Roflumilast (Daliresp®) to reduce acute pulmonary events in fibrotic sarcoidosis: a multi-center, double blind, placebo controlled, randomized clinical trial

Robert P Baughman, Marc A Judson, Daniel A Culver, Surinder S Birring, Joseph Parambil, Joyce Zeigler, Elyse E Lower, Robert P Baughman, Marc A Judson, Daniel A Culver, Surinder S Birring, Joseph Parambil, Joyce Zeigler, Elyse E Lower

Abstract

Background: Fibrotic sarcoidosis patients often have acute events of increased cough and sputum production. We evaluated the impact of roflumilast in fibrotic sarcoidosis patients with repeated episodes of increased cough and sputum.

Methods: Sarcoidosis patients with pulmonary fibrosis and at least two acute episodes in the previous year were randomized to receive either roflumilast (ROF) or placebo (PLA) in a double blind, placebo controlled multi-center trial. Subjects were assessed initially and every three months for 12 months. At each visit, spirometry and health related quality of life questionnaires were completed. For each subject, the best forced expiratory volume at 1 second (FEV-1) was noted.

Results: Of the 38 subjects who enrolled in the study, 28 subjects (14 in each group) received at least three months of treatment and 10 in each arm completing all 12 months of study. During the treatment, patients treated with ROF were less likely to have visits in which the FEV-1 was less than 90% of the best FEV-1 (Odds ratio=0.34 (0.16 to 0.76 95% confidence interval, p=0.0073). At the end of treatment with ROF, patients had a significant improvement in their KSQ LUNG (Initial visit: 45.3 ± 6.89 (Mean ± S.D.); Last visit: 52.6± 7.91, p<0.05) with no change for PLA treated patients.

Conclusion: Patients treated with at least three months of roflumilast had fewer follow-up visits with an FEV-1 of less than 90% of best value. At the end of treatment, ROF treated patients had a better quality of life as assessed by KSQ LUNG.

Clinical trial registration: NCT01830959.

Keywords: fibrotic sarcoidosis; quality of life; roflumilast; spirometry.

Conflict of interest statement

RPB had full access to all the data in the study and takes responsibility for the content of the manuscript, including the data and analysis. RPB, EEL, MAJ, and DAC contributed substantially to study design. RPB, MAJ, DAC, JP, JZ, and EEL contributed substantially to data acquisition. RPB, SB, EEL, MAJ, and DAL contributed substantially to data analysis, interpretation, and writing of the manuscript Financial/nonfinancial disclosures: Astra Zeneca and NIH provided grant support for this study Astra Zeneca provided an unrestricted grant and provided drug. They had no role in study design, data analysis, interpretation, or writing of the manuscript.

Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.

Figures

Figure 1.
Figure 1.
CONSORT (31) diagram of patients enrolled in study. Of the original 37 patients who enrolled in the study, 28 took at least three months of therapy (grey box) and 20 completed the full twelve months of treatment. Analysis was performed on the 28 patients who received at least three months of therapy.
Figure 2.
Figure 2.
Values for initial and end of visit. At the end of treatment, the KSQ LUNG increased by more than 7 points in the ROF group (Figure 2A, p

Figure 3.

Values for initial and end…

Figure 3.

Values for initial and end of treatment visit. At the end of treatment,…

Figure 3.
Values for initial and end of treatment visit. At the end of treatment, there was borderline significant improvement in the LCQ for the ROF patients (Figure 3A, p=0.07), but not for the PLA patients (Figure 3B). Bar indicates mean value for each timeperiod.
Figure 3.
Figure 3.
Values for initial and end of treatment visit. At the end of treatment, there was borderline significant improvement in the LCQ for the ROF patients (Figure 3A, p=0.07), but not for the PLA patients (Figure 3B). Bar indicates mean value for each timeperiod.

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