title: Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control study.
abstract: The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60 years or older (OR 4.5, 95 % CI 2.2-9.4, P < 0.0001), smoking habit (OR 2.9, 95 % CI 1.5-5.5, P = 0.002), and high rheumatoid factor levels (OR 2.8, 95 % CI 1.4-5.5, P = 0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48 weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24 weeks (20.8 vs. 6.2, P = 0.019). Univariate analysis showed that CDAI > 10 at 24 weeks was a risk factor for acute exacerbation (OR 4.7, 95 % CI 2.1-10.4, P = 0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Akiyama
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tsutake@z5.keio.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016015:Logistic Models; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D060735:Pharmacovigilance; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
keywords: Acute exacerbation; Disease activity; Interstitial lung disease; Rheumatoid arthritis; Tocilizumab