Md Yusof Md Yuzaiful, Iqbal Kundan, Darby Michael, Lettieri Giovanni, Vital Edward M, Beirne Paul, Dass Shouvik, Emery Paul, Kelly Clive
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton HospitalLeeds, UK.
NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, LeedsUK.
Rheumatology (Oxford). 2020 Oct 1;59(10):2838-2846. doi: 10.1093/rheumatology/kez676.
To evaluate rituximab (RTX) in patients with RA-associated bronchiectasis (RA-BR) and compare 5-year respiratory survival between those treated with RTX and TNF inhibitors (TNFi).
A retrospective observational cohort study of RA-BR in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbation/year. Respiratory survival was measured from therapy initiation to discontinuation either due to lung exacerbation or lung-related deaths.
Of 800 RTX-treated RA patients, 68 had RA-BR (prevalence 8.5%). Post-RTX, new BR was diagnosed in 3/735 patients (incidence 0.4%). At 12 months post-Cycle 1 RTX, 21/68 (31%) patients had fewer exacerbations than the year pre-RTX, 36/68 (53%) remained stable and 11/68 (16%) had increased exacerbations. The rates of exacerbation improved after Cycle 2 and stabilized up to 5 cycles. Of patients who received ≥2 RTX cycles (n = 60), increased exacerbations occurred in 7/60 (12%) and were associated with low IgG, aspergillosis and concurrent alpha-1-antitrypsin deficiency. Overall, 8/68 (11.8%) patients discontinued RTX while 15/46 (32.6%) discontinued TNFi due to respiratory causes. The adjusted 5-year respiratory survival was better in RTX-treated compared with TNFi-treated RA-BR patients; HR 0.40 (95% CI 0.17, 0.96); P =0.041.
The majority of RTX-treated RA-BR patients had stable/improved pulmonary symptoms in this long-term follow-up. In isolated cases, worsening of exacerbation had definable causes. Rates of discontinuation due to adverse lung outcomes were better for RTX than a matched TNFi cohort. RTX is an acceptable therapeutic choice for RA-BR if a biologic is needed.
评估利妥昔单抗(RTX)用于类风湿关节炎相关支气管扩张症(RA - BR)患者的疗效,并比较接受RTX治疗与肿瘤坏死因子抑制剂(TNFi)治疗的患者5年的呼吸生存率。
一项对来自英国两个中心的接受RTX或TNFi治疗的类风湿关节炎患者中RA - BR进行的回顾性观察队列研究,为期10年。使用每年感染性加重次数评估支气管扩张症。呼吸生存率从治疗开始至因肺部加重或肺部相关死亡而停药进行测量。
在800例接受RTX治疗的类风湿关节炎患者中,68例患有RA - BR(患病率8.5%)。RTX治疗后,735例患者中有3例被诊断为新发支气管扩张症(发病率0.4%)。在第1周期RTX治疗后12个月时,68例患者中有21例(31%)加重次数少于RTX治疗前一年,36例(53%)病情稳定,11例(16%)加重次数增加。第2周期后加重率有所改善,并在多达5个周期时保持稳定。在接受≥2个RTX周期治疗的患者(n = 60)中,7例(12%)加重次数增加,且与低IgG、曲霉病和并发α-1抗胰蛋白酶缺乏有关。总体而言,68例患者中有8例(11.8%)因呼吸原因停用RTX,而46例接受TNFi治疗的患者中有15例(32.6%)因呼吸原因停药。与接受TNFi治疗的RA - BR患者相比,接受RTX治疗的患者调整后的5年呼吸生存率更好;风险比0.40(95%置信区间0.17,0.96);P = 0.041。
在这项长期随访中,大多数接受RTX治疗的RA - BR患者肺部症状稳定/改善。在个别病例中,加重恶化有明确原因。与匹配的TNFi队列相比,RTX因不良肺部结局导致停药的发生率更低。如果需要使用生物制剂,RTX是RA - BR可接受的治疗选择。