Background/Purpose: RA is associated with significant pulmonary comorbidity and declines in lung function over time; but longitudinal assessment of pulmonary abnormalities in the context of RA treatment needs further characterization. Mavrilimumab, an investigational human monoclonal antibody, inhibits GM-CSF by binding to the GM-CSF receptor α subunit. We investigated pulmonary safety of mavrilimumab because of its potential to inhibit alveolar macrophage function.

Methods: Pulmonary monitoring included standardized lung function testing (spirometry and diffusing capacity of lung carbon monoxide [DLCO]), chest X-rays, assessments of dyspnea and pulmonary adverse events (AEs) in two randomized, double-blind, multicenter studies (NCT01706926; NCT01715896) where pts with moderate to severe RA received mavrilimumab or placebo and mavrilimumab or golimumab, respectively, and the long-term open-label extension (NCT01712399) where all received mavrilimumab. All studies excluded pts with clinically significant uncontrolled pulmonary disease. Adjudication of lung function abnormalities and pulmonary AEs was by an Independent Pulmonary Expert Committee.

Results: The 442 pts receiving mavrilimumab had cumulative safety data exposure of approximately 900 pt-yrs and median (min–max) exposure of 2.5 (0.1–3.3) yrs. Baseline (BL) characteristics are shown in the Table. Mean forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), DLCO (Figure), and dyspnea (Table) were mostly maintained within 5% of BL values for pts treated during the randomized phases of NCT01706926 and NCT01715896. Few pts showed clinically significant (>20% from BL and <80% predicted) decreases in predicted FEV₁ and FVC (Table); these were mostly transient. Overall, 83 pts (9.24/100 pt-yrs) reported ≥1 pulmonary AE; bronchitis was reported most frequently (pts [per 100 pt-yrs]: 34 [3.78]), followed by respiratory tract infection and cough (14 [1.56] and 12 [1.34], respectively). The rate of pulmonary AEs reported was generally stable over time. No suspected/confirmed pulmonary alveolar proteinosis cases, no pulmonary-related deaths, and only one treatment-related pulmonary serious AE (acute bronchitis) were reported.

Conclusion: Many pts with BL pulmonary comorbidities were identified. Mavrilimumab was not associated with substantial effects on pulmonary function; the rate of pulmonary AEs was stable during the study. This may be the most comprehensive longitudinal study of pulmonary function in RA; further long-term studies should fully characterize these findings and any impact of therapies. ^Joint senior authors.