Smith Rona M, Jones Rachel B, Guerry Mary-Jane, Laurino Simona, Catapano Fausta, Chaudhry Afzal, Smith Kenneth G C, Jayne David R W
Addenbrooke's Hospital, Cambridge, UK.
Arthritis Rheum. 2012 Nov;64(11):3760-9. doi: 10.1002/art.34583.
Rituximab is effective induction therapy in refractory or relapsing antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, further relapse is common, and maintenance strategies are required. The aim of this study was to reduce relapse rates using a fixed-interval rituximab re-treatment protocol.
Retrospective, standardized collection of data from sequential patients receiving rituximab for refractory or relapsing AAV at a single center was studied. Group A patients (n = 28) received rituximab induction therapy (4 infusions of 375 mg/m(2) or 2 infusions 1 gm) and further rituximab at the time of subsequent relapse. Group B patients (n = 45) received routine rituximab re-treatment for 2 years: 2 doses of 1 gm each for remission induction, then 1 gm every 6 months (total of 6 gm). Group C patients (n = 19) comprised patients in group A who subsequently relapsed and began routine re-treatment for 2 years.
Response (complete/partial remission) occurred in 26 of the 28 patients (93%) in group A, 43 of the 45 patients (96%) in group B, and 18 of the 19 patients (95%) in group C. At 2 years, relapses had occurred in 19 of 26 patients (73%) in group A, 5 of 43 (12%) in group B (P < 0.001), and 2 of 18 (11%) in group C (P < 0.001). At the last followup (median of 44 months), relapses had occurred in 85% of those in group A (22 of 26), 26% of those in group B (11 of 43; P < 0.001), and 56% of those in group C (10 of 18; P = 0.001). Glucocorticoid dosages were decreased and immunosuppression therapy was withdrawn in the majority of patients. Routine rituximab re-treatment was well tolerated, and no new safety issues were identified.
Two-year, fixed-interval rituximab re-treatment was associated with a reduction in relapse rates during the re-treatment period and a more prolonged period of remission during subsequent followup. In the absence of biomarkers that accurately predict relapse, routine rituximab re-treatment may be an effective strategy for remission maintenance in patients with refractory and relapsing AAV.
利妥昔单抗是难治性或复发性抗中性粒细胞胞浆抗体相关性血管炎（AAV）的有效诱导治疗药物。然而，进一步复发很常见，需要维持治疗策略。本研究的目的是使用固定间隔的利妥昔单抗再治疗方案降低复发率。
对在单一中心接受利妥昔单抗治疗难治性或复发性AAV的连续患者进行回顾性、标准化数据收集。A组患者（n = 28）接受利妥昔单抗诱导治疗（4次输注，375 mg/m²，或2次输注，1 g），并在随后复发时再次使用利妥昔单抗。B组患者（n = 45）接受为期2年的常规利妥昔单抗再治疗：诱导缓解时给予2剂，各1 g，然后每6个月1 g（共6 g）。C组患者（n = 19）包括A组中随后复发并开始为期2年常规再治疗的患者。
A组28例患者中有26例（93%）出现缓解（完全/部分缓解），B组45例患者中有43例（96%），C组19例患者中有18例（95%）。2年时，A组26例患者中有19例（73%）复发，B组43例中有5例（12%）（P < 0.001），C组18例中有2例（11%）（P < 0.001）。在最后一次随访时（中位随访44个月），A组85%的患者（26例中的22例）复发，B组26%的患者（43例中的11例；P < 0.001），C组56%的患者（18例中的10例；P = 0.001）。大多数患者的糖皮质激素剂量减少，免疫抑制治疗停用。常规利妥昔单抗再治疗耐受性良好，未发现新的安全问题。
为期2年的固定间隔利妥昔单抗再治疗与再治疗期间复发率降低以及随后随访期间缓解期延长相关。在缺乏准确预测复发的生物标志物的情况下，常规利妥昔单抗再治疗可能是难治性和复发性AAV患者缓解维持的有效策略。
