Tocilizumab offers hope for rheumatoid arthritis with interstitial lung disease, but caution advised against respiratory infections

A new study conducted at Dokkyo Medical University Saitama Medical Center has provided promising insights into the safety and efficacy of tocilizumab for patients suffering from rheumatoid arthritis (RA) complicated by interstitial lung disease (ILD). The prognosis for these patients is typically poor, and finding a treatment that does not exacerbate ILD has been a significant challenge. The study found a connection between RA and ILD activity after six months of tocilizumab treatment. While the drug did not appear to speed up ILD progression, there was an increase in respiratory infections and ILD exacerbations after one year, highlighting the need for careful long-term management due to the drug’s potential to suppress the immune system. Early detection and management of infections are critical for improving long-term outcomes for patients on tocilizumab. 

Published in Open Access Rheumatology, the prospective study spanned from April 2014 to June 2022 and enrolled 55 patients diagnosed with both RA and ILD. At the six-month mark, significant improvements were observed in both MMP-3 and KL-6 levels, suggesting that tocilizumab had a beneficial effect on both RA and ILD within this period. A weak correlation was identified between matrix metalloproteinase-3 (MMP-3) and Krebs von den Lungen-6 (KL-6) levels. Patients whose RA worsened, indicated by increased MMP-3, also exhibited higher KL-6 levels, illustrating a parallel progression of ILD. Those with ILD progression evident on computed tomography scans had significantly higher MMP-3 levels compared to patients whose ILD improved or remained unchanged. Mortality rates were 0% at six months, 2.0% at one year, 16.7% at two years, and 32.4% at three years, with mortality from acute exacerbation of ILD due to respiratory infections increasing over time. 

Tocilizumab is a humanized antibody targeting the IL-6 receptor, binding to both soluble and membrane-bound forms of the receptor. In blood, tocilizumab effectively inhibits IL-6 signaling by almost completely blocking transmembrane signaling. It hinders IL-6-induced biological activities in cells expressing both membrane-bound IL-6R and gp130 molecules, as well as in cells with gp130 alone where IL-6/IL-6R complex formation occurs. Additionally, tocilizumab can dissociate pre-formed IL-6/IL-6R complexes, making it highly effective in blocking IL-6 signal transduction pathways. 

A study by Manfredi et al. reported that tocilizumab demonstrated a good safety profile and potential to stabilize lung involvement in RA-ILD. The national multicenter study analyzed the effects of tocilizumab on 28 patients with RA-ILD. Over a 30-month follow-up, forced vital capacity and diffusing capacity of the lung for carbon monoxide remained stable or improved in most patients, with high-resolution computed tomography scans showing stability in the majority., addressing a critical unmet need in managing this severe RA manifestation. Another study by Otsuji et al. that tocilizumab significantly improved RA activity without progressing ILD, suggesting it can be safely administered to patients with both conditions. The study evaluated the safety of tocilizumab in 34 patients with rheumatoid arthritis and interstitial lung disease. Levels of MMP-3 significantly decreased from 380 ± 370 ng/mL before treatment to 214 ± 216 ng/mL at 2 months and 208 ± 245 ng/mL at 6 months. KL-6 levels also showed improvement. Chest CT scans of 22 patients showed no progression of ILD one year after treatment. 

This study underscores the potential of tocilizumab as a viable treatment for RA patients with ILD, offering a ray of hope for improved management of these complex cases. However, the findings also highlight the need for vigilant monitoring for respiratory infections. Further research is required to establish comprehensive guidelines for the long-term management of these patients to mitigate infection risks while harnessing the benefits of tocilizumab. 


  1. Otsuji N, Sugiyama K, Owada T, Arifuku H, Koyama K, Hirata H, et al. Safety of Tocilizumab on Rheumatoid Arthritis in Patients with Interstitial Lung Disease. Open Access Rheumatol. 2024;16:127–35. 
  1. Manfredi A, Cassone G, Furini F, Gremese E, Venerito V, Atzeni F, et al. Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicentre retrospective study. Intern Med J. 2020 Sep;50(9):1085–90. 
  1. Otsuji N, Sugiyama K, Arifuku H, Nakano K, Watanabe H, Wakayama T, et al. Effect of tocilizumab on interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Eur Respir J. 2020 Sep; 56: 747. 
  1. Okuda Y. Review of tocilizumab in the treatment of rheumatoid arthritis. Biologics. 2008 Mar;2(1):75-82.