Division of Immunodeficiency, Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Division of Immunodeficiency, Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
J Allergy Clin Immunol Pract. 2021 Feb;9(2):760-770.e10. doi: 10.1016/j.jaip.2020.10.028. Epub 2020 Oct 24.
Interstitial lung disease (ILD) represents a severe clinical manifestation of systemic immune dysregulation in patients with common variable immunodeficiency (CVID). Its treatment often requires systemic immunosuppression beyond corticosteroids.
To assess the safety and efficacy of abatacept in patients with CVID and ILD.
Ten patients with confirmed diagnosis of CVID and ILD were included in a single-center, prospective, open-label, nonrandomized trial. Abatacept was administered subcutaneously at a dose of 125 mg/wk for 12 months.
Abatacept was a safe treatment for ILD in CVID except for 1 case of bronchopulmonary aspergillosis. One additional patient terminated the trial prematurely because of recurrent bronchitis. Five of 8 patients treated per protocol benefited from the treatment according to American Thoracic Society/European Respiratory Society criteria. The primary end point of the study was met because single breath diffusing capacity of the lung for carbon monoxide was stable (62.5%) or improved (37.5%) in all patients treated per protocol. Although nodules (71%) and ground-glass opacities (57%) improved in most patients, other computed tomography pathologies were less responsive. Quality of life improved in 87.5% and fatigue in 57% of patients. Abatacept treatment was associated with significant improvement in CD4 T-cell dysregulation, signified by a decrease in serum soluble IL-2 receptor levels and of proliferating Ki67 CD4 T cells, and a recovery of total lymphocytes, CD4 T cells, and naive CD4 T cells.
Abatacept may represent a treatment option for CVID-associated ILD. This pilot study demonstrated a good safety profile, steroid-sparing effect, positive immune modulation, and overall positive treatment response especially in quality of life. Larger controlled studies are needed to confirm these findings.
间质性肺病（ILD）代表了普通变异性免疫缺陷（CVID）患者全身免疫失调的严重临床表现。其治疗通常需要超越皮质类固醇的全身性免疫抑制。
评估阿巴西普在 CVID 和ILD 患者中的安全性和疗效。
10 例确诊为 CVID 和ILD 的患者纳入单中心、前瞻性、开放标签、非随机试验。阿巴西普以 125mg/周的剂量皮下给药，持续 12 个月。
除 1 例支气管肺曲霉病外，阿巴西普治疗 CVID 的ILD 是安全的。由于复发性支气管炎，另外 1 名患者提前终止试验。根据美国胸科学会/欧洲呼吸学会标准，8 名按方案治疗的患者中有 5 名受益于治疗。该研究的主要终点得到满足，因为所有按方案治疗的患者的肺一氧化碳弥散量均保持稳定（62.5%）或改善（37.5%）。尽管大多数患者的结节（71%）和磨玻璃影（57%）有所改善，但其他 CT 病理反应较差。87.5%的患者生活质量改善，57%的患者疲劳改善。阿巴西普治疗与 CD4 T 细胞失调的显著改善相关，表现为血清可溶性 IL-2 受体水平和增殖 Ki67 CD4 T 细胞下降，以及总淋巴细胞、CD4 T 细胞和幼稚 CD4 T 细胞恢复。
阿巴西普可能是治疗 CVID 相关 ILD 的一种选择。这项初步研究显示了良好的安全性、类固醇节约效应、积极的免疫调节作用，特别是在生活质量方面的总体积极治疗反应。需要更大的对照研究来证实这些发现。
