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：

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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。