Michael B Arnold1, Dinesh Khanna2, Christopher P Denton3, Jacob M van Laar4, Tracy M Frech5, Marina E Anderson6, Murray Baron7, Lorinda Chung8, Gerhard Fierlbeck9, Santhanam Lakshminarayanan10, Yannick Allanore11, Gabriela Riemekasten12, Virginia Steen13, Ulf Müller-Ladner14, Helen Spotswood15, Laura Burke15, Jeffrey Siegel16, Angelika Jahreis16, Daniel E Furst17, Janet E Pope1. 1. Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. 2. Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, USA. 3. Rheumatology and Connective Tissue Diseases, University College London Medical School, London, UK. 4. Rheumatology & Clinical Immunology, University of Utrecht, Utrecht, The Netherlands. 5. Rheumatology, University of Utah, Veterans Affairs Medical Center, Salt Lake City, UT, USA. 6. Rheumatology, University of Liverpool and Aintree University Hospital, Liverpool, UK. 7. Rheumatology, Jewish General Hospital, Montreal, QC, Canada. 8. Medicine and Dermatology, Stanford University School of Medicine and Palo Alto VA Health Care System, Palo Alto, CA, USA. 9. Dermatology, University of Tubingen, Tubingen, Germany. 10. Rheumatology, University of Connecticut Health Center, Farmington, CT, USA. 11. Rheumatology, Paris Descartes University, Paris, France. 12. Rheumatology, Charité University Hospital, German Rheumatism Research Center, Berlin, Germany. 13. Rheumatology, Georgetown University, Washington, DC, USA. 14. Lehrstuhl für Innere Medizin mit Schwerpunkt Rheumatologie, Justus-Liebig University Giessen, Kerckhoff Clinic, Bad Nauheim, Germany. 15. Roche Products Ltd, Welwyn Garden City, UK. 16. Rheumatology and Rare Diseases, Genentech, South San Francisco. 17. Rheumatology, University of California, Los Angeles, CA, USA.
Abstract
Objectives: Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo. Methods: Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks. Three different types of PASS questions were evaluated at weeks 8, 24, 48 and 96, including if a current state would be acceptable over time as a yes vs no response and Likert scales about how acceptable a current state is if remaining over time. Additional outcomes assessed included modified Rodnan skin score, HAQ disability index (HAQ-DI), physician and patient global assessments on a visual analogue scale, CRP and ESR. Results: The placebo group consisted of 44 patients and the TCZgroup had 43 patients. At baseline, 33% achieved a PASS for all three PASS questions, with the proportion increasing to 69, 71 and 78%, respectively, at 96 weeks. Changes in PASS scores showed a moderately negative correlation with HAQ-DI and patient and physician global assessments visual analogue scales, which indicates expected improvements as PASS improved. The PASS question, 'Considering all of the ways your scleroderma has affected you, how acceptable would you rate your level of symptoms?' showed significant correlations with patient-reported outcomes and differentiating placebo vs TCZ at 48 weeks (P = 0.023). Conclusion:PASS may be used as a patient-centred outcome in SSc, especially as a 7-point Likert scale. Further validation is required to determine the utility as an outcome measure in trials and clinical practice.
RCT Entities:
Objectives:Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo. Methods: Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks. Three different types of PASS questions were evaluated at weeks 8, 24, 48 and 96, including if a current state would be acceptable over time as a yes vs no response and Likert scales about how acceptable a current state is if remaining over time. Additional outcomes assessed included modified Rodnan skin score, HAQ disability index (HAQ-DI), physician and patient global assessments on a visual analogue scale, CRP and ESR. Results: The placebo group consisted of 44 patients and the TCZ group had 43 patients. At baseline, 33% achieved a PASS for all three PASS questions, with the proportion increasing to 69, 71 and 78%, respectively, at 96 weeks. Changes in PASS scores showed a moderately negative correlation with HAQ-DI and patient and physician global assessments visual analogue scales, which indicates expected improvements as PASS improved. The PASS question, 'Considering all of the ways your scleroderma has affected you, how acceptable would you rate your level of symptoms?' showed significant correlations with patient-reported outcomes and differentiating placebo vs TCZ at 48 weeks (P = 0.023). Conclusion: PASS may be used as a patient-centred outcome in SSc, especially as a 7-point Likert scale. Further validation is required to determine the utility as an outcome measure in trials and clinical practice.
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