Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue diseases (CTD). CTD-related ILD (CTD-ILD) has typically been treated with mycophenolate mofetil (MMF) and cyclophosphamide. B-cell depletion therapy with rituximab is increasingly being used in CTD-ILD based on the concept that B cells play a key role in the inflammatory process. The goal of this study was to compare the effect of rituximab versus MMF on pulmonary function in patients with CTD-ILD.
Methods: The study was conducted at two sites, Stanford and Centre Hospitalier de l’Universite de Montreal. Retrospective chart review was performed on 83 subjects; the 15 patients in the treatment group received rituximab ± MMF (10/15 received both), and the 68 patients in the control group received MMF only. All had documented ILD and met validated classification criteria for a specific CTD, including systemic sclerosis (n=26), dermatomyositis/polymyositis (16), rheumatoid arthritis (15), Sjogren’s syndrome (12), mixed connective tissue disease (8), and undifferentiated connective tissue disease (6). The difference in predicted forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) at baseline and after 6-12 months of therapy was compared between the treatment group and control group by Wilcoxon rank-sum test. Linear mixed models accounting for repeated measures assessed for changes in PFTs over time. Kaplan-Meier estimates compared survival between groups.
Results: There were no significant differences in age, gender, ethnicity, baseline FVC, presence of pulmonary hypertension, or concurrent use of other immunosuppressive medications. However ILD duration prior to treatment initiation was longer in the treatment group at 47 months (range 4-170 months) versus 6.5 months (range 0-164 months) in the control group (p=0.0003). Baseline DLCO was numerically lower in the treatment group at 51.5% (range 28-76%) versus 62.0% (range 27-116%, p=0.058) in the control group. Wilcoxon rank-sum testing revealed a 3.5% (range -11-21%) decrease in FVC in the treatment group compared to a 2.0% (range -14-25%) increase in the control group (p=0.029), and a 3.0% (range -10-12%) decrease in DLCO in the treatment group compared to a 4.5% (range -30-36%) increase in the control group (p=0.046).
Mixed model analysis controlling for ILD disease duration at treatment initiation, baseline DLCO, SSc vs. non-SSc, presence of pulmonary hypertension, and use of prednisone showed no significant difference in FVC between groups at 6 months (-1.77 (95% CI -10.25-6.72), p=0.70) and 1 year (-3.06 (95% CI -11.59-5.46), p=0.48). There was a non-significant decrease in DLCO in the treatment compared to control group at 6 months (-4.58 (95% CI -10.28-1.12), p=0.11), and a significant decrease at 1 year (-6.20 (95% CI -11.97–0.43), p=0.04). The all-cause mortality rate was 2/15 in the treatment group and 6/68 in the control group, with 1, 2, and 3 year survival rates of 100%, 100%, and 89% vs. 99%, 94%, and 92%, respectively (p=0.45).
Conclusion: Rituximab ± MMF did not improve pulmonary function, but resulted in similar survival compared to MMF alone in a recalcitrant population of CTD-ILD.
To cite this abstract in AMA style:Zhu L, Li S, Gagne L, Jacobs S, Morisset J, Mooney J, Raj R, Chung L. Rituximab Versus Mycophenolate Mofetil in Interstitial Lung Disease Secondary to Connective Tissue Disease [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/rituximab-versus-mycophenolate-mofetil-in-interstitial-lung-disease-secondary-to-connective-tissue-disease/. Accessed January 25, 2020.
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