Risk of interstitial lung disease associated with leflunomide treatment in Korean patients with rheumatoid arthritis

Ju, Ji Hyeon; Kim, Sung-Il; Lee, Junhee; S, Lee; Yoo, Wan‐Hee; Choe, Jung‐Yoon; Chung, Seung-Hie; Lee, Sang Hoon; Lee, You-Hyun; Lee, Shin-Seok; Yoon, Hyun‐Jung; Yoon, Chong‐Hyeon; Kim, Ho-Youn; Park, Sung-Hwan

doi:10.1002/art.22666

Cited by 56 publications

(13 citation statements)

References 9 publications

(7 reference statements)

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“…Sathi N et al designed the largest ongoing prospective study and the results suggest that methotrexate pneumonitis does not occur as often as previously thought with an incidence of one case every 192 patient years [39]. Furthermore, ILD is reported in 1% of those taking leflunomide and 0.6% of patients receiving etanercept [40, 41]. The possible link between leflunomide and ILD has evoked increasing concern.…”

Section: Risk Factors For Dildmentioning

confidence: 99%

Drug Induced Interstitial Lung Disease

Schwaiblmair¹

2012

TORMJ

264

209

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With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease.

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Section: Risk Factors For Dildmentioning

confidence: 99%

Drug Induced Interstitial Lung Disease

Schwaiblmair¹

2012

TORMJ

264

209

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“…Leflunomide is also associated with ILD [76], with an increased risk in the setting of preexisting lung disease and a potential relevant impact on survival [77, 78]. Similarly to MTX, hypersensitivity reactions may represent the main mechanism of LEF-induced pneumonitis [79].…”

Section: Dmards and Biological Agents Related Ildmentioning

confidence: 99%

The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

Cavagna

Monti

Grosso

et al. 2013

BioMed Research International

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Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.

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“…In our study, we found that the cumulative dose of leflunomide correlated closely with LSM values, and could be used as an independent predictor for abnormal LSM values. We selected 53 patients (51%) who received both leflunomide and MTX, and obtained the cutoff for the leflunomide cumulative dose of 19,170 mg (5.3 years with 10 mg tablets or 2.6 years with 20 mg tablets), because in Korea, leflunomide is usually administered with MTX [25]. Patients with a cumulative dose of leflunomide over 19,170 mg had a significantly higher risk of having an abnormal LSM value than those with less than 19,170 mg; the hazard ratio was 12.75.…”

Section: Discussionmentioning

confidence: 99%

Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate

et al. 2012

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IntroductionWe identified silent liver fibrosis in patients with rheumatoid arthritis (RA) using transient elastography, and investigated medication that correlated with abnormal liver stiffness measurement (LSM) values.MethodsWe consecutively enrolled 105 patients with RA taking methotrexate over 24 weeks with normal liver functions and no history of underlying chronic liver disease. Blood tests were performed, and body mass index and metabolic syndrome were assessed. We checked LSM values, and adopted 5.3 kPa as the cutoff for abnormal LSM values. The cumulative doses of medications including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, prednisolone, meloxicam, and celecoxib were calculated.ResultsThe median age of patients (20 men and 85 women) was 52.4 years. The median LSM value was 4.7 kPa and 24 (22.9%) patients had abnormal LSM values. Gamma-glutamyltranspeptidase levels and the cumulative doses of leflunomide and prednisolone significantly correlated with LSM values (P<0.05). The cumulative dose of leflunomide, but not methotrexate, was significantly higher in patients with abnormal LSM values than that in patients with normal LSM values (P = 0.008). When RA patients receiving leflunomide plus methotrexate were classified into two groups according to the optimal cutoff cumulative dose of leflunomide (19,170 mg), abnormal LSM values were more frequently identified in patients with high cumulative dose of leflunomide (odds ratio, 12.750; P<0.001).ConclusionsThe cumulative dose of leflunomide was the only independent predictor of abnormal LSM values in patients with RA who had received methotrexate for more than six months.

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Risk of interstitial lung disease associated with leflunomide treatment in Korean patients with rheumatoid arthritis

Cited by 56 publications

References 9 publications

Drug Induced Interstitial Lung Disease

Drug Induced Interstitial Lung Disease

The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate

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