Impact of lung function and baseline clinical characteristics on patient-reported outcome measures in systemic sclerosis-associated interstitial lung disease

Michael Kreuter, Anna-Maria Hoffmann-Vold, Marco Matucci-Cerinic, Lesley Ann Saketkoo, Kristin B Highland, Hilary Wilson, Margarida Alves, Elvira Erhardt, Nils Schoof, Toby M Maher, Michael Kreuter, Anna-Maria Hoffmann-Vold, Marco Matucci-Cerinic, Lesley Ann Saketkoo, Kristin B Highland, Hilary Wilson, Margarida Alves, Elvira Erhardt, Nils Schoof, Toby M Maher

Abstract

Objective: The SENSCIS® trial demonstrated a significant reduction of lung function decline in patients with SSc-associated interstitial lung disease (SSc-ILD) treated with nintedanib, but no significant effect on health-related quality of life (HRQoL). To assess whether SSc/SSc-ILD severity and large changes in lung function correlate with HRQoL, a post-hoc analysis of SENSCIS®, aggregating treatment arms, was undertaken.

Methods: Patient-reported outcome (PRO) measures [St. George's Respiratory Questionnaire (SGRQ), Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnoea, and HAQ-Disability Index (HAQ-DI), incorporating the Scleroderma HAQ visual analogue scale (SHAQ VAS)] at baseline and week 52 were assessed for associations to SSc-ILD severity.

Results: At baseline and at week 52, forced vital capacity (FVC) <70% predicted was associated with worse PRO measure scores compared with FVC ≥70% predicted [week 52: SGRQ 45.1 vs 34.0 (P < 0.0001); FACIT-Dyspnoea 48.9 vs 44.5 (P < 0.0001); HAQ-DI 0.7 vs 0.6 (P < 0.0228); SHAQ VAS breathing problems 3.6 vs 2.6 (P < 0.0001)]. Patients with diffuse cutaneous SSc and other characteristics associated with SSc-ILD severity had worse PRO measure scores. Patients requiring oxygen or with >30% fibrosis on high-resolution computed tomography at baseline demonstrated worse PRO measure scores at week 52. After 1 year, patients with a major (>10%) improvement/worsening in FVC demonstrated corresponding improvement/worsening in SGRQ and other PRO measures, significant for the SGRQ symptom domain (P < 0.001).

Conclusion: Severe SSc-ILD and major deteriorations in lung function have important impacts on HRQoL. Treatments that slow lung function decline and prevent severe SSc-ILD are important to preserve HRQoL.

Trial registration: clinicaltrials.gov, www.clinicaltrials.gov, NCT02597933.

Keywords: SSc-associated ILD; patient-reported outcome measures; treatment.

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

Figures

Fig . 1
Fig. 1
PRO measures at week 52 in subgroups by FVC% predicted at week 52 The number of patients with data for PRO measures was variable, so a range is shown. FACIT: Functional Assessment of Chronic Illness Therapy; FVC: forced vital capacity; HAQ-DI: HAQ–Disability Index; PRO: patient-reported outcome; SGRQ: St. George's Respiratory Questionnaire; SHAQ VAS: Scleroderma HAQ visual analogue scale.
Fig . 2
Fig. 2
PRO measures at week 52 in subgroups by (A) supplemental oxygen use at baseline and (B) extent of fibrosis by HRCT at baseline The number of patients with data for PRO measures was variable, so a range is shown. FACIT: Functional Assessment of Chronic Illness Therapy; HAQ-DI: HAQ–Disability Index; HRCT: high-resolution CT; PRO: patient-reported outcome; SGRQ: St. George's Respiratory Questionnaire; SHAQ VAS: Scleroderma HAQ visual analogue scale.
Fig . 3
Fig. 3
Change in SGRQ scores at week 52 in patients with major, moderate or minor changes in FVC% predicted at week 52 Increasing SGRQ score represents deterioration in HRQoL. aThe number of patients with data within each change category was variable, depending on the measure, so a range is shown. FVC: forced vital capacity; HRQoL: health-related quality of life; SGRQ: St. George's Respiratory Questionnaire.

References

    1. Denton CP, Khanna D.. Systemic sclerosis. Lancet 2017;390:1685–99.
    1. Varga J, Trojanowska M, Kuwana M.. Pathogenesis of systemic sclerosis: recent insights of molecular and cellular mechanisms and therapeutic opportunities. J Scleroderma Relat Disord 2017;2:137–52.
    1. Nihtyanova SI, Denton CP.. Pathogenesis of systemic sclerosis associated interstitial lung disease. J Scleroderma Relat Disord 2020;5:6–16.
    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. Fretheim H, Halse AK, Seip M. et al. Multidimensional tracking of phenotypes and organ involvement in a complete nationwide systemic sclerosis cohort. Rheumatology 2020;59:2920–9.
    1. Elhai M, Meune C, Boubaya M. et al.; EUSTAR Group. Mapping and predicting mortality from systemic sclerosis. Ann Rheum Dis 2017;76:1897–905.
    1. Man A, Davidyock T, Ferguson LT. et al. Changes in forced vital capacity over time in systemic sclerosis: application of group-based trajectory modelling. Rheumatology 2015;54:1464–71.
    1. Steen VD, Conte C, Owens GR, Medsger TA. Jr. Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum 1994;37:1283–9.
    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, Alves M. et al. 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. Saketkoo LA, Mittoo S, Huscher D. et al. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials. Thorax 2014;69:428–36.
    1. Pauling JD, Caetano J, Campochiaro C. et al. Patient-reported outcome instruments in clinical trials of systemic sclerosis. J Scleroderma Relat Disord 2020;5:90–102.
    1. Kreuter M, Swigris J, Pittrow D. et al. Health related quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF registry. Respir Res 2017;18:139.
    1. Yount SE, Beaumont JL, Chen S-Y. et al. Health-related quality of life in patients with idiopathic pulmonary fibrosis. Lung 2016;194:227–34.
    1. Olson AL, Brown KK, Swigris JJ.. Understanding and optimizing health-related quality of life and physical functional capacity in idiopathic pulmonary fibrosis. Patient Relat Outcome Meas 2016;7:29–35.
    1. Kreuter M, Swigris J, Pittrow D. et al. The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry. Respir Res 2019;20:59.
    1. Khanna D, Clements PJ, Furst DE. et al. 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. Tashkin DP, Volkmann ER, Tseng C-H. 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. Saketkoo LA, Scholand MB, Lammi MR, Russell A-M.. Patient-reported outcome measures in systemic sclerosis-related interstitial lung disease for clinical practice and clinical trials. J Scleroderma Relat Disord 2020;5:48–60.
    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. 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.
    1. European Medicines Agency [Internet]. OFEV® (nintedanib): Summary of Product Characteristics; [updated January 25, 2021]. (11 June 2021, date last accessed).
    1. U.S. Food & Drug Administration [Internet]. OFEV® (nintedanib): prescribing information; [updated October 28, 2020]. (11 June 2021, date last accessed).
    1. Boehringer Ingelheim [Internet]. FDA approves Ofev® as first treatment for chronic fibrosing ILDs with a progressive phenotype. (17 September 2021, date last accessed).
    1. Distler O, Highland KB, Gahlemann M. et al. Nintedanib for systemic sclerosis–associated interstitial lung disease. N Engl J Med 2019;380:2518–28.
    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. Ryerson CJ, O'Connor D, Dunne JV. et al. Predicting mortality in systemic sclerosis-associated interstitial lung disease using risk prediction models derived from idiopathic pulmonary fibrosis. Chest 2015;148:1268–75.
    1. Kafaja S, Clements PJ, Wilhalme H. et al. Reliability and minimal clinically important differences of forced vital capacity: Results from the Scleroderma Lung Studies (SLS-I and SLS-II). Am J Respir Crit Care Med 2018;197:644–52.
    1. Goh NS, Hoyles RK, Denton CP. et al. Short-term pulmonary function trends are predictive of mortality in interstitial lung disease associated with systemic sclerosis. Arthritis Rheumatol 2017;69:1670–8.
    1. Hoffmann-Vold A-M, 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. 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. Khanna D, Lin CJF, Furst DE. et al. Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2020;8:963–74.
    1. Spiera RF, Gordon JK, Mersten JN. et al. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis 2011;70:1003–9.
    1. Richeldi L, Cottin V, du Bois RM. et al. Nintedanib in patients with idiopathic pulmonary fibrosis: combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med 2016;113:74–9.
    1. Christmann RB, Wells AU, Capelozzi VL, Silver RM.. Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin Arthritis Rheum 2010;40:241–9.
    1. Jones PW. St. George's Respiratory Questionnaire: CID. COPD 2005;2:75–9.
    1. Racine M, Hudson M, Baron M, Nielson WR; Canadian Scleroderma Research Group. The impact of pain and itch on functioning and health-related quality of life in systemic sclerosis: an exploratory study. J Pain Symptom Manage 2016;52:43–53.
    1. Enck P, Klosterhalfen S.. Placebos and the placebo effect in drug trials. Handb Exp Pharmacol 2019;260:399–431.

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