Rituximab in the Treatment of Interstitial Lung Disease Associated with Antisynthetase Syndrome: A Multicenter Retrospective Case Review

Abstract

Objective: To assess clinical outcomes including imaging findings on computed tomography (CT), pulmonary function testing (PFT), and glucocorticoid (GC) use in patients with the antisynthetase syndrome (AS) and interstitial lung disease (ILD) treated with rituximab (RTX).

Methods: We retrospectively identified all patients at 2 institutions with AS-ILD who were treated with RTX. Baseline demographics, PFT, and chest CT were assessed before and after RTX. Two radiologists independently evaluated CT using a standardized scoring system.

Results: Twenty-five subjects at the Brigham and Women's Hospital (n = 13) and University of Pittsburgh Medical Center (n = 12) were included. Antisynthetase antibodies were identified in all patients (16 Jo1, 6 PL-12, 3 PL-7). In 21 cases (84%), the principal indication for RTX use was recurrent or progressive ILD, owing to failure of other agents. Comparing pre- and post-RTX pulmonary variables at 12 months, CT score and forced vital capacity were stable or improved in 88% and 79% of subjects, respectively. Total lung capacity (%) increased from 56 ± 13 to 64 ± 13 and GC dose decreased from 18 ± 9 to 12 ± 12 mg/day. Although DLCO (%) declined slightly at 1 year, it increased from 42 ± 17 to 70 ± 20 at 3 years. The most common imaging patterns on CT were nonspecific interstitial pneumonia (NSIP; n = 13) and usual interstitial pneumonia/fibrotic NSIP (n = 5), of which 5 had concurrent elements of cryptogenic organizing pneumonia.

Conclusion: Stability or improvement in pulmonary function or severity of ILD on CT was seen in most patients. Use of RTX was well tolerated in the majority of patients. RTX may play a therapeutic role in patients with AS-ILD, and further clinical investigation is warranted.

Keywords: ANTISYNTHETASE SYNDROME; INTERSTITIAL LUNG DISEASE; RITUXIMAB.

Figure 1. CT scan before and after treatment with Rituximab for BWH Subject 2

Pre-Rituximab (CT score 125.1) – Axial HRCT images in lung windows (A + B) demonstrate subpleural reticulation, coarse linear bands, groundglass abnormality and patchy consolidation within the lower lobes, lingula and right middle lobe in a predominantly peripheral, subpleural distribution. Affected areas of lung demonstrate traction bronchiectasis and architectural distortion. No honeycombing was present, and lung volumes were mildly reduced. Pattern of interstitial pneumonitis has overlapping features of both non-specific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia (COP). >3-years Post-Rituximab (CT score 113.7) – Axial HRCT images (C + D) in lung windows demonstrates definite improvement in bilateral subpleural reticulation, consolidation and architectural distortion. Residual groundglass opacity is present with subpleural sparing, imaging features are consistent with a milder non-specific interstitial pneumonia (NSIP) pattern.

Figure 2. Graph of CT score (A) and forced vital capacity percent predicted (FVC%) (B) by subject over 3 years of follow-up

2A: Line graph of CT scores demonstrating stability or improvement (decrease in CT score) in ≥75% of subjects over the 3 years of follow-up. 2B: Line graph of FVC% demonstrating stability or improvement in ≥79% of subjects over the 3 years of follow-up.