• polymyozitida terapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH

OBJECTIVE: To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). METHODS: 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. RESULTS: Consensus was reached for a conjoint analysis-based continuous model using absolute percent 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). CONCLUSION: The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute percent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.

• MeSH
• alanintransaminasa metabolismus   MeSH
• aldolasa metabolismus   MeSH
• antirevmatika terapeutické užití   MeSH
• aspartátaminotransferasy metabolismus   MeSH
• dermatomyozitida farmakoterapie   metabolismus   patofyziologie   MeSH
• hodnocení výsledků péče pacientem MeSH
• hodnocení výsledků zdravotní péče MeSH
• kreatinkinasa metabolismus   MeSH
• L-laktátdehydrogenasa metabolismus   MeSH
• lidé MeSH
• logistické modely MeSH
• polymyozitida farmakoterapie   metabolismus   patofyziologie   MeSH
• průzkumy a dotazníky MeSH
• revmatologie MeSH
• společnosti lékařské MeSH
• svalová síla MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH
• Názvy látek
• alanintransaminasa MeSH
• aldolasa MeSH
• antirevmatika MeSH
• aspartátaminotransferasy MeSH
• kreatinkinasa MeSH
• L-laktátdehydrogenasa MeSH

OBJECTIVE: To develop response criteria for juvenile dermatomyositis (DM). METHODS: We analyzed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. RESULTS: Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute percent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (P = 0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (P < 0.006). CONCLUSION: The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute percent change in core set measures, with thresholds for minimal, moderate, and major improvement.

• MeSH
• alanintransaminasa metabolismus   MeSH
• aldolasa metabolismus   MeSH
• antirevmatika terapeutické užití   MeSH
• aspartátaminotransferasy metabolismus   MeSH
• cyklosporin terapeutické užití   MeSH
• dermatomyozitida farmakoterapie   metabolismus   patofyziologie   MeSH
• dítě MeSH
• glukokortikoidy terapeutické užití   MeSH
• hodnocení výsledků péče pacientem MeSH
• hodnocení výsledků zdravotní péče MeSH
• kreatinkinasa metabolismus   MeSH
• L-laktátdehydrogenasa metabolismus   MeSH
• lidé MeSH
• logistické modely MeSH
• methotrexát terapeutické užití   MeSH
• mladiství MeSH
• prednison terapeutické užití   MeSH
• průzkumy a dotazníky MeSH
• reprodukovatelnost výsledků MeSH
• revmatologie MeSH
• rituximab terapeutické užití   MeSH
• společnosti lékařské MeSH
• svalová síla MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH
• Názvy látek
• alanintransaminasa MeSH
• aldolasa MeSH
• antirevmatika MeSH
• aspartátaminotransferasy MeSH
• cyklosporin MeSH
• glukokortikoidy MeSH
• kreatinkinasa MeSH
• L-laktátdehydrogenasa MeSH
• methotrexát MeSH
• prednison MeSH
• rituximab MeSH

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.

• Klíčová slova
• Dermatomyositis, Polymyositis, Treatment,
• MeSH
• dermatomyozitida terapie   MeSH
• dítě MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče normy   MeSH
• konsensus MeSH
• lidé MeSH
• mladiství MeSH
• polymyozitida terapie   MeSH
• předškolní dítě MeSH
• randomizované kontrolované studie jako téma MeSH
• senzitivita a specificita MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• směrnice pro lékařskou praxi MeSH
• validační studie MeSH

To develop response criteria for juvenile dermatomyositis (DM). We analysed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute per cent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (p=0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (p<0.006). The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute per cent change in core set measures, with thresholds for minimal, moderate, and major improvement.

• Klíčová slova
• Dermatomyositis, Polymyositis, Treatment,
• MeSH
• dermatomyozitida terapie   MeSH
• dítě MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče normy   MeSH
• konsensus MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• randomizované kontrolované studie jako téma MeSH
• senzitivita a specificita MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• směrnice pro lékařskou praxi MeSH
• validační studie MeSH