Rheumatology Unit, Department of Medicine DIMED, University of Padova, Italy.
Clin Exp Rheumatol. 2020 Mar-Apr;38 Suppl 124(2):188-194. Epub 2020 May 22.
The burden of hypogammaglobulinaemia following rituximab (RTX) treatment in rheumatic diseases has not been fully elucidated yet. Our aim was to evaluate the frequency and predictors of hypogammaglobulinaemia in patients affected by ANCA-associated vasculitis (AAV) and connective tissue diseases (CTD).
We retrospectively reviewed prospectively collected data of patients receiving RTX. Immunoglobulins (Ig) levels and lymphocyte subsets were recorded at RTX administration and 3-6 months later. We assessed frequency of hypogammaglobulinaemia (serum IgG<6 g/L) and its related events. Univariate and multivariable analysis were performed using SPSS 20.0 package.
Sixty-eight patients (30 AAV, 25 systemic lupus erythematosus, 9 systemic sclerosis and 4 idiopathic inflammatory myopathies) were treated with RTX (95 infusions, median 2 [2-6]). Following RTX, IgG<6 g/L were observed in 15/68 patients (15.8%), IgM<0.4 g/L in 28/68 (41%) and IgA<0.7 g/L in 7/68 (10.2%). Hypogammaglobulinaemia was more common in patients with AAV (p=0.008), short disease duration (p=0.001), low IgG levels at baseline (p=0.008), high cyclophosphamide exposure (p=0.018), high daily and cumulative prednisone dosage (p=0.001 and p=0.006). At multivariate analysis, cumulative cyclophosphamide dosage (OR 1.1 [1.0-1.3] p=0.045), daily prednisone intake >15mg (OR 9.5 [2.2-41.7] p=0.03) and IgG levels before RTX (OR 0.74 [0.59-0.93] p=0.009) were independent predictors of hypogammaglobulinaemia. Five patients experienced severe infections within 12 months, more frequently in those with IgG<6 g/L (26.7% vs 1.9%, p=0.007).
Hypogammaglobulinaemia following RTX is uncommon in AAV and CTD and is more likely in patients with high glucocorticoids and cyclophosphamide exposure and low IgG levels at baseline.
利妥昔单抗（RTX）治疗后低丙种球蛋白血症的负担尚未完全阐明。我们的目的是评估抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）和结缔组织疾病（CTD）患者中低丙种球蛋白血症的频率和预测因素。
我们回顾性分析了接受 RTX 治疗的患者前瞻性收集的数据。在 RTX 给药时和 3-6 个月后记录免疫球蛋白（Ig）水平和淋巴细胞亚群。我们评估了低丙种球蛋白血症（血清 IgG<6 g/L）及其相关事件的频率。使用 SPSS 20.0 软件包进行单变量和多变量分析。
68 例患者（30 例 AAV、25 例系统性红斑狼疮、9 例系统性硬化症和 4 例特发性炎性肌病）接受 RTX 治疗（95 次输注，中位数 2[2-6]）。RTX 后，68 例患者中有 15/68（15.8%）患者 IgG<6 g/L，28/68（41%）患者 IgM<0.4 g/L，7/68（10.2%）患者 IgA<0.7 g/L。AAV 患者低丙种球蛋白血症更常见（p=0.008），疾病病程较短（p=0.001），基线时 IgG 水平较低（p=0.008），环磷酰胺暴露量较高（p=0.018），每日和累积泼尼松剂量较高（p=0.001 和 p=0.006）。多变量分析显示，累积环磷酰胺剂量（OR 1.1[1.0-1.3]，p=0.045）、每日泼尼松摄入>15mg（OR 9.5[2.2-41.7]，p=0.03）和 RTX 前 IgG 水平（OR 0.74[0.59-0.93]，p=0.009）是低丙种球蛋白血症的独立预测因素。5 例患者在 12 个月内发生严重感染，IgG<6 g/L 患者更常见（26.7% vs 1.9%，p=0.007）。
RTX 后 AAV 和 CTD 患者低丙种球蛋白血症并不常见，高糖皮质激素和环磷酰胺暴露以及基线时 IgG 水平较低的患者更有可能发生低丙种球蛋白血症。
