Background Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is a common extra-articular manifestation and acute exacerbation (AE) is sometimes critical. While the prognosis of RA has been improved with biologic agents including tocilizumab (TCZ), risk factors associated with AE during biologic treatment remain unclear.
Objectives To investigate risk factors associated with AE in patients with RA-ILD during TCZ treatment.
Methods Three hundred ninety five RA patients treated with TCZ in our institution from June 2008 to December 2014 were retrospectively reviewed. Patients were grouped based on existence (RA-ILD) or absence (non-ILD) of ILD according to high-resolution computed tomography (HRCT). AE of RA-ILD was defined based on the IPF Clinical Research Network criteria1 with a modification for adaptation to RA-ILD: previous diagnosis of RA-ILD, HRCT with new bilateral ground-glass opacities with or without areas of consolidation superimposed on RA-ILD, and the absence of infection or another identifiable etiology. RA-ILD group was further subgrouped into with or without AE (AE and non-AE group, respectively). Characteristics at baseline and post-treatment were compared.
Results Three hundred seventeen patients were classified into non-ILD and 78 patients (19.7%) were classified into RA-ILD group. Multivariate analysis revealed that risk factors for RA-ILD were age over 60 (OR 11.3; 95% CI 3.9-32.6; p<0.0001), smoking (OR 3.1; 95% CI 1.6-6.1; p=0.001), and positivity of RF (OR 7.8; 95%CI 1.8-34.2; p=0.006). While there was no newly diagnosed RA-ILD in non-ILD group, 6 patients developed AE during TCZ treatment in the RA-ILD group. The incidence of AE in RA-ILD was 3.04 per 100 patient-year and the median duration between the commencement of TCZ and the AE occurrence was 18 (range 11 to 33) months. None of the patients with AE was treated with concomitant methotrexate at the time of AE. Although the baseline characteristics including age, disease duration and RA disease activity were not statistically different between AE and non-AE, patients in non-AE had significantly lower DAS28 and CDAI at 12 weeks after TCZ initiation (DAS28, 2.4 vs 4.5, P<0.0001; CDAI, 6.8 vs 18.1, P<0.0001). In addition, larger number of patients achieved remission or low disease activity with DAS28 and CDAI compared to AE (88.9% vs 0% in DAS28, P<0.0001and 83.3% vs 16.7% in CDAI, P<0.0001).
Conclusions Remaining in high or moderate disease activity at 12 weeks after TCZ initiation associated with AE of RA-ILD. This suggests post-treatment monitoring of disease activity is important not only in aspect of RA itself but also RA-ILD.
Collard HR, Moore BB, Flaherty KR, et al. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176:636-43.
Disclosure of Interest M. Akiyama: None declared, Y. Kaneko Consultant for: Abbvie, Paid instructor for: Eisai Pharmaceutical, Chugai Pharmaceutical, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Speakers bureau: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Janssen, UCB, H. Kondo: None declared, K. Yamaoka Speakers bureau: Pfizer, Chugai Pharma, Mitsubishi-Tanabe Pharma, Takeda Industrial Pharma, GlaxoSmithKline, Nippon Shinyaku, Eli Lilly, Janssen Pharma, Eisai Pharma, Astellas Pharma and Actelion Pharmaceuticals, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd.,SymBio Pharmaceuticals Ltd., Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Paid instructor for: Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., Abbivie GK., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co.,Ltd., Celtrion, Nipponkayaku Co.Ltd