Author
Murat Inanc
Other affiliations: University College London, University of Pisa
Bio: Murat Inanc is an academic researcher from Istanbul University. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 19, co-authored 20 publications receiving 8996 citations. Previous affiliations of Murat Inanc include University College London & University of Pisa.
Papers published on a yearly basis
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Johns Hopkins University1, University of Alabama at Birmingham2, University of Birmingham3, Oklahoma Medical Research Foundation4, Laval University5, University of Manchester6, University College London7, University of California, Los Angeles8, Lund University9, Northwestern University10, Hanyang University11, Dalhousie University12, University of Toronto13, McGill University14, North Shore-LIJ Health System15, Allegheny General Hospital16, University of California, San Diego17, University of Pennsylvania18, Monklands Hospital19, University of the Basque Country20, St Thomas' Hospital21, University of Copenhagen22, New York University23, University of North Carolina at Chapel Hill24, Karolinska Institutet25, SUNY Downstate Medical Center26, University of Manitoba27, Wake Forest University28, University of Louisville29, Emory University30, Istanbul University31, Medical University of South Carolina32, University of Texas Health Science Center at San Antonio33, Cedars-Sinai Medical Center34, University of Maryland, Baltimore35
TL;DR: The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE.
Abstract: Objective The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Results Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). Conclusion The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or antidouble-stranded DNA antibodies. (Less)
3,609 citations
Radboud University Nijmegen Medical Centre1, University of Michigan2, Radboud University Nijmegen3, University of Toronto4, McGill University5, University of Basel6, University of Florence7, Auckland City Hospital8, University of Pittsburgh9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, University of Colorado Denver26, National Health Service27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, Rutgers University31, Thomas Jefferson University32, Amgen33, University of Toledo34, Boston University35, Medical University of South Carolina36, University of Pennsylvania37, Northwestern University38
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
2,743 citations
Radboud University Nijmegen1, University of Michigan2, University of Toronto3, McGill University4, University of Basel5, University of Florence6, Auckland City Hospital7, University of Pittsburgh8, Complutense University of Madrid9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, Amgen26, University of Colorado Denver27, Medical College of Wisconsin28, University of Alabama at Birmingham29, National Health Service30, University of Manchester31, Rutgers University32, Thomas Jefferson University33, University of Toledo34, Boston University35, University of Pennsylvania36, Medical University of South Carolina37, Northwestern University38, University of Western Ontario39
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud9s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
1,899 citations
Karolinska Institutet1, University of Pisa2, University of Crete3, University College London4, University of Münster5, Dresden University of Technology6, University of Groningen7, University of Manchester8, McGill University9, University of Pécs10, University Medical Center Utrecht11, Charité12, University of Birmingham13, Medical University of Graz14, Université catholique de Louvain15, Istanbul University16, Copenhagen University Hospital17, Rio de Janeiro State University18, University of Paris-Sud19, University of Santo Tomas Hospital20, Medical University of Vienna21, VU University Amsterdam22, Odense University Hospital23, Moscow State University24, Hairmyres Hospital25, University of Düsseldorf26
TL;DR: Treating-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative and it is anticipated that ‘treating- to-target’ can and will be applicable to the care of patients with SLE.
Abstract: The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.
521 citations
Central Manchester University Hospitals NHS Foundation Trust1, University College London2, Queen Elizabeth II Health Sciences Centre3, University of Pennsylvania4, Toronto Western Hospital5, Hanyang University6, University of Birmingham7, University of California, Los Angeles8, University of Calgary9, McGill University Health Centre10, SUNY Downstate Medical Center11, Oklahoma Medical Research Foundation12, University of Alabama at Birmingham13, Laval University14, Johns Hopkins University School of Medicine15, University of North Carolina at Chapel Hill16, King's College London17, Northwestern University18, Hairmyres Hospital19, The Feinstein Institute for Medical Research20, Karolinska Institutet21, University of California, San Diego22, University of the Basque Country23, Emory University24, Medical University of South Carolina25, University of Manitoba26, Istanbul University27
TL;DR: It is found that several potentially modifiable risk factors for damage accrual are identified and an integrated strategy to address these may improve long-term outcomes.
Abstract: We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients.
379 citations
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TL;DR: In this paper, the authors evaluated plasma heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc) and characterized its association with SSc-related features.
Abstract: Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.
2,948 citations
Radboud University Nijmegen Medical Centre1, University of Michigan2, Radboud University Nijmegen3, University of Toronto4, McGill University5, University of Basel6, University of Florence7, Auckland City Hospital8, University of Pittsburgh9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, University of Colorado Denver26, National Health Service27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, Rutgers University31, Thomas Jefferson University32, Amgen33, University of Toledo34, Boston University35, Medical University of South Carolina36, University of Pennsylvania37, Northwestern University38
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
2,743 citations
Radboud University Nijmegen1, University of Michigan2, University of Toronto3, McGill University4, University of Basel5, University of Florence6, Auckland City Hospital7, University of Pittsburgh8, Complutense University of Madrid9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, Amgen26, University of Colorado Denver27, Medical College of Wisconsin28, University of Alabama at Birmingham29, National Health Service30, University of Manchester31, Rutgers University32, Thomas Jefferson University33, University of Toledo34, Boston University35, University of Pennsylvania36, Medical University of South Carolina37, Northwestern University38, University of Western Ontario39
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud9s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
1,899 citations
University of Perugia1, Dresden University of Technology2, Leiden University Medical Center3, National and Kapodistrian University of Athens4, University of Padua5, University of Birmingham6, University of Ferrara7, Cliniques Universitaires Saint-Luc8, University of Cambridge9, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico10, University of Pisa11, University of Düsseldorf12, Medical University of Vienna13, Karolinska University Hospital14, Charles University in Prague15, University of Brescia16, Aarhus University Hospital17, University of Amsterdam18, University Hospital Bonn19
TL;DR: The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion, based on emerging new evidence.
Abstract: Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
1,079 citations
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, Medical University of South Carolina9, University of Cambridge10, University of Barcelona11, The Feinstein Institute for Medical Research12, Toronto Western Hospital13, University of California, Los Angeles14, Humboldt University of Berlin15, Copenhagen University Hospital16, University of Michigan17, University of the Basque Country18, University Health Network19, University of Crete20, University of Zagreb21, University of Paris-Sud22, University of Hong Kong23, University of Calgary24, Hospital for Special Surgery25, University of Pécs26, University of Padua27, Medical University of Graz28, National Institutes of Health29, New York University30, Université Paris-Saclay31, University Hospital Complex Of Vigo32, University of Occupational and Environmental Health Japan33, University of Porto34, Leeds Teaching Hospitals NHS Trust35, Cedars-Sinai Medical Center36, Istanbul Bilim University37, McMaster University38
TL;DR: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism and the American College of Rheumatology (ACR).
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
1,018 citations