Mycophenolate Mofetil Improves Lung Function in Connective Tissue Disease-associated Interstitial Lung Disease

Objective.Small series suggest mycophenolate mofetil (MMF) is well tolerated and may be an effective therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). We examined the tolerability and longitudinal changes in pulmonary physiology in a large and diverse cohort of patients with CTD-ILD treated with MMF.Methods.We identified consecutive patients evaluated at our center between January 2008 and January 2011 and prescribed MMF for CTD-ILD. We assessed safety and tolerability of MMF and used longitudinal data analyses to examine changes in pulmonary physiology over time, before and after initiation of MMF.Results.We identified 125 subjects treated with MMF for a median 897 days. MMF was discontinued in 13 subjects. MMF was associated with significant improvements in estimated percentage of predicted forced vital capacity (FVC%) from MMF initiation to 52, 104, and 156 weeks (4.9% ± 1.9%, p = 0.01; 6.1% ± 1.8%, p = 0.0008; and 7.3% ± 2.6%, p = 0.004, respectively); and in estimated percentage predicted diffusing capacity (DLCO%) from MMF initiation to 52 and 104 weeks (6.3% ± 2.8%, p = 0.02; 7.1% ± 2.8%, p = 0.01). In the subgroup without usual interstitial pneumonia (UIP)-pattern injury, MMF significantly improved FVC% and DLCO%, and in the subgroup with UIP-pattern injury, MMF was associated with stability in FVC% and DLCO%.Conclusion.In a large diverse cohort of CTD-ILD, MMF was well tolerated and had a low rate of discontinuation. Treatment with MMF was associated with either stable or improved pulmonary physiology over a median 2.5 years of followup. MMF appears to be a promising therapy for the spectrum of CTD-ILD.

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Faculty Opinions recommendation of Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.31377.487868 ◽

2006 ◽

Author(s):

Charlie Strange

Keyword(s):

Mycophenolate Mofetil ◽

Interstitial Lung Disease ◽

Lung Function ◽

Connective Tissue ◽

Lung Disease ◽

Connective Tissue Disease

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Effect of Cotreatment with Corticosteroids in Connective Tissue Related Lung Disease (CTD-ILD) Patients on Mycophenolate Mofetil (MMF)

10.21203/rs.3.rs-208857/v1 ◽

2021 ◽

Author(s):

Roberto Caricchio ◽

Erin R Narewski ◽

Ryan Townsend ◽

Stephen Codella ◽

Jin Sun Kim ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Connective Tissue ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Connective Tissue Disease ◽

Pulmonary Function Tests ◽

Usual Interstitial Pneumonia ◽

University Hospital ◽

Inflammatory Myositis ◽

Idiopathic Inflammatory Myositis

Abstract Introduction: Connective Tissue Disease Related Interstitial Lung Disease (CTD-ILD) is often treated with immunosuppressant medications; common among these is Mycophenolate Mofetil (MMF). We hypothesized that co-treatment with corticosteroids would impact disease progression.Methods: We examined a consecutive cohort of CTD-ILD patients followed at Temple University Hospital in Philadelphia, PA since 2015 who had pulmonary function tests (PFTs) performed by American Thoracic Society (ATS)/European Respiratory Society (ERS) Criteria at least one year apart. All patients were treated for CTD-ILD with MMF used either as sole therapy or as combination therapy with prednisone. Univariate logistic analyses were performed revealing the odds ratio (OR) for improvement or worsening of several PFT values (including forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), and six-minute walk (6MW)) greater than the minimal clinically important difference (MCID) for each value.Results: We included 103 patients (74 women) with an average age of 60 ± 11 years, 49% of our cohort were current or former smokers, and mean BMI was 29 ± 7 kg/m2. Patients were observed on treatment for an average of 23 months. CTD distribution included 25% mixed connective tissue disease (MCTD), 24% systemic sclerosis (SSc), 17% rheumatoid arthritis (RA), 14% systemic lupus erythematosus (SLE), 10% other idiopathic inflammatory myositis (IIM) syndromes, 7% Antisynthetase Syndrome, 5% Sjӧgren’s syndrome. Non-specific interstitial pneumonia (NSIP) was the majority (45%) ILD pattern noted, Usual Interstitial Pneumonia (UIP) 35%, and other types were less prevalent (20%). The majority of patients received corticosteroids as co-treatment with MMF (75 patients (72%)) with a mean daily dose of 15 ± 16 mg of prednisone. Mean daily MMF dose was 1144 ± 675 mg. Glucocorticoid treatment was not associated with significant improvements in PFT values, including FVC, DLCO, and 6MW distance walked.Conclusion: In this small cohort, patients with CTD-ILD receiving MMF did not demonstrate improved lung function when receiving co-treatment with corticosteroids, but larger prospective studies are needed to better elucidate the effect of corticosteroids on this vulnerable group of patients.

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Mycophenolate mofetil (MMF) for the treatment of connective tissue disease-associated interstitial lung disease (ILD)

10.1002/14651858.cd009911 ◽

2012 ◽

Author(s):

Natalie E Stolagiewicz ◽

Adrian Draper ◽

Lucy EE Schomberg ◽

Felix Chua

Keyword(s):

Mycophenolate Mofetil ◽

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Connective Tissue Disease

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Centrilobular Fibrosis in Fibrotic (Chronic) Hypersensitivity Pneumonitis, Usual Interstitial Pneumonia, and Connective Tissue Disease–Associated Interstitial Lung Disease

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2019-0628-ra ◽

2020 ◽

Vol 144 (12) ◽

pp. 1509-1516

Author(s):

Andrew Churg

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Connective Tissue Disease ◽

Hypersensitivity Pneumonitis ◽

Interstitial Fibrosis ◽

Usual Interstitial Pneumonia ◽

Diffuse Fibrosis ◽

Chronic Hypersensitivity Pneumonitis

Context.— Various pulmonary diseases can produce centrilobular (peribronchiolar) fibrosis, which may be isolated or associated with other patterns of more diffuse fibrosis. The major forms of interstitial lung disease in which centrilobular fibrosis is found are fibrotic (chronic) hypersensitivity pneumonitis, connective tissue disease–associated interstitial lung disease, and (a disputed issue) usual interstitial pneumonia/idiopathic interstitial fibrosis. Objective.— To review recent literature that addresses separation of these entities. Data Sources.— Data comprised recent publications. Conclusions.— In a specially constructed multidisciplinary discussion exercise, it was found that peribronchiolar metaplasia affecting more than half the bronchioles or more than 2 foci of peribronchiolar metaplasia per square centimeter of biopsy area was strongly associated with a confident diagnosis of fibrotic hypersensitivity pneumonitis. Giant cells or granulomas were only found in cases with a greater than 50% diagnostic confidence in hypersensitivity pneumonitis. Conversely, greater numbers of fibroblast foci per square centimeter and increasing measured amounts of subpleural fibrosis favored a diagnosis of usual interstitial pneumonia. Recent data also suggest that centrilobular fibrosis can be found in usual interstitial pneumonia, although the presence of centrilobular fibrosis statistically favors an alternate diagnosis. Connective tissue disease is a major confounder because many patterns are very similar to fibrotic hypersensitivity pneumonitis or usual interstitial pneumonia. Genetic abnormalities, such as the MUC5B minor allele overlap, in these conditions and at this point cannot be used for discrimination. Thus, the separation of fibrotic hypersensitivity pneumonitis and usual interstitial pneumonia remains a difficult problem. Accurate biopsy diagnosis of all of these diseases requires correlation with imaging and clinical findings, and is crucial for treatment.

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Prognostic Value of Human Epididymis Protein 4 in Connective Tissue Disease-Associated Interstitial Lung Disease with a Usual Interstitial Pneumonia Phenotype

SSRN Electronic Journal ◽

10.2139/ssrn.4000362 ◽

2022 ◽

Author(s):

Kaifang Meng ◽

Mi Tian ◽

Xianhua Gui ◽

Miaomiao Xie ◽

Yujuan Gao ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Connective Tissue Disease ◽

Prognostic Value ◽

Usual Interstitial Pneumonia ◽

Human Epididymis Protein 4 ◽

Human Epididymis

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Morphologic Aspects of Interstitial Pneumonia With Autoimmune Features

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0528-ra ◽

2018 ◽

Vol 142 (9) ◽

pp. 1080-1089 ◽

Cited By ~ 3

Author(s):

Ellen Caroline Toledo do Nascimento ◽

Bruno Guedes Baldi ◽

Marcio Valente Yamada Sawamura ◽

Marisa Dolhnikoff

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Connective Tissue Disease ◽

Usual Interstitial Pneumonia ◽

Connective Tissue Diseases ◽

Distinct Subgroup ◽

Management Protocol ◽

The Impact

Context.— Interstitial lung disease, a common complication observed in several connective tissue diseases, causes significant morbidity and mortality. Similar to individuals with connective tissue diseases, a significant subgroup of patients with clinical and serologic characteristics suggestive of autoimmunity but without confirmed specific connective tissue disease presents with associated interstitial lung disease. These patients have been classified using different controversial nomenclatures, such as undifferentiated connective tissue disease–associated interstitial lung disease, lung-dominant connective tissue disease, and autoimmune featured interstitial lung disease. The need for a better understanding and standardization of this entity, interstitial lung disease with autoimmune features, and the need for an adequate management protocol for patients resulted in the introduction of a new terminology in 2015: interstitial pneumonia with autoimmune features. This new classification requires a better comprehension of its diagnostic impact and the influence of its morphologic aspects on the prognosis of patients. Objective.— To review the diagnostic criteria for interstitial pneumonia with autoimmune features, with an emphasis on morphologic aspects. Data Sources.— The review is based on the available literature, and on pathologic, radiologic, and clinical experience. Conclusions.— The interstitial pneumonia with autoimmune features classification seems to identify a distinct subgroup of patients with different prognoses. Studies show that nonspecific interstitial pneumonia and usual interstitial pneumonia are the most prevalent morphologic patterns and show discrepant results on the impact of the usual interstitial pneumonia pattern on survival. Prospective investigations are necessary to better define this subgroup and to determine the prognosis and appropriate clinical management of these patients.

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