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      Effect of tumor necrosis factor inhibitors on interstitial lung disease in rheumatoid arthritis: angel or demon?

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          Objectives: This study evaluated the correlation between tumor necrosis factor alpha inhibitor (TNF-I) and interstitial lung disease (ILD) in rheumatoid arthritis (RA). We aimed to raise awareness and consummate therapy by summarizing the characteristics of the adverse events of ILD.

          Methods: A comprehensive search of the PubMed, Embase, Ovid, Cochrane, China National Knowledge Infrastructure, and Wanfang databases was performed from inception to November 2018. Statistical analysis of demographic characteristics, clinical features, and relative risks was performed using Microsoft Excel 2007 and SPSS version 20.0.

          Results: A total of 7 eligible articles and another 28 case reports were enrolled. The 7 cohort studies demonstrated the tendency that ILD cases might not benefit from TNF-I therapy. TNF-I might be associated with ILD adverse events. The case reports further confirmed these findings, as most (87.5%) of the cases showed that TNF-1 was harmful to patients with ILD and even resulted in a 35% mortality rate. Further investigation revealed that ILD adverse events tended to appear in female patients with a long RA history ( p<0.05). The subgroup analysis suggested that early detection and precise treatment are key factors in determining survival or death when an ILD adverse event occurs. A large proportion of ILD adverse events (48.6%) appeared at 2.38±1.03 weeks after the infusion of infliximab.

          Conclusion: A fresh look at the evidence highlights that TNF-I might be associated with ILD adverse events in RA, which can induce more severe pulmonary symptoms and even result in death. Therefore, more attention should be paid to effective prevention, early diagnosis, and precise management. Notably, further prospective cohort studies are warranted to better interpret the association or causality between TNF-I and ILD.

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          Most cited references 46

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          Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years.

          To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence. Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955-94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1-42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews. ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmö, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity. There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA.
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            Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern.

            Interstitial lung disease (ILD) is a frequent extraarticular manifestation of rheumatoid arthritis (RA). While the nonspecific interstitial pneumonia pattern predominates in most forms of connective tissue-associated ILD, studies in patients with RA-associated ILD (RA-ILD) suggest that the usual interstitial pneumonia (UIP) pattern is more common in this patient population. High-resolution CT (HRCT) scans appear accurate in identifying UIP pattern in many patients with RA-ILD. Although the data are limited, UIP pattern appears to predict worse survival in RA-ILD patients. Larger, prospective, multicenter studies are needed to confirm this finding. We propose that the evaluation of patients with RA-ILD should focus on identifying those with UIP pattern on HRCT scans, as these patients are likely to carry a worse prognosis. In patients in whom the underlying pattern cannot be determined by HRCT scanning, surgical lung biopsy should be considered.
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              Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: a systematic literature review.

              To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                01 July 2019
                : 13
                : 2111-2125
                [1 ] Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, People’s Republic of China
                Author notes
                Correspondence: Shenghao TuInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1095, Wuhan430022, People’s Republic of ChinaTel +86 27 8366 3402 Email shtu@ 123456tjh.tjmu.edu.cn
                © 2019 Huang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 2, Tables: 4, References: 51, Pages: 15


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