Subsets in Systemic Sclerosis-ILD: Working Towards Consensus-Based Definitions

David Roofeh¹, Kevin Brown ², Donald Tashkin ³, Shervin Assassi ⁴, Shaney Barratt ⁵, Elana Bernstein ⁶, Nitin Bhatt ⁷, Lorinda Chung ⁸, Harold Collard ⁹, Richard Conway ¹⁰, Paul Dellaripa ¹¹, Christopher Denton ¹², Oliver Distler ¹³, Robyn Domsic ¹⁴, Tracy J. Doyle ¹⁵, Puneet Garcha ¹⁶, Nishant Gupta ¹⁷, Anna Maria Hoffmann-Vold ¹⁸, Vivien Hsu ¹⁹, Francesca Ingegnoli ²⁰, Kerri Johannson ²¹, Bashar Kahaleh ²², Leticia Kawano-Dourado ²³, Ella Kazerooni ¹, Surabhi Khanna ¹⁷, Peter Korsten ²⁴, Celia JF Lin ²⁵, Toby Maher ²⁶, Stephen Mathai ²⁷, Fernando Martinez ²⁸, Eric Matteson ²⁹, Vivek Nagaraja ³⁰, Chester Oddis ³¹, Juan Ovalles-Bonilla ³², John Pauling ³³, Ganesh Raghu ³⁴, Ignasi Rodriguez-Pinto ³⁵, Ivan Rosas ¹⁵, James Seibold ³⁶, Virginia Steen ³⁷, Vibeke Strand ³⁸, Elizabeth Volkmann ³⁹, Dharshan Vummidi ³⁰, Simon Walsh ⁴⁰, Donald Zoz ⁴¹, Athol Wells ⁴² and Dinesh Khanna ⁴³, ¹University of Michigan, Ann Arbor, ²National Jewish Health, Denver, ³University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, ⁴Division of Rheumatology and Clinical Immunogenetics, University of Texas McGovern Medical School, Houston, Texas, USA, Houston, TX, ⁵North Bristol NHS Trust, Bristol, England, United Kingdom, ⁶Columbia University, New York City, ⁷Ohio State University Wexner Medical Center, Columbus, ⁸Stanford University, Palo Alto, CA, ⁹University of California San Fransisco, San Fransisco, ¹⁰Blackrock Clinic, Dublin, Ireland, ¹¹Brigham and Women's Hospital, Boston, MA, ¹²University College London Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, UK, London, United Kingdom, ¹³Dept. of Rheumatology, University Hospital Zürich, Zürich, Switzerland, Zürich, Switzerland, ¹⁴University of Pittsburgh, Pittsburgh, PA, ¹⁵Brigham and Women's Hospital, Harvard Medical School, Boston, ¹⁶Baylor Scott & White Health, Dallas, ¹⁷University of Cincinnati, Cincinnati, ¹⁸Department of Rheumatology, Oslo University Hospital, Oslo, Norway, Oslo, Norway, ¹⁹Rutgers- RWJ Medical School, SOUTH PLAINFIELD, NJ, ²⁰Division of Clinical Rheumatology, ASST Pini-CTO, Università degli Studi di Milano, Department of Clinical Sciences and Community Health, Milan, Italy, Milano, Italy, ²¹University of Calgary, Calgary, ²²University of Toledo, Toledo, OH, ²³University of Sao Paulo, Sao Paulo, Brazil, ²⁴University Medical Center Göttingen, Göttingen, Germany, ²⁵Genentech, San Fransisco, ²⁶National Heart and Lung Institute, Imperial College London, UK and National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, UK, London, United Kingdom, ²⁷John Hopkins Pulmonary and Critical Care Medicine, Baltimore, ²⁸Will Cornell Medicine Pulmonary & Critical Care Medicine, New York, ²⁹Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA, Rochester, ³⁰University of Michigan, Ann Arbor, MI, ³¹University of Pittsburgh Medical Center, Pittsburgh, PA, ³²Hospital Gregorio Marañón, Madrid, Spain, ³³Department of Rheumatology, Royal National Hospital of Rheumatic Diseases, Royal United Hospitals NHS Foundation Trusts, Bath, England, United Kingdom, ³⁴University of Washington, Seattle, USA, Seattle, ³⁵University of Barcelona, Barcelona, Spain, ³⁶Scleroderma Research Consultants LLC, Aiken, South Carolina, USA, Aiken, ³⁷Georgetown University, Washington, D.C., USA, Georgetown, ³⁸Division of Immunology/Rheumatology, Stanford University, Stanford, CA, ³⁹University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, ⁴⁰Kings College London, London, United Kingdom, ⁴¹Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA, Ridgefield, CT, ⁴²Royal Bromptom Hospital, London, United Kingdom, ⁴³Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA, Ann Arbor

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: systemic sclerosis and interstitial lung disease

Session Information

Date: Tuesday, November 12, 2019

Session Title: Systemic Sclerosis & Related Disorders – Clinical Poster III

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic sclerosis associated interstitial lung disease (SSc-ILD) is heterogeneous, with varying degrees of severity and risk of disease progression. No consensus-based definitions of disease severity, progression, or risk of progression exist. The purpose of this study was to use expert classification of real-world cases of SSc-ILD to derive definitions of SSc-ILD subsets that can be incorporated into clinical practice and trials.

Methods: All patients included in this study met American College of Rheumatology Criteria for Systemic Sclerosis (N=80).

Patient profiles were developed from participants in the Scleroderma Lung Study-II and ILD patients seen at a Scleroderma Center. Experts in rheumatology, pulmonary medicine, radiology, and members of the OMERACT CTD-ILD Working Group ¹ provided key domains to be included in profiles. These included information on demographics, disease features (limited vs. diffuse SSc, ANA status, antibody status), pulmonary function testing, patient-reported assessments, and quantitative analysis of lung involvement on high resolution computerized tomography of the chest (HRCT) for baseline profiles; and for those with follow-up data, how these measures change over time.

Eighty-three ILD experts were surveyed for classification of 80 baseline and 40 follow-up profiles. Baseline profiles were classified based on: 1- Severity (clinical vs. subclinical) and 2- Risk of Progression (low vs. high); follow-up profiles were classified on 3- Progression over time (stable vs. progressive vs. improved). Each profile was rated by a minimum of 4 experts; consensus on a classification was achieved with 75% concordance. For each profile, experts provided input on the top features that helped in making their classification decision.

Results: Fifty percent (N=42) of invited experts, from 10 countries, completed the survey.

Along the dimensions of severity, risk of progression, and progression, a majority of profiles achieved consensus ratings (Figure). Of those profiles achieving consensus, the majority were classified as “clinical ILD”, “low risk”, and “stable”. Table provides a ranking of the most influential features used in classification on these dimensions.

Conclusion: These data represent the first step in creating operational definitions for ILD subsets. This expert-derived classification advances the characterization of a subset of severity (clinical ILD), subsets of risk of progression (low and high risk), and a subset of progression (stable ILD).

Features used to classify profiles on severity and progression overlapped (forced vital capacity, whole lung involvement on HRCT, dyspnea ratings), whereas the risk of progression was influenced by disease duration, type of SSc, and SSc autoantibodies in addition to the measures endorsed for severity and progression.

The next steps are to reach operational definitions for those ILD subsets not yet reaching consensus (subclinical ILD, progressive ILD, improved ILD).

REFERENCES

Khanna, D. et al. J. Rheumatol. 42, 2168–2171 (2015)

Acknowledgment: Dr. D. Khanna is funded by NIH/NIAMS K24 AR063120 and RO1 AR070470

ACR Abstract_6 1_2019 FIGURE

Figure: Percent Profiles Achieving Consensus and Distribution of Consensus Profiles by ILD Subset

ACR Abstract_6 1_2019 TABLE

Table: The Most Influential Factors Used in Classification by Dimension

Disclosure: D. Roofeh, None; K. Brown, NIH, 2, Biogen, 5, Blade, 5, Boehringer Ingelheim, 5, Galapagos, 5, Galecto, 5, Genoa, 5, Lifemax, 5, MedImmune, 5, monARC, 5, Bionetworks, 5, OSIC, 5, Pilant, 5, ProMetic, 5, Third Pole, 5, Theravance, 5, Three Lakes Partners, 5, Veracyte, 5; D. Tashkin, None; S. Assassi, Bayer, 2, Boehringer Ingelheim, 2, 5, 8, Integrity Continuing Education, 8, 9, Medscape, 8, 9, Momenta, 2; S. Barratt, None; E. Bernstein, NIH/NIAMS, 2; N. Bhatt, None; L. Chung, BMS, 6, 9, Boehrenger-Ingelheim, 5, Boehringer Ingelheim, 5, Boehringer-Ingelheim, 5, Bristol-Myers Squib, 5, Eicos, 5, 6, 9, Eicos Steering Committee, 5, Mitsubishi Tanabe, 5, Reata, 5, 6, Reata DSMB, 5, Reatta, 5; H. Collard, None; R. Conway, None; P. Dellaripa, Bristol Myers Squibb, 2, Genentech, 2, UpToDate, 7; C. Denton, Actelion, 5, Actelion Pharmaceuticals, 5, Actelion, GlaxoSmithKline, Bayer, Sanofi, lnventiva, Boehringer Ingelheim, Roche, Bristol Myers Squibb, CSL Behring, UCB, Leadiant Biosciences, 5, Bayer, 5, Boehringer Ingelheim, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 5, Corbus Pharmaceuticals, 5, CSL Behring, 2, 5, GlaxoSmithKline, 2, 5, Inventiva, 2, 5, Leadiant Biosciences, 2, 5, lnventiva, 5, Pfizer, 5, Roche, 5, Sanofi, 5, UCB, 5; O. Distler, A. Menarini, 5, Abbvie, Acceleron, 5, Acceleron Pharma, 5, Actelion, 2, 5, 8, Actelion Pharmaceuticals, 2, 5, 8, 9, Amgen, 5, AnaMar, 2, 5, Bayer, 2, 5, 8, 9, Biogen Idec, 2, 5, Blade Therapeutics, 5, Boehringer Ingelheim, 2, 5, 8, 9, Catenion, 5, 9, ChemomAb, 2, 5, ChemomAB, 5, CSL Behring, 5, Ergonex, 5, espeRare Foundation, 2, 5, Genentech/Roche, 2, 5, GlaxoSmithKline, 5, GSK, 2, 5, Holds Patent mir-29 for the treatment of systemic sclerosis, 9, Inventiva, 2, 5, iQvia, 5, Italfarmaco, 2, 5, Italfarmco, 5, Lilly, 2, 5, med, 5, 8, medac, 5, Medac, 2, 5, MedImmune, 2, 5, Medscape, 5, 8, 9, Menarini, 8, Mepha, 8, Mitsubishi Tanabe, 2, 5, Mitsubishi Tanabe Pharma, 2, 5, MSD, 5, 8, Novartis, 2, 5, 8, 9, Patent, 9, Patent issued, 9, Pfizer, 2, 5, 8, Pharmacyclics, 2, 5, Roche, 5, 8, 9, Sanofi, 2, 5, Sinoxa, 2, 5, Target Bio Science, 5, Target BioScience, 5, UCB, 2, 5, 9, UCB in the area of potential treatments of scleroderma and its complications, 2, 5; R. Domsic, Boehringer Ingelheim, 5, Boehringer-Ingelheim, 5, Eicos, 5, EICOS Sciences Inc, 5; T. Doyle, Bristol-Myers Squibb, 2, Genentech, 2; P. Garcha, None; N. Gupta, None; A. Hoffmann-Vold, Actelion, 5, 8, Boehringer Ingelheim, 2, 5, 8, GSK, 5, 8; V. Hsu, None; F. Ingegnoli, None; K. Johannson, None; B. Kahaleh, None; L. Kawano-Dourado, Bristol-Myers-Squibb, 2, 5, Boehringer, 8, Roche, 8; E. Kazerooni, None; S. Khanna, None; P. Korsten, None; C. Lin, Genentech, 3; T. Maher, Boehringer Ingelheim, 5, 8; S. Mathai, None; F. Martinez, None; E. Matteson, Boehringer Ingelheim, 5, Pfizer, 2, Sun Pharmaceuticals, 2; V. Nagaraja, None; C. Oddis, None; J. Ovalles-Bonilla, None; J. Pauling, Boehringer Ingelheim, 5, Chugai Roche, 9; G. Raghu, Avalyn, 9, Bellerophan, 9, BI, 5, Biogen, 9, BMS, 9, Boehringer Ingelheim, 5, Bristol-Myers Squibb, 9, Fibrogen, 9, Gilead Sciences, 9, NIH, 2, Nitto, 9, Promedior, 9, Revistan, 9, Roche, 9, Roche/Genentech, 9, Roche-Genentech, 5, Sanofi, 9, Veracyte, 9; I. Rodriguez-Pinto, None; I. Rosas, None; J. Seibold, Boehringer Ingelheim, 5, Camurus AB, 5, Octapharma, 5, Corbus, 5, Bayer, 5, Indalo, 5, Blade, 5, Mitsubishi Tanabe Pharma, 5, Eicos Sciences, 5, Athersys, 4, Pacific Therapeutics, 4, BriaCell, 4; V. Steen, Boehringer Ingelheim, 5, Corbus, 5, 9, CSL, 5, 9, CSL Behring, 2, 5, DSMB, 5, 9, Galapagos, 5, 9; V. Strand, Abbvie, 5, AbbVie, 5, Amgen, 5, Amgen, Abbvie, Bayer, BMS, Boehringer Ingelheim, Celltrion, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, UCB, 5, AstraZeneca, 5, AURA, 8, Bayer, 5, BMS, 5, Boehringer Ingelheim, 5, Celgene, 5, Celltrion, 5, Cleveland Clinic, 8, CORRONA, 5, Crescendo, 5, Crescendo Bioscience, 5, Eli Lilly, 5, EMD Serono, 5, Genentech, 5, GlaxoSmithKline, 5, GSK, 5, Horizon, 5, Inmedix, 5, Janssen, 5, Kezar, 5, Lilly, 5, Merck, 5, NACCME, 8, Novartis, 5, Pfizer, 5, Purdue, 8, RA Forum, 8, RAN, 8, Regeneron, 5, Roche, 5, Samsung, 5, Sandoz, 5, Sanofi, 5, Servier, 5, Setpoint, 5, SLRA, 8, UCB, 5, Up to Date, 7, Washington University, 8, WIR, 8, WRA, 8; E. Volkmann, Boehringer Ingelheim, 5, Boehringer-Ingelheim, 5, Pfizer, 1, 4; D. Vummidi, None; S. Walsh, None; D. Zoz, Boehringer Ingelheim, 3, Boehringer Ingelheim Pharmaceuticals, 3; A. Wells, None; D. Khanna, Acceleron, 5, 8, Acceleron Pharma, 5, Actelion, 5, 8, Actelion Pharmaceuticals, 5, Astra Zeneca, 5, Bayer, 2, 5, 8, Behring, 5, Blade, 5, Blade Therapeutics, 5, 8, Blade therapeutics, 5, BMS, 2, 5, 8, Boehringer Ingelham, 5, Boehringer Ingelheim, 5, 8, Boehringer-Ingelheim, 5, Bristol Myers Squibb, 2, 5, Bristol-Myers Squibb, 2, 5, Celegene, 5, Celgene, 5, 8, ChemomAB, 5, ChemomAb, 5, CiviBioPharma, Inc., 3, Corbus, 5, Corobus, 5, Corpus, 5, CSL Behring, 5, 8, Curizon, 5, Curzion, 5, Cytori, 5, 8, Eicos, 4, Eicos Sciences, 4, Eicos Sciences, Inc, 4, Eicos Sciences, Inc/ CiviBioPharma, Inc, 1, 4, Eicos Sciences, Inc/ CiviBioPharma, Inc., 1, Eicos, Inc, 4, Eicos, Inc., 5, 8, Eicos, INC., 4, Galapagos, 5, Genentech, 5, Genentech/Roche, 5, GlaxoSmithKline, 5, GSK, 5, Horizon, 2, 5, Mitsubishi Tanabe Pharma, 5, Mitsubishi Tanabe Pharma Dev America, 5, Mitsubishi Tanabe Pharma Development America, 5, Mitsubishi Tanabi, 5, NIH K24 and R01, 2, NIH / NIAMS K24 AR-063120, 2, NIH/NIAMS R01& K24, 2, Pfizer, 2, 5, Sanofi, 5, Sanofi Aventis, 5, Sanofi-Aventis, 5, 8, Sanofi-Aventis/Genzyme, 5, UCB, 5, UCB Pharma, 5.

To cite this abstract in AMA style:

Roofeh D, Brown K, Tashkin D, Assassi S, Barratt S, Bernstein E, Bhatt N, Chung L, Collard H, Conway R, Dellaripa P, Denton C, Distler O, Domsic R, Doyle T, Garcha P, Gupta N, Hoffmann-Vold A, Hsu V, Ingegnoli F, Johannson K, Kahaleh B, Kawano-Dourado L, Kazerooni E, Khanna S, Korsten P, Lin C, Maher T, Mathai S, Martinez F, Matteson E, Nagaraja V, Oddis C, Ovalles-Bonilla J, Pauling J, Raghu G, Rodriguez-Pinto I, Rosas I, Seibold J, Steen V, Strand V, Volkmann E, Vummidi D, Walsh S, Zoz D, Wells A, Khanna D. Subsets in Systemic Sclerosis-ILD: Working Towards Consensus-Based Definitions [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/subsets-in-systemic-sclerosis-ild-working-towards-consensus-based-definitions/. Accessed January 30, 2023.

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