Safety of Tocilizumab on Rheumatoid Arthritis in Patients with Interstitial Lung Disease

Abstract

Naotatsu Otsuji,1 Kumiya Sugiyama,1,2 Takayoshi Owada,1 Hajime Arifuku,1 Kenya Koyama,1 Hirokuni Hirata,1 Yasutsugu Fukushima1 1Department of Respiratory Medicine and Clinical Immunology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan; 2National Hospital Organization Utsunomiya Hospital, Utsunomiya, Tochigi, JapanCorrespondence: Kumiya Sugiyama, National Hospital Organization Utsunomiya Hospital, 2160, Shimo-Okamoto, Utsunomiya, Tochigi, 329-1193, Japan, Email [email protected]: The prognosis of rheumatoid arthritis (RA) with interstitial lung disease (ILD) is particularly poor. Although drugs that do not contribute to the progression of ILD should be used in RA treatment, none have been established. This study evaluated the safety of tocilizumab in terms of ILD activity.Patients and Methods: This study prospectively enrolled all 55 patients with RA complicated by ILD who were treated with tocilizumab at Dokkyo Medical University Saitama Medical Center from April 2014 to June 2022. The outcome measures were MMP-3 and KL-6 as biomarkers of RA and ILD activity, respectively, and the relationship between them was analyzed.Results: Both MMP-3 and KL-6 were significantly improved at 6 months of treatment (P < 0.001 and P < 0.05, respectively), and a weak correlation between MMP-3 and KL-6 was observed (R2 = 0.086, P = 0.087). The group with increased MMP-3 due to RA progression had significantly higher KL-6 at 6 months compared with the group with RA improvement (P < 0.05). Also, the group with ILD progression on computed tomography had significantly higher MMP-3 compared with the groups with improvement or no change of ILD (P < 0.05 and P < 0.01, respectively). The mortality rate was 0% at 6 months, 2.0% at 1 year, 16.7% at 2 years, and 32.4% at 3 years, and mortality from acute exacerbation of ILD due to respiratory infection increased over time.Conclusion: RA activity and ILD activity were found to be related at 6 months of treatment. Tocilizumab does not seem to affect the mechanism of ILD progression, as most patients showed improvement in both MMP-3 and KL-6 with tocilizumab within 6 months, when this drug would be expected to affect the lungs directly. However, respiratory infection exacerbated ILD from 1 year after the start of treatment. As immunosuppressive drugs, including tocilizumab, have a risk of respiratory infection, it is important to identify early signs of infection.Keywords: interstitial lung disease, Krebs von den Lungen-6, KL-6, matrix metalloproteinase-3, MMP-3, rheumatoid arthritis, mortality, tocilizumab

Keywords

• interstitial lung disease
• krebs von den lungen-6
• kl-6
• matrix metalloproteinase-3
• mmp-3
• rheumatoid arthritis
• mortality
• tocilizumab