Dyspnoea and cough in patients with systemic sclerosis-associated interstitial lung disease in the SENSCIS trial

Elizabeth R Volkmann, Michael Kreuter, Anna M Hoffmann-Vold, Marlies Wijsenbeek, Vanessa Smith, Dinesh Khanna, Christopher P Denton, Wim A Wuyts, Corinna Miede, Margarida Alves, Steven Sambevski, Yannick Allanore, Elizabeth R Volkmann, Michael Kreuter, Anna M Hoffmann-Vold, Marlies Wijsenbeek, Vanessa Smith, Dinesh Khanna, Christopher P Denton, Wim A Wuyts, Corinna Miede, Margarida Alves, Steven Sambevski, Yannick Allanore

Abstract

Objective: The aim of these analyses was to investigate the rate of decline in forced vital capacity (FVC) in patients with SSc-associated interstitial lung disease (SSc-ILD) with and without cough or dyspnoea in the SENSCIS trial.

Methods: Patients in the SENSCIS trial were randomized to receive nintedanib or placebo. Subgroups with and without cough or dyspnoea at baseline were defined by responses to the St George's Respiratory Questionnaire.

Results: At baseline, 114/575 patients (19.8%) did not have cough and 172/574 patients (30.0%) did not have dyspnoea. In the placebo group, the rate of FVC decline over 52 weeks was similar in patients with and without cough (-95.6 and -83.4 mL/year, respectively) or dyspnoea (-95.8 and -87.7 mL/year, respectively). The effect of nintedanib vs placebo on reducing the rate of FVC decline was numerically more pronounced in patients without than with cough [difference: 74.4 (95% CI -11.1, 159.8) vs 31.5 (-11.1, 74.1)] and without than with dyspnoea [79.8 (9.8, 149.7) vs 25.7 (-19.9, 71.3)], but interaction P-values did not indicate heterogeneity in the treatment effect between these subgroups (P = 0.38 and P = 0.20, respectively).

Conclusion: In the placebo group of the SENSCIS trial, the rate of FVC decline was similar irrespective of the presence of cough or dyspnoea at baseline. The effect of nintedanib on reducing the rate of FVC decline was numerically more pronounced in patients without than with cough or dyspnoea at baseline, but no statistically significant heterogeneity was observed between the subgroups.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT02597933" title="See in ClinicalTrials.gov">NCT02597933.

Keywords: connective tissue diseases; nintedanib; systemic scleroderma; vital capacity.

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Rate of decline in FVC (mL/year) over 52 weeks in subgroups by respiratory symptoms at baseline in the SENSCIS trial Rate of decline in FVC (mL/year) over 52 weeks in subgroups by (A) cough at baseline, (B) dyspnoea at baseline, and (C) both cough and dyspnoea, cough only or dyspnoea only, or neither cough nor dyspnoea. FVC, forced vital capacity.

References

    1. van den Hoogen F, Khanna D, Fransen J. et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737–47.
    1. Hoffmann-Vold AM, Fretheim H, Halse AK. et al. Tracking impact of interstitial lung disease in systemic sclerosis in a complete nationwide cohort. Am J Respir Crit Care Med 2019;200:1258–66.
    1. Faisal A, Alghamdi BJ, Ciavaglia CE. et al. Common mechanisms of dyspnea in chronic interstitial and obstructive lung disorders. Am J Respir Crit Care Med 2016;193:299–309.
    1. Cheng JZ, Wilcox PG, Glaspole I. et al. Cough is less common and less severe in systemic sclerosis–associated interstitial lung disease compared to other fibrotic interstitial lung diseases. Respirology 2017;22:1592–7.
    1. Tashkin DP, Volkmann ER, Tseng CH. et al. Improved cough and cough-specific quality of life in patients treated for scleroderma-related interstitial lung disease: results of Scleroderma Lung Study II. Chest 2017;151:813–20.
    1. Birring SS, Kavanagh JE, Irwin RS. et al.; Collaborators. Treatment of interstitial lung disease associated cough: CHEST guideline and expert panel report. Chest 2018;154:904–17.
    1. Hu S, Hou Y, Wang Q. et al. Prognostic profile of systemic sclerosis: analysis of the clinical EUSTAR cohort in China. Arthritis Res Ther 2018;20:235.
    1. Khanna D, Clements PJ, Furst DE. et al.; for the Scleroderma Lung Study Group. Correlation of the degree of dyspnea with health-related quality of life, functional abilities, and diffusing capacity for carbon monoxide in patients with systemic sclerosis and active alveolitis: results from the Scleroderma Lung Study. Arthritis Rheum 2005;52:592–600.
    1. Baron M, Sutton E, Hudson M. et al. The relationship of dyspnoea to function and quality of life in systemic sclerosis. Ann Rheum Dis 2008;67:644–50.
    1. Theodore AC, Tseng CH, Li N. et al. Correlation of cough with disease activity and treatment with cyclophosphamide in scleroderma interstitial lung disease: findings from the Scleroderma Lung Study. Chest 2012;142:614–21.
    1. Kahrilas PJ, Altman KW, Chang AB. et al. Chronic cough due to gastroesophageal reflux in adults: CHEST guideline and expert panel report. Chest 2016;150:1341–60.
    1. Li Q, Wallace L, Patnaik P, Alves M. et al. Disease frequency, patient characteristics, comorbidity outcomes and immunosuppressive therapy in systemic sclerosis and systemic sclerosis–associated interstitial lung disease: a US cohort study. Rheumatology (Oxford) 2021;60:1915–25.
    1. Irwin RS, French CL, Chang AB. et al. CHEST Expert Cough Panel. Classification of cough as a symptom in adults and management algorithms: CHEST guideline and expert panel report. Chest 2018;153:196–209.
    1. Shim J, Song W, Morice AH.. Drug-induced cough. Physiol Res 2020;69:S81–92.
    1. Vacca A, Meune C, Gordon J. et al.; Scleroderma Clinical Trial Consortium Cardiac Subcommittee. Cardiac arrhythmias and conduction defects in systemic sclerosis. Rheumatology (Oxford) 2014;53:1172–7.
    1. Galiè N, Humbert M, Vachiery JL. et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015;46:903–75.
    1. Steen VD, Conte C, Owens GR, Medsger TA Jr.. Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum 1994;37:1283–9.
    1. Adler S, Huscher D, Siegert E. et al.; EUSTAR co-workers on behalf of the DeSScipher project research group within the EUSTAR network. Systemic sclerosis associated interstitial lung disease – individualized immunosuppressive therapy and course of lung function: results of the EUSTAR group. Arthritis Res Ther 2018;20:17.
    1. Forestier A, Le Gouellec N, Béhal H. et al. Evolution of high-resolution CT-scan in systemic sclerosis–associated interstitial lung disease: description and prognosis factors. Semin Arthritis Rheum 2020;50:1406–13.
    1. Distler O, Highland KB, Gahlemann M. et al.; SENSCIS Trial Investigators. Nintedanib for systemic sclerosis–associated interstitial lung disease. N Engl J Med 2019;380:2518–28.
    1. Maher TM, Mayes MD, Kreuter M. et al.; SENSCIS Trial Investigators. Effect of nintedanib on lung function in patients with systemic sclerosis–associated interstitial lung disease: further analyses of a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol 2021;73:671–6.
    1. Nishiyama O, Taniguchi H, Kondoh Y. et al. A simple assessment of dyspnoea as a prognostic indicator in idiopathic pulmonary fibrosis. Eur Respir J 2010;36:1067–72.
    1. du Bois RM, Weycker D, Albera C. et al. Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;184:459–66.
    1. Ryerson CJ, Abbritti M, Ley B. et al. Cough predicts prognosis in idiopathic pulmonary fibrosis. Respirology 2011;16:969–75.
    1. Case AH, Hellkamp AS, Neely ML. et al. Associations between patient-reported outcomes and death or lung transplant in idiopathic pulmonary fibrosis. Data from the Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry. Ann Am Thorac Soc 2020;17:699–705.
    1. Jones PW, Quirk FH, Baveystock CM.. The St George’s Respiratory Questionnaire. Respir Med 1991;85:25–31.
    1. Swigris JJ, Wilson H, Esser D. et al. Psychometric properties of the St George's Respiratory Questionnaire in patients with idiopathic pulmonary fibrosis: insights from the INPULSIS trials. BMJ Open Respir Res 2018;5:e000278.
    1. Hoffmann-Vold AM, Maher TM, Philpot EE. et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol 2020;2:E71–83.
    1. Perelas A, Silver RM, Arrossi AV, Highland KB.. Systemic sclerosis–associated interstitial lung disease. Lancet Respir Med 2020;8:304–20.
    1. Roofeh D, Lescoat A, Khanna D.. Treatment for systemic sclerosis–-associated interstitial lung disease. Curr Opin Rheumatol 2021;33:240–8.
    1. Hoffmann-Vold AM, Allanore Y, Alves M. et al.; EUSTAR collaborators. Progressive interstitial lung disease in patients with systemic sclerosis–associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis 2021;80:219–27.
    1. Volkmann ER. Natural history of systemic sclerosis–related interstitial lung disease: how to identify a progressive fibrosing phenotype. J Scleroderma Relat Disord 2020;5:31–40.
    1. Hoffmann-Vold AM, Allanore Y, Bendstrup E. et al. The need for a holistic approach for SSc-ILD – achievements and ambiguity in a devastating disease. Respir Res 2020;21:197.
    1. Parshall MB, Schwartzstein RM, Adams L. et al.; American Thoracic Society Committee on Dyspnea. An official American Thoracic Society Statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 2012;185:435–52.
    1. Volkmann ER, Tashkin DP, LeClair H. et al. Treatment with mycophenolate and cyclophosphamide leads to clinically meaningful improvements in patient-reported outcomes in scleroderma lung disease: results of Scleroderma Lung Study II. ACR Open Rheumatol 2020;2:362–70.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere