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Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease.

ABSTRACT: The antifibrotic therapies nintedanib and pirfenidone were first approved by the United States for the treatment of idiopathic pulmonary fibrosis in 2014. In 2020, nintedanib received U.S. Food and Drug Administration (FDA) approval for the treatment of all progressive fibrosing interstitial lung disease (ILD). Given that a major cause of mortality and morbidity in the idiopathic inflammatory myopathies (IIM) is progressive interstitial lung disease and respiratory failure, antifibrotic therapies may be useful as adjuvant to traditional immunosuppression. However, randomized controlled trials of antifibrotic therapies in IIM are lacking. The purpose of this review is to (1) summarize the mechanism of action of nintedanib and pirfenidone in ILD with possible role in IIM-ILD, (2) review the clinical data supporting their use in interstitial lung disease in general, and more specifically in connective tissue disease associated ILD, and (3) discuss the evidence and remaining challenges for using antifibrotic therapies in IIM-ILD.

SUBMITTER: Wilfong EM

PROVIDER: S-EPMC8669869 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease.

Wilfong Erin M EM Aggarwal Rohit R

Therapeutic advances in musculoskeletal disease 20211209

The antifibrotic therapies nintedanib and pirfenidone were first approved by the United States for the treatment of idiopathic pulmonary fibrosis in 2014. In 2020, nintedanib received U.S. Food and Drug Administration (FDA) approval for the treatment of all progressive fibrosing interstitial lung disease (ILD). Given that a major cause of mortality and morbidity in the idiopathic inflammatory myopathies (IIM) is progressive interstitial lung disease and respiratory failure, antifibrotic therapie ...[more]

PMID: 34917177

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Project description:OBJECTIVE:To clarify prognostic factors for idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD). DESIGN:Systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation system. DATA SOURCES:Medline, EMBASE and Science Citation Index Expanded were searched through 9 August 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:The review includes primary studies addressing all-cause mortality of IIM-associated ILD. Potential prognostic factors were any clinical information related to the outcome. DATA EXTRACTION AND SYNTHESIS:Two reviewers extracted relevant data independently and assessed risk of bias using the Quality in Prognostic Studies tool. Meta-analysis was conducted using a random effects model and if inappropriate the results were reported qualitatively. Prognostic factors were determined based on statistically significant results derived from multivariate analysis. RESULTS:Of a total of 5892 articles returned, 32 were deemed eligible for analysis and cumulatively, these studies reported 28 potential prognostic factors for all-cause mortality. Each study was subject to certain methodological constraints. The four prognostic factors, which demonstrated statistically significant results on both univariate and multivariate analyses, were as follows: age (MD 5.90, 3.17-8.63/HR 1.06, 1.02-1.10 and 2.31, 1.06-5.06), acute/subacute interstitial pneumonia (A/SIP) (OR 4.85, 2.81-8.37/HR 4.23, 1.69-12.09 and 5.17, 1.94-13.49), percentage of predicted forced vital capacity (%FVC) (OR 0.96, 0.95-0.98/HR 0.96, 0.93-0.99) and anti-Jo-1 antibody (OR 0.35, 0.18-0.71/HR 0.004, 0.00003-0.54) (univariate/multivariate, 95% CI). Other prognostic factors included ground glass opacity/attenuation (GGO/GGA) and extent of radiological abnormality. The quality of the presented evidence was rated as either low or very low. CONCLUSIONS:Older age, A/SIP, lower value of %FVC, GGO/GGA and extent of radiological abnormality were demonstrated to predict poor prognosis for IIM-associated ILD while a positive test for anti-Jo-1 antibody indicated better prognosis. However, given the weak evidence they should be interpreted with caution. TRIAL REGISTRATION NUMBER:CRD42016036999.

Project description:Objectives: To initially clarify the efficacy and tolerability of nintedanib in patients with idiopathic-inflammatory-myopathy-related interstitial lung disease (IIM-ILD). Methods: A retrospective, real-world analysis was conducted in IIM-ILD patients who regularly received outpatient visit or hospitalization from January 2018 to March 2020 in three centers. And the patients were divided into two groups depending on presence or absence of nintedanib therapy. Comparisons, Kaplan-Meier survival analysis and propensity score matching were made to identify difference in time to death from any cause, incidence of rapidly progressive interstitial lung disease (RP-ILD) and comorbidity of pulmonary infection between the two groups. The following logistic regression analyses and Cox proportional-hazard regression analyses were used to verify the therapeutic value of nintedanib as well as clinical significance of other factors. Adverse events were descriptively recorded. Results: Thirty-six patients receiving nintedanib therapy and 115 patients without use of nintedanib were included. Before and after propensity score matching, the primary comparisons revealed better survival (P = 0.015, P = 0016, respectively) and lower incidence of RP-ILD (P = 0.017, P = 0.014, respectively) in patients with nintedanib therapy. Logistic regression analysis identified that disease activity (P < 0.001), percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.036), nintedanib therapy (P = 0.004, OR value = 0.072) and amyopathic dermatomyositis (ADM, P = 0.012) were significantly correlated with RP-ILD. Cox proportional hazards regression analysis suggested that disease activity (P < 0.001), anti-MDA5 antibody (P < 0.001) and nintedanib therapy (P = 0.013, HR value=0.268) were significantly associated with survival of IIM-ILD patients. Similar results can also be seen in analyses after propensity score matching. In the 36 patients with nintedanib therapy, diarrhea was the most common adverse event (44.4%) and hepatic insufficiency contributed to most dosage reduction (44.4% of nine patients) or therapy discontinuation (60.0% of five patients). Conclusions: Nintedanib was found to reduce incidence of RP-ILD and improve survival in IIM-ILD patients in a real-world setting. Anti-MDA5 antibody could be taken as a risk factor for unfavorable outcome. ADM was significantly correlated with occurrence of RP-ILD. In addition to the most frequent diarrhea, hepatic insufficiency was closely related to dosage reduction or therapy discontinuation.

Project description:The lung is a common site of complications of systemic connective tissue disease (CTD), and lung involvement can present in several ways. Interstitial lung disease (ILD) and pulmonary hypertension are the most common lung manifestations in CTD. Although it is generally thought that interstitial lung disease develops later on in CTD it is often the initial presentation ("lung dominant" CTD). ILD can be present in most types of CTD, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease. Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis. Pulmonary hypertension (PH) can present as a primary vasculopathy in pulmonary arterial hypertension or in association with ILD (PH-ILD). Therefore, detailed history, physical examination, targeted serologic testing, and, occasionally, lung biopsy are needed to diagnose CTD-ILD, whereas both non-invasive and invasive assessments of pulmonary hemodynamics are needed to diagnose pulmonary hypertension. Immunosuppression is the mainstay of treatment for ILD, although data from randomized controlled trials (RCTs) to support specific treatments are lacking. Furthermore, treatment strategies vary according to the clinical situation-for example, the treatment of a patient newly diagnosed as having CTD-ILD differs from that of someone with an acute exacerbation of the disease. Immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to CTD; more commonly, selective pulmonary vasodilators are used. For both diseases, comorbidities such as sleep disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated. Lung transplantation should be considered in patients with advanced disease but is not always feasible because of other manifestations of CTD and comorbidities. Clinical trials of novel therapies including immunosuppressive therapies are needed to inform best treatment strategies.

Dataset Information

Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease.

Publications

Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease.

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