Dinesh Khanna1, Veronica J Berrocal1, Edward H Giannini2, James R Seibold3, Peter A Merkel4, Maureen D Mayes5, Murray Baron6, Philip J Clements7, Virginia Steen8, Shervin Assassi5, Elena Schiopu1, Kristine Phillips1, Robert W Simms9, Yannick Allanore10, Christopher P Denton11, Oliver Distler12, Sindhu R Johnson12, Marco Matucci-Cerinic13, Janet E Pope14, Susanna M Proudman15, Jeffrey Siegel16, Weng Kee Wong7, Athol U Wells17, Daniel E Furst7. 1. University of Michigan, Ann Arbor. 2. Cincinnati Children's Hospital, Cincinnati, Ohio. 3. Scleroderma Research Consultants, Litchfield, Connecticut. 4. University of Pennsylvania, Philadelphia. 5. University of Texas Health Science Center at Houston. 6. Jewish General Hospital and McGill University, Montreal, Quebec, Canada. 7. University of California, Los Angeles. 8. Georgetown University, Washington, DC. 9. Boston University, Boston, Massachusetts. 10. Paris Descartes University and Cochin Hospital, AP-HP, Paris, France. 11. Royal Free and University College London Medical School, London, UK. 12. Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada. 13. Azienda Ospedaliero-Universitaria Careggi (AOUC) and University of Florence, Florence, Italy. 14. Schulich School of Medicine, Western University, London Campus, and St. Joseph's Health Care, London, Ontario, Canada. 15. Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, Australia. 16. Genentech/Roche, San Francisco, California. 17. Royal Brompton Hospital, London, UK.
Abstract
OBJECTIVE: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs). METHODS: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT. RESULTS: Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02). CONCLUSION: We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc.
OBJECTIVE: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs). METHODS: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT. RESULTS: Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02). CONCLUSION: We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc.
Authors: P A Merkel; N P Silliman; P J Clements; C P Denton; D E Furst; M D Mayes; J E Pope; R P Polisson; J B Streisand; J R Seibold Journal: Arthritis Rheum Date: 2012-10
Authors: Lorinda Chung; Christopher P Denton; Oliver Distler; Daniel E Furst; Dinesh Khanna; Peter A Merkel Journal: Clin Exp Rheumatol Date: 2012-05-30 Impact factor: 4.473
Authors: Dinesh Khanna; Oliver Distler; Jerome Avouac; Frank Behrens; Philip J Clements; Christopher Denton; Ivan Foeldvari; Edward Giannini; Doerte Huscher; Otylia Kowal-Bielecka; Daniel Lovell; Marco Matucci-Cerinic; Maureen Mayes; Peter A Merkel; Peter Nash; Christian F Opitz; David Pittrow; Lewis Rubin; James R Seibold; Virginia Steen; C Vibeke Strand; Peter S Tugwell; John Varga; Angela Zink; Daniel E Furst Journal: J Rheumatol Date: 2009-10 Impact factor: 4.666
Authors: Dinesh Khanna; Otylia Kowal-Bielecka; Puja P Khanna; Anna Lapinska; Steven M Asch; Neil Wenger; Kevin K Brown; Philip J Clements; Terry Getzug; Maureen D Mayes; Thomas A Medsger; Ronald Oudiz; Robert Simms; Virginia Steen; Paul Maranian; Daniel E Furst Journal: Clin Exp Rheumatol Date: 2011-05-16 Impact factor: 4.473
Authors: Sogol Amjadi; Paul Maranian; Daniel E Furst; Philip J Clements; Weng Kee Wong; Arnold E Postlethwaite; Puja P Khanna; Dinesh Khanna Journal: Arthritis Rheum Date: 2009-08
Authors: Tanja A Stamm; Malin Mattsson; Carina Mihai; Juliane Stöcker; Alexa Binder; Bettina Bauernfeind; Georg Stummvoll; Gunvor Gard; Roger Hesselstrand; Gunnel Sandqvist; Oana Draghicescu; Ana Maria Gherghe; Malina Voicu; Klaus P Machold; Oliver Distler; Josef S Smolen; Carina Boström Journal: Ann Rheum Dis Date: 2011-06 Impact factor: 19.103
Authors: John D Pauling; Joana Caetano; Corrado Campochiaro; Giacomo De Luca; Ana Maria Gheorghiu; Maria Grazia Lazzaroni; Dinesh Khanna Journal: J Scleroderma Relat Disord Date: 2019-11-25
Authors: Ariane L Herrick; Deborah J Griffiths-Jones; W David Ryder; Justin C Mason; Christopher P Denton Journal: J Scleroderma Relat Disord Date: 2020-09-17