title: Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Biological therapy represents important advances in alleviating rheumatoid arthritis (RA), but the effect on interstitial lung disease (ILD) has been controversial. The objective of this study was to assess the risk of such treatment for patients with ILD.
  
  
  METHODS
  Case-control cohorts.
  
  
  METHODS
  Single centre in Japan.
  
  
  METHODS
  This study included 163 patients with RA who underwent biological therapy.
  
  
  METHODS
  We assessed chest CT before initiation of biological therapy and grouped 163 patients according to the presence of ILD (with (n=58) and without pre-existing ILD (n=105)). Next, we evaluated serial changes of chest CT after treatment and visually assessed the emergence of ILD or its progression, which was referred to as an 'ILD event'. Then, we also classified the patients according to the presence of ILD events and analysed their characteristics.
  
  
  RESULTS
  Tumour necrosis factor (TNF) inhibitors were administered to more patients with ILD events than those without ILD events (88% vs 60%, p<0.05), but recipients of tocilizumab or abatacept did not differ in this respect. Of 58 patients with pre-existing ILD, 14 had ILD events, and that proportion was greater than for those without pre-existing ILD (24% vs 3%, p<0.001). Of these 14 patients, all were treated with TNF inhibitors. Four patients developed generalised lung disease and two died from ILD progression. Baseline levels of KL-6 were similar in both groups, but increased in patients with ILD events.
  
  
  CONCLUSIONS
  TNF inhibitors have the potential risk of ILD events, particularly for patients with pre-existing ILD, and KL-6 is a valuable surrogate marker for detecting ILD events. Our data suggest that non-TNF inhibitors are a better treatment option for these patients.
authors.affiliation: Department of Rheumatology, Kameda Medical Center, Kamogawa City, Chiba, Japan.
authors.forename: Tamao
authors.initials: T
authors.lastname: Nakashita
authors.affiliation: Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Respiratory Internal Medicine, Kameda Medical Center, Kamogawa City, Chiba, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kaneko
authors.affiliation: Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Rheumatology, Kameda Medical Center, Kamogawa City, Chiba, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Motojima
mesh_terms: D000069594:Abatacept; D000068879:Adalimumab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D016022:Case-Control Studies; D018450:Disease Progression; D000068800:Etanercept; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects; D007074:Immunoglobulin G / Q000009:adverse effects; D000069285:Infliximab; D008168:Lung / Q000000981:diagnostic imaging*; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D018796:Immunoconjugates; D007074:Immunoglobulin G; C060192:MUC1 protein, human; D018396:Mucin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept; D000069285:Infliximab; D000068879:Adalimumab; C502936:tocilizumab; D000068800:Etanercept
keywords: Rheumatoid arthritis; Tumor necrosis factor inhibitors