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

Abstract

Objective To investigate the rate of decline in forced vital capacity (FVC) in patients with systemic sclerosis-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://clinicaltrials.gov, NCT02597933

Effect of Nintedanib in Patients with Progressive Pulmonary Fibrosis in Subgroups with Differing Baseline Characteristics

“…No heterogeneity was detected in the effect of nintedanib on reducing the rate of FVC decline across subgroups based on demographics (age, sex, race, BMI), measures of disease severity (FVC, DLco, CPI, GAP stage, time since diagnosis of ILD), or use of anti-acid therapy or DMARDs at baseline. These findings are in line with the consistent effect of nintedanib across subgroups based on baseline characteristics observed in clinical trials in patients with IPF [ 18 – 25 ] and SSc-ILD [ 26 – 30 ]. Previous analyses of data from the INBUILD trial also found no heterogeneity in the effect of nintedanib across five subgroups by ILD diagnosis (hypersensitivity pneumonitis, autoimmune ILDs, iNSIP, unclassifiable IIP, other ILDs) [ 31 ] or among subgroups with ILD associated with rheumatoid arthritis, SSc, mixed connective tissue disease, or other autoimmune diseases [ 32 ].…”

Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease

“…Despite this, ∼30% of these patients did not have dyspnoea and 20% did not have cough. This finding, which is consistent with analyses of the overall trial population [ 20 ], highlights that respiratory symptoms may be a late presentation of SSc-ILD, and supports the screening of all patients with SSc for ILD at diagnosis, including those with lcSSc and without respiratory symptoms, as recommended by experts [ 21 ].…”

Clinical Predictors of Lung-Function Decline in Systemic-Sclerosis-Associated Interstitial Lung Disease Patients with Normal Spirometry

“…According to our data, SSc patients with HRCT-confirmed ILD who are experiencing cough as the leading respiratory symptom might be at higher risk of developing PPF even with normal lung function results when presented at the respiratory specialist. Similarly, cough was also studied in a subgroup analysis of the SENSCIS trial and was found to be an important prognostic factor for functional decline and progression in SSc-ILD patients [ 17 ]. However, patients enrolled in the SENSCIS trial had less preserved lung function and patients with cough had an average decline of −95.6 mL/year, which was slightly higher than in our study.…”