L. Fan, MMed, W. Lyu, MMed, H. Liu, MMed, H. Jiang, MMed, L. Chen, MMed, Y. Liu, MMed, Y. Zhuang, PhD, M. Huang, MMed, M. Cao, MMed, H. Cai, MMed, Y. Xiao, MMed, and J. Dai, PhD, Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu, China.
J Rheumatol. 2022 Dec;49(12):1356-1364. doi: 10.3899/jrheum.220367. Epub 2022 Aug 15.
The efficacy of tofacitinib (TOF) in the early diagnosis of melanoma differentiation-associated gene 5 (MDA5)-related interstitial lung disease (ILD) has been described. However, whether TOF exposure is associated with a reduced 1-year mortality rate remains undetermined.
Patients diagnosed with MDA5-ILD receiving TOF or tacrolimus (TAC) treatment were included. A Cox proportional hazards model, which was adjusted for age, sex, smoking history, anti-MDA5 antibody titers, and concurrent use of other steroid-sparing agents, was performed to compare all-cause mortality and to investigate the risk factors predicting 1-year mortality rates in the 2 treatment groups.
During the study period, 26 patients were treated with TOF and 35 were treated with TAC. The 6-month (38.5% vs 62.9%; = 0.03) and 1-year (44.0% vs 65.7%; = 0.03) mortality rates in the TOF group were significantly lower than those in the TAC group. There were 13 patients diagnosed with rapidly progressive ILD (RP-ILD) in the TOF group and 22 in the TAC group. The majority of deaths occurred in patients with RP-ILD. The 6-month (76.9% vs 95.5%; = 0.02) and 1-year (84.6% vs 100.0%; = 0.02) mortality rates of patients with RP-ILD in the TOF group were also lower than those in the TAC group, respectively. The adjusted model showed that TOF exposure was associated with a lower risk for 1-year mortality (hazard ratio 0.44, 95% CI 0.20-0.96; = 0.04). However, the incidence of adverse events (73.1% vs 74.3%; > 0.99) and medication discontinuation rates (23.1% vs 14.3%; = 0.50) in the TOF and TAC groups were similar, respectively.
Our observational study showed that TOF use might have a potential effect on improving the outcomes of MDA5-ILD. Future clinical trials are needed to assess the long-term efficacy and tolerability of TOF.
已描述托法替布（TOF）在早期诊断黑色素瘤分化相关基因 5（MDA5）相关间质性肺病（ILD）中的疗效。然而，TOF 暴露是否与降低 1 年死亡率相关仍不确定。
纳入接受 TOF 或他克莫司（TAC）治疗的 MDA5-ILD 患者。采用 Cox 比例风险模型，对年龄、性别、吸烟史、抗 MDA5 抗体滴度和同时使用其他类固醇节省药物进行调整，比较两组全因死亡率，并探讨预测两组 1 年死亡率的危险因素。
在研究期间，26 例患者接受 TOF 治疗，35 例患者接受 TAC 治疗。TOF 组的 6 个月（38.5%比 62.9%；=0.03）和 1 年（44.0%比 65.7%；=0.03）死亡率显著低于 TAC 组。TOF 组中有 13 例诊断为快速进展性ILD（RP-ILD），TAC 组中有 22 例。大多数死亡发生在 RP-ILD 患者中。TOF 组 RP-ILD 患者的 6 个月（76.9%比 95.5%；=0.02）和 1 年（84.6%比 100.0%；=0.02）死亡率也低于 TAC 组。调整模型显示，TOF 暴露与 1 年死亡率降低相关（风险比 0.44，95%CI 0.20-0.96；=0.04）。然而，TOF 和 TAC 组的不良事件发生率（73.1%比 74.3%；>0.99）和停药率（23.1%比 14.3%；=0.50）相似。
我们的观察性研究表明，TOF 可能对改善 MDA5-ILD 的结局有潜在影响。需要进一步的临床试验来评估 TOF 的长期疗效和耐受性。
