Journal of Clinical Immunology ( IF 7.2 ) Pub Date : 2020-11-04 , DOI: 10.1007/s10875-020-00901-8 Anne Conrad 1, 2 , Bénédicte Neven 3, 4, 5 , Nizar Mahlaoui 3, 6 , Felipe Suarez 5, 6, 7, 8 , Harry Sokol 9 , Frank M Ruemmele 10 , Claire Rouzaud 1 , Despina Moshous 3, 4, 5 , Olivier Lortholary 1, 5 , Stéphane Blanche 3, 4, 5 , Fanny Lanternier 1, 5
Purpose
Management of inflammatory complications of chronic granulomatous disease (CGD) is challenging. The aim of this study was to assess safety, with a focus on infections, and effectiveness of tumor necrosis factor alpha (TNF-α) blockers in CGD patients.
Methods
A retrospective, single-center cohort study of CGD patients treated by anti-TNF-α agents at Necker-Enfants Malades University Hospital (Paris, France) and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH).
Results
Between 2006 and 2019, 14 (X-linked: n = 10, 71.4%; autosomal-recessive: n = 4, 28.6%) CGD patients with gastrointestinal (n = 12, 85.7%), pulmonary (n = 10, 71.4%), cutaneous (n = 3, 21.4%), and/or genitourinary (n = 2, 14.3%) inflammatory manifestations received one or more doses of infliximab because of steroid-dependent (n = 7, 50%), refractory (n = 4, 28.6%) inflammatory disease or as first-line drug (n = 2, 14.3%; missing data, n = 1). All patients received adequate antimicrobial prophylaxis. Infliximab achieved complete (n = 2, 14.3%) or partial (n = 9, 64.3%) response in 11 (78.6%) patients. Seven (50%) patients were switched to adalimumab. During anti-TNF-α treatment, 11 infections (pneumonia, adenitis, invasive candidiasis, each n = 2; intra-abdominal abscess, bacteremic salmonellosis, Pseudomonas aeruginosa–related folliculitis, cat-scratch disease, proven pulmonary mucormycosis, each n = 1) occurred in 7 (50%) patients. All infectious complications had a favorable outcome. Anti-TNF-α treatment was definitively stopped because of infection in two patients. Nine (64.3%) patients finally underwent hematopoietic stem cell transplantation. No death occurred during follow-up.
Conclusions
Anti-TNF-α treatment could improve the outcome of severe inflammatory complications in CGD patients, but increases their risk of infections. We suggest that anti-TNF-α treatment might be of short-term benefit in selected CGD patients with severe inflammatory complications awaiting hematopoietic stem cell transplantation.
中文翻译:
用肿瘤坏死因子 α 阻滞剂治疗炎症并发症的慢性肉芽肿病患者的感染
目的
慢性肉芽肿病 (CGD) 炎症并发症的管理具有挑战性。本研究的目的是评估 CGD 患者中肿瘤坏死因子 α (TNF-α) 阻滞剂的安全性,重点是感染和有效性。
方法
一项回顾性、单中心队列研究,针对在 Necker-Enfants Malades 大学医院(法国巴黎)接受抗 TNF-α 药物治疗并在法国国家原发性免疫缺陷参考中心 (CEREDIH) 注册的 CGD 患者。
结果
2006 年至 2019 年间,14 名(X 连锁:n = 10, 71.4%;常染色体隐性遗传:n = 4, 28.6%)CGD 患者伴有胃肠道(n = 12, 85.7%)、肺部(n = 10, 71.4% ) )、皮肤 ( n = 3, 21.4%) 和/或泌尿生殖系统 ( n = 2, 14.3%) 炎症表现因类固醇依赖性 ( n = 7, 50%)、难治性 ( n = 4, 28.6%)炎症性疾病或作为一线药物(n = 2, 14.3%;缺失数据,n = 1)。所有患者都接受了充分的抗菌预防。英夫利昔单抗达到完全(n = 2, 14.3%)或部分(n = 9, 64.3%) 11 名 (78.6%) 患者的反应。七名 (50%) 患者改用阿达木单抗。在抗 TNF-α 治疗期间,11 例感染(肺炎、腺炎、侵袭性念珠菌病,每个n = 2;腹腔内脓肿、细菌性沙门氏菌病、铜绿假单胞菌相关毛囊炎、猫抓病、确诊的肺毛霉菌病,每个n = 1 ) 发生在 7 (50%) 名患者中。所有感染性并发症都有良好的结果。由于两名患者感染,最终停止了抗 TNF-α 治疗。9 名(64.3%)患者最终接受了造血干细胞移植。随访期间未发生死亡。
结论
抗 TNF-α 治疗可以改善 CGD 患者严重炎症并发症的结果,但会增加他们感染的风险。我们建议,对于等待造血干细胞移植的严重炎症并发症的选定 CGD 患者,抗 TNF-α 治疗可能具有短期益处。