Conticini Edoardo, Cameli Paolo, Grazzini Silvia, d'Alessandro Miriana, Bergantini Laura, Pianigiani Tommaso, Guarnieri Andrea, Mancianti Nicoletta, Fabiani Claudia, Cantarini Luca, Bargagli Elena, Frediani Bruno
Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy.
Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy.
Respir Med. 2025 Nov;248:108334. doi: 10.1016/j.rmed.2025.108334. Epub 2025 Aug 29.
The prevalence of interstitial lung disease (ILD) in ANCA associated vasculitis (AAV) ranges from 13 % to 45 %, and both its definition and management represent a quandary. The occurrence of lung fibrosis and ANCA positivity, particularly in subjects without any other evidence of vasculitis, is far from being clearly interpreted, as well as its proper therapeutic management. In this regard, aim of this study is to assess whether Rituximab (RTX) in association with a low dosage of glucocorticoids (GCs), could be effective also in the treatment of AAV-ILD.
We prospectively included all patients referred to our multidisciplinary "Vasculitis with lung involvement clinic" from January 2022 to March 2023 with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA), ANCA positivity and ILD. All patients were concomitantly evaluated by a rheumatologist and a pneumologist experienced in vasculitis and autoimmune-associated ILD. High resolution computed tomography (HRCT) of the chest was performed at baseline and then after 12 months, while lung function test (LFT), including diffusion lung capacity for CO (DLCO) assessment, at baseline and after 6 and 12 months. For induction of remission, patients were treated with RTX, administered with the two-dose protocol (1000 mg at baseline and after 14 days) approved for rheumatoid arthritis, followed by 500 mg every 6 months. GCs were prescribed and then tapered according to PEXIVAS trial.
Eight patients, 3 affected by GPA and 5 by MPA, were included. All but one displayed positivity for anti-MPO and 3 of them did not have any extra-pulmonary sign of vasculitis. At baseline, LFT evidenced a restrictive pattern (mean FVC 83 %) associated with a moderate impairment of diffusion capacity (mean DLCO 54 %). After 6 and 12 months, a stabilization of LFT findings was evidenced, while no sign of progression of ILD was assessed at CT scan. No patient suffered from severe AE, except one who had bacterial pneumonia. All patients but three discontinued GCs.
Ours represents the first prospective study specifically designed to evaluate the efficacy of RTX in AAV-ILD. Our findings have displayed that RTX, prescribed in association with a short course of GCs, is able to stabilize imaging features and respiratory functional parameters.
抗中性粒细胞胞浆抗体相关性血管炎（AAV）中间质性肺疾病（ILD）的患病率在13%至45%之间，其定义和管理都存在难题。肺纤维化和抗中性粒细胞胞浆抗体阳性的出现，尤其是在没有任何其他血管炎证据的患者中，以及其恰当的治疗管理，都远未得到明确解释。在这方面，本研究的目的是评估利妥昔单抗（RTX）联合低剂量糖皮质激素（GCs）是否也能有效治疗AAV-ILD。
我们前瞻性纳入了2022年1月至2023年3月期间转诊至我们多学科“肺部受累血管炎诊所”的所有患有显微镜下多血管炎（MPA）或肉芽肿性多血管炎（GPA）、抗中性粒细胞胞浆抗体阳性和ILD的患者。所有患者均由一位在血管炎和自身免疫相关ILD方面经验丰富的风湿病学家和一位肺科医生同时进行评估。在基线时以及12个月后进行胸部高分辨率计算机断层扫描（HRCT），同时在基线时以及6个月和12个月后进行肺功能测试（LFT），包括一氧化碳弥散肺容量（DLCO）评估。为诱导缓解，患者接受RTX治疗，采用类风湿关节炎批准的两剂量方案（基线时和14天后各1000mg），随后每6个月500mg。根据PEXIVAS试验开具GCs并逐渐减量。
纳入8例患者，其中3例为GPA，5例为MPA。除1例患者外，所有患者抗髓过氧化物酶（MPO）均呈阳性，其中3例没有任何肺外血管炎体征。基线时，LFT显示为限制性模式（平均用力肺活量[FVC]为83%），伴有中度弥散功能损害（平均DLCO为54%）。6个月和12个月后，LFT结果显示稳定，而CT扫描未评估到ILD进展的迹象。除1例患有细菌性肺炎的患者外，没有患者发生严重不良事件（AE）。除3例患者外，所有患者均停用了GCs。
我们的研究是第一项专门设计用于评估RTX在AAV-ILD中疗效的前瞻性研究。我们的研究结果表明，与短期GCs联合使用的RTX能够稳定影像学特征和呼吸功能参数。
