Timlin H, Lee S M, Manno R L, Seo P, Geetha Duvura
Johns Hopkins Bayview Medical Center, Division of Renal Medicine, 301 Mason Lord Drive, Baltimore, MD 21224.
Johns Hopkins Bayview Medical Center, Division of Renal Medicine, 301 Mason Lord Drive, Baltimore, MD 21224.
Semin Arthritis Rheum. 2015 Aug;45(1):67-9. doi: 10.1016/j.semarthrit.2015.02.005. Epub 2015 Feb 20.
Advancing age is a risk factor for treatment-related side effects and mortality in AAV patients treated with cyclophosphamide (CYC) and glucocorticoids (GC) for remission induction. The efficacy and safety of rituximab (RTX) in elderly AAV patients has not been well described.
We performed a single center retrospective review of 31 consecutive AAV patients aged 60 or more at the time of RTX use for remission induction. All patients received RTX with GC for remission induction. Four patients received concomitant CYC for a mean duration of 52 days. We evaluated clinical and laboratory variables at diagnosis, rates of complete remission defined as Birmingham Vasculitis Activity Score/Wegener's Granulomatosis (BVAS/WG) = 0 and patient survival, renal survival, infections requiring hospitalization, and vasculitis relapse 24 months following RTX use.
Of the 31 patients, 77% were Caucasian, 68% female, mean age was 71 ± 6 years, 58% were MPO ANCA positive, and 42% had relapsing disease. The mean BVAS/WG score entry was 4.4 ± 1.5, 71% had glomerulonephritis (GN) and 10% had alveolar hemorrhage. The mean baseline e-GFR was 40 ± 28ml/min/1.73m(2). Thirty patients achieved remission with a mean time to remission of 57 ± 27 days. The single patient with refractory vasculitis responded to CYC. The mean prednisone dose at 6 months was 5.6 ± 4mg. Remission maintenance therapy was started within 12 months of RTX induction in 6 patients (4 with RTX, 1 with azathioprine, and 1 with mycophenolate mofetil). One patient suffered a limited relapse 10 months post RTX use. Among the 22 patients with GN at baseline, 1 developed ESRD. One-year patient survival among 25 patients with at least 1 year of follow-up was 100%. There were no episodes of infusion reaction or leukopenia. There were 3 episodes of bacterial pneumonia, 1 episode of candida pneumonia, and 1 episode of disseminated cutaneous zoster.
This study demonstrates that rituximab is effective for remission induction in elderly patients with AAV. Furthermore, we observed a high incidence of infectious complications. Our experience was limited by its retrospective design, and further studies are needed to evaluate the efficacy and safety of RTX in elderly AAV patients.
在接受环磷酰胺(CYC)和糖皮质激素(GC)诱导缓解治疗的抗中性粒细胞胞浆抗体相关血管炎(AAV)患者中,年龄增长是治疗相关副作用和死亡的危险因素。利妥昔单抗(RTX)在老年AAV患者中的疗效和安全性尚未得到充分描述。
我们对31例连续使用RTX诱导缓解时年龄在60岁及以上的AAV患者进行了单中心回顾性研究。所有患者接受RTX联合GC诱导缓解。4例患者同时接受CYC治疗,平均疗程为52天。我们评估了诊断时的临床和实验室变量、定义为伯明翰血管炎活动评分/韦格纳肉芽肿(BVAS/WG)=0的完全缓解率、患者生存率、肾脏生存率、需要住院治疗的感染以及RTX使用后24个月的血管炎复发情况。
31例患者中,77%为白种人,68%为女性,平均年龄为71±6岁,58%为髓过氧化物酶抗中性粒细胞胞浆抗体(MPO-ANCA)阳性,42%为复发性疾病。BVAS/WG评分的平均基线值为4.4±1.5,71%有肾小球肾炎(GN),10%有肺泡出血。平均基线估算肾小球滤过率(e-GFR)为40±28ml/min/1.73m²。30例患者实现缓解,平均缓解时间为57±27天。1例难治性血管炎患者对CYC有反应。6个月时泼尼松的平均剂量为5.6±4mg。6例患者(4例使用RTX,1例使用硫唑嘌呤,1例使用霉酚酸酯)在RTX诱导后12个月内开始缓解维持治疗。1例患者在RTX使用后10个月出现有限复发。在基线时有GN的22例患者中,1例发展为终末期肾病(ESRD)。在25例至少随访1年的患者中一年生存率为100%。没有输注反应或白细胞减少的发作。有3次细菌性肺炎发作、1次念珠菌肺炎发作和1次播散性带状疱疹发作。
本研究表明,利妥昔单抗对老年AAV患者诱导缓解有效。此外,我们观察到感染并发症的发生率较高。我们的经验受其回顾性设计的限制,需要进一步研究来评估RTX在老年AAV患者中的疗效和安全性。