Eternacept for the treatment of patients with rheumatoid arthritis and concurrent interstitial lung disease.

Tumour necrosis factor-α (TNF-α)-blocking agents are increasingly used in the management of refractory rheumatoid arthritis (RA). Although effective, they are associated with rare but potentially fatal adverse effects, including interstitial lung disease (ILD). In patients with pre-existing ILD, eternacept (ETN) monotherapy is often regarded as a suitable choice. Other anti-TNF-α blockers such as infliximab and adalimumab, are used in combination therapy with methotrexate (MTX) in most of the cases. We report on a case of fatal exacerbation of ILD in a patient given ETN monotherapy and review the literature on ETN-associated ILD. We report on a case of a 75-year-old male with RA who developed severe ILD after the introduction of ETN, and we undertook a literature search to identify other reports of similar cases. We then critically assessed those reports. In addition to our case, 11 other patients have been reported to have developed ILD in association with the use of ETN. Six patients had pre-existing ILD. Although four patients received MTX, eight patients developed severe ILD without MTX. Ten patients recovered after termination of ETN, although two patients died. Although ETN is often regarded as safe for patients with ILD, our case and the literature reports suggest that caution is still required.

Horai Y ，Miyamura T ，Shimada K ，Takahama S ，Minami R ，Yamamoto M ，Suematsu E ... -  《-》

The safety and efficacy of adding etanercept to methotrexate or methotrexate to etanercept in moderately active rheumatoid arthritis patients previously treated with monotherapy.

van der Heijde D ，Burmester G ，Melo-Gomes J ，Codreanu C ，Mola EM ，Pedersen R ，Freundlich B ，Chang DJ ，Etanercept Study 400 Investigators ... -  《-》

Interstitial lung disease induced or exacerbated by TNF-targeted therapies: analysis of 122 cases.

To analyze the clinical characteristics, outcomes, and patterns of association with the different biologic agents used in all reported cases of adult patients developing interstitial lung disease (ILD) after biologic therapy. In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project. One objective was to collect data on autoimmune diseases secondary to the use of biologic agents by quarterly Medline search surveillance of reported cases. For this study, the baseline included articles published between January 1990 and March 2010, including the MeSH term "lung diseases, interstitial" as the key research term. In addition, we report an unpublished case of ILD secondary to biologic therapy. There are 122 reported cases of new-onset or exacerbation of ILD secondary to administration of biologic therapies. Biologic agents associated with ILD were overwhelmingly anti-tumor necrosis factor agents (etanercept in 58 cases and infliximab in 56) and were administered for rheumatoid arthritis in 108 (89%) patients. ILD appeared a mean of 26 weeks after initiation of biologic agents. ILD was confirmed by pulmonary biopsy in 26 cases, although a specific histopathologic description was detailed in only 20: 7 patients were classified as usual interstitial pneumonia, 6 as nonspecific interstitial pneumonia, 5 as organizing pneumonia, 1 as diffuse alveolar damage, and 1 as lymphoid interstitial pneumonia. Treatment of ILD included withdrawal of biologic agents in all cases but 1. The outcome of ILD was detailed in 52 cases. Complete resolution was reported in 21 (40%) cases, improvement or partial resolution in 13 (25%), and no resolution in 18 (35%). Fifteen (29%) patients died during the follow-up, the majority (70%) during the first 5 weeks after initiating biologic therapy. In comparison with survivors, patients who died were aged >65 years (67% vs 33%, P = 0.036), with later onset of ILD (46 weeks vs 15 weeks, P = 0.006), received immunosuppressive drugs more frequently (33% vs 8%, P = 0.036), and more often had a previous diagnosis of ILD (67% vs 29%, P = 0.025). We found that 97% of cases of ILD associated with biologic agents were associated with agents blocking tumor necrosis factor-α, a cytokine that has been implicated in the pathophysiology of pulmonary fibrosis. Strikingly, drug-induced ILD had a poor prognosis, with an overall mortality rate of around one third, rising to two thirds in patients with preexisting ILD.

Perez-Alvarez R ，Perez-de-Lis M ，Diaz-Lagares C ，Pego-Reigosa JM ，Retamozo S ，Bove A ，Brito-Zeron P ，Bosch X ，Ramos-Casals M ... -  《-》

Acute exacerbation of preexisting interstitial lung disease after administration of etanercept for rheumatoid arthritis.

Hagiwara K ，Sato T ，Takagi-Kobayashi S ，Hasegawa S ，Shigihara N ，Akiyama O ... -  《JOURNAL OF RHEUMATOLOGY》

Patient-reported health outcomes in a trial of etanercept monotherapy versus combination therapy with etanercept and methotrexate for rheumatoid arthritis: the ADORE trial.

van Riel PL ，Freundlich B ，MacPeek D ，Pedersen R ，Foehl JR ，Singh A ，ADORE Study Investigators ... -  《-》