Department of Rheumatology, Dokkyo Medical University, Tochigi, Japan.
Rheumatology (Oxford). 2018 Dec 1;57(12):2114-2119. doi: 10.1093/rheumatology/key188.
We aimed to determine the outcome of combination therapy with tofacitinib (TOF) in a case series of refractory rapidly progressive interstitial lung disease (ILD) associated with anti-melanoma differentiation-associated 5 gene (MDA5) antibody-positive (Ab+) DM. Patients who had poor prognostic factors and failed to respond to immunosuppressive therapy were selected for TOF treatment.
Five patients with anti-MDA5 Ab+ DM-ILD who failed to respond to triple therapy with high dose glucocorticoids, CSA and CYC were given additional TOF (10 mg/day). To identify the poor prognostic factors, data from 15 consecutive patients (seven survived and eight died) with anti-MDA5 Ab+ DM-ILD before induction of TOF were analysed.
Three poor prognostic factors were identified: serum ferritin level >1000 ng/ml before therapy; ground-glass opacities in all six lung fields before therapy; and worsening of pulmonary infiltrates during therapy. All six patients who had all of the three factors and received triple therapy died before TOF therapy. There were five patients who had all of the three prognostic factors and failed to respond to triple therapy, but were able to receive the combination therapy with TOF; among them, three survived and two died. The survival rate of patients who received TOF was significantly better than that of the historical controls with immunosuppressive therapy before TOF. The patients who received TOF experienced complicated adverse events, particularly viral infection.
Combination therapy with TOF might have the potential to control refractory anti-MDA5 Ab+ DM-ILD.
我们旨在确定托法替尼（TOF）联合治疗在抗黑色素瘤分化相关 5 基因（MDA5）抗体阳性（Ab+）DM 相关难治性快速进展性间质性肺病（ILD）病例系列中的疗效。选择具有不良预后因素且对免疫抑制治疗无反应的患者进行 TOF 治疗。
5 例对高剂量糖皮质激素、CSA 和 CYC 三联疗法无反应的抗-MDA5 Ab+DM-ILD 患者加用 TOF（10mg/天）。为了确定不良预后因素，对 15 例连续的抗-MDA5 Ab+DM-ILD 患者（7 例存活，8 例死亡）在开始 TOF 治疗前的数据进行了分析。
确定了 3 个不良预后因素：治疗前血清铁蛋白水平>1000ng/ml；治疗前 6 个肺野均有磨玻璃影；治疗过程中肺部浸润加重。所有 6 例均有这 3 个因素且接受三联治疗的患者在接受 TOF 治疗前均死亡。有 5 例患者具有所有这 3 个预后因素且对三联治疗无反应，但能够接受 TOF 联合治疗；其中 3 例存活，2 例死亡。接受 TOF 治疗的患者的存活率明显高于接受 TOF 治疗前的免疫抑制治疗的历史对照。接受 TOF 治疗的患者出现了复杂的不良反应，特别是病毒感染。
TOF 联合治疗可能有潜力控制难治性抗-MDA5 Ab+DM-ILD。
