In patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD), severe gastroesophageal reflux disease (GERD) symptoms were associated with future radiographic ILD progression, even in patients using proton pump inhibitors (PPI), according to study results published in Arthritis Care & Research.
Reflux and other symptoms of esophageal involvement affect 90% of patients with SSc, often worsening as the disease progresses. To clarify the relationship between GERD and ILD progression in SSc, researchers sought to investigate the relationship between increased GERD symptoms and worsening SSc-ILD.
The current study involved participants and data from Scleroderma Lung Study II (SLSII; ClinicalTrials.gov Identifier: NCT00883129), a multicenter, randomized controlled trial that compared the benefits of treating SSc-ILD with mycophenolate mofetil for 2 years vs cyclophosphamide for 1 year. As a part of outcomes measurement, SLSII assessed patients’ 2-year change in quantitative lung fibrosis (QLF) and total quantitative extent of ILD (QILD) in both the whole lung (WL) and lobe of maximum involvement (LM).
Notably, SLSII also prospectively collected patient-reported outcome data that included data on gastrointestinal symptoms; the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 was used to assess the severity of SSc-related gastrointestinal tract symptoms at baseline. Trial investigators also obtained high-resolution computed tomography (HRCT) images of the chest that offered the ability to measure esophageal dilation.
The current analysis investigated the association between SSc-ILD and GERD progression by correlating baseline data from patient symptom reports and esophageal dilation images with data on patients’ pulmonary changes after 2 years. Participants included adults with SSc (aged ≥18 years) and a disease duration of 7 years or less from onset of the first non-Raynaud symptom attributable to SSc. A total of 142 patients (74% women; mean age, 52 years; mean disease duration, 2.6 years) were included; of these, 76% (n=107) were taking a PPI at baseline.
The baseline mean patient-reported reflux scale score was 0.57 (n=141), which indicated moderate reflux. The baseline mean maximal esophageal diameter and area were 22 (SD 8.16; range, 6.30-51.60) mm and 242 (SD 161.07; range, 20.60-906.59) mm2, respectively (n=121). Patients’ baseline reflux score was positively correlated with a change in QLF-LM (regression coefficient 5.51; P =.0046) and QLF-WL (regression coefficient β, 2.09; P = .0063) at 2 years. The baseline reflux score was also associated with change in QILD-LM (regression coefficient, 3.72; P =.076) and QILD-WL (regression coefficient 2.61; P = .11) at 2 years, although the associations did not meet the predefined threshold for statistical significance (P <.05). The esophageal diameter and area were not significantly associated with a change in QLF-WL and QILD-WL or with QLF-LM or QILD-LM at 2 years (all P-values ≥0.2).
Multivariable analysis demonstrated the reflux score was positively associated with a change in QLF-LM (estimate 5.63; P =.007) and QLF-WL (estimate 2.19; P = .005) at 2 years, after adjustment for baseline QLF score, treatment arm, and PPI use. The patients’ baseline reflux score also was associated with a change in QILD-WL (estimate 3.45; P =.039) at 2 years, after adjustment for baseline QILD score, treatment arm, and PPI use.
No significant associations between PPI use, high-dose PPI use, changes in QLF or QILD or between esophageal diameter and area, and changes in QLF or QILD were found. Additionally, there was no significant interaction observed between the patients’ reflux score and PPI use.
Notably, the baseline reflux score was not independently associated with the course of FVC percentage predicted at 24 months (P =.72), nor was PPI use (P =.63) in the joint model analysis.
Study limitations include possible inadequate amount of power to detect significant differences in ILD progression based on PPI use, a possible inconsistent PPI dosing schedule, and lack of a functional measure of esophageal involvement, such as manometry. In addition, confounding factors that could affect the primary outcome are likely.
“The findings of the present study suggest that patient-reported symptoms of GERD are
associated with future SSc-ILD progression. Optimizing the treatment of GERD may lead
to improved outcomes in patients with SSc-ILD,” study authors concluded.
Disclosure: Hoffmann-LaRoche supplied mycophenolate mofetil for use in Scleroderma Lung Study II. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Volkmann ER, Tashkin DP, Leng M, et al. Association of symptoms of gastroesophageal reflux, esophageal dilation and progression of systemic sclerosis-related interstitial lung disease. Arthritis Care Res (Hoboken). Published online December 12, 2022. doi:10.1002/acr.25070