J.M. Springer, Associate Professor, MD, MS, Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
R.S. Funk, Associate Professor, PharmD, PhD, Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City, Kansas, USA.
J Rheumatol. 2021 Nov;48(11):1718-1724. doi: 10.3899/jrheum.210361. Epub 2021 Aug 1.
Rituximab (RTX) is effective in the induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV.
A prospective cohort of patients with AAV (n = 28) with either granulomatosis with polyangiitis (n = 23) or microscopic polyangiitis (n = 5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B cell counts and ANCA titers.
RTX dosing information from 94 infusions with 59 trough samples were collected with a mean ± SD dose of 640 ± 221 mg, dosing interval of 210 ± 88 days, and trough plasma RTX concentration of 622 ± 548 ng/mL. RTX trough concentrations were associated with RTX dose (ρ = 0.60, < 0.0001) and dosing interval (ρ = -0.55, < 0.0001). RTX dosing intensity (mg/d) was associated with RTX trough concentrations (ρ = 0.57, < 0.0001). Higher dosing intensities were associated with undetectable B cell repopulation ( < 0.0001), but not negative ANCA titers ( = 0.60). Stratification of dosing intensities based on the standard dosing regimen of 500 mg every 6 months (2.4-3.3 mg/d) demonstrated that this regimen was associated with B cell repopulation in 8 of 17 doses (47%) compared to 0 of 23 doses (0%) with the high-dose regimen (> 3.3 mg/d; < 0.0001).
RTX maintenance dosing of 500 mg every 6 months may be inadequate to maintain B cell depletion in the treatment of AAV.
利妥昔单抗（RTX）在抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）的诱导和缓解维持中有效。然而，最佳维持剂量方案仍存在不确定性。本研究评估了 AAV 中 RTX 剂量变异性与药物反应之间的关系。
前瞻性队列研究纳入在单家三级学术医疗中心接受维持 RTX 治疗的 28 例 AAV 患者（n=28），其中包括肉芽肿性多血管炎（n=23）或显微镜下多血管炎（n=5）。在 2 年的随访期间，收集患者的人口统计学、RTX 剂量信息和最低点血浆 RTX 水平，以及包括 B 细胞计数和 ANCA 滴度在内的药物反应的实验室测量结果。
共收集了 94 次输注和 59 次最低点样本的 RTX 剂量信息，平均剂量±标准差为 640±221mg，给药间隔为 210±88 天，最低点血浆 RTX 浓度为 622±548ng/mL。RTX 最低点浓度与 RTX 剂量（ρ=0.60，<0.0001）和给药间隔（ρ=-0.55，<0.0001）相关。RTX 给药强度（mg/d）与 RTX 最低点浓度相关（ρ=0.57，<0.0001）。更高的给药强度与不可检测的 B 细胞再增殖相关（<0.0001），但与阴性 ANCA 滴度无关（=0.60）。基于每 6 个月 500mg 的标准剂量方案（2.4-3.3mg/d）进行剂量强度分层，结果显示，该方案与 17 次剂量中的 8 次（47%）B 细胞再增殖相关，而与 23 次剂量中的 0 次（0%）高剂量方案（>3.3mg/d；<0.0001）相关。
每 6 个月 500mg 的 RTX 维持剂量可能不足以维持 AAV 治疗中的 B 细胞耗竭。
