Otsuji Naotatsu, Sugiyama Kumiya, Owada Takayoshi, Arifuku Hajime, Koyama Kenya, Hirata Hirokuni, Fukushima Yasutsugu
Department of Respiratory Medicine and Clinical Immunology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan.
National Hospital Organization Utsunomiya Hospital, Utsunomiya, Tochigi, Japan.
Open Access Rheumatol. 2024 Jun 11;16:127-135. doi: 10.2147/OARRR.S462662. eCollection 2024.
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.
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.
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 (R = 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.
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.
类风湿关节炎（RA）合并间质性肺疾病（ILD）的预后特别差。尽管在RA治疗中应使用不会促使ILD进展的药物，但目前尚未确立此类药物。本研究评估了托珠单抗在ILD活性方面的安全性。
本研究前瞻性纳入了2014年4月至2022年6月期间在埼玉医科大学国际医疗中心接受托珠单抗治疗的所有55例RA合并ILD患者。分别将基质金属蛋白酶-3（MMP-3）和KL-6作为RA和ILD活性的生物标志物进行结局测量，并分析它们之间的关系。
治疗6个月时，MMP-3和KL-6均显著改善（分别为P < 0.001和P < 0.05），且观察到MMP-3与KL-6之间存在弱相关性（R = 0.086，P = 0.087）。因RA进展导致MMP-3升高的组在6个月时的KL-6显著高于RA病情改善的组（P < 0.05）。此外，计算机断层扫描显示ILD进展的组的MMP-3显著高于ILD改善或无变化的组（分别为P < 0.05和P < 0.01）。6个月时死亡率为0%，1年时为2.0%，2年时为16.7%，3年时为32.4%，且因呼吸道感染导致的ILD急性加重所致死亡率随时间增加。
在治疗6个月时发现RA活性与ILD活性相关。托珠单抗似乎不影响ILD进展机制，因为大多数患者在6个月内使用托珠单抗时MMP-3和KL-6均有改善，而在此期间预计该药物会直接影响肺部。然而，治疗开始1年后呼吸道感染使ILD加重。由于包括托珠单抗在内的免疫抑制药物有呼吸道感染风险，识别感染的早期迹象很重要。
