Department of Dermatology, CAC ICBAS-CHP - Centro Académico Clínico ICBAS - CHP, Rua D. Manuel II, s/n, 4100, Porto, Portugal.
UMIB - Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
Am J Clin Dermatol. 2024 Mar;25(2):333-342. doi: 10.1007/s40257-024-00845-4. Epub 2024 Jan 24.
Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation.
To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis.
This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded.
A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant).
The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.
结核病在全球范围内有重大影响。免疫功能正常的宿主通常可以控制这种疾病,导致无症状的潜伏性结核感染(LTBI)。由于 TNF 抑制剂会增加结核再激活的风险,因此现行指南建议在开始使用任何生物药物之前进行结核筛查,如果诊断为 LTBI,则进行化学预防。来自临床试验和真实世界研究的现有证据表明,IL-17 和 IL-23 抑制剂不会增加结核再激活的风险。
评估接受 IL-17 和 IL-23 抑制剂治疗的或未经治疗的新诊断 LTBI 的银屑病患者,以及结核化学预防的耐受性/安全性。
这是一项回顾性、观察性、多国研究,来自葡萄牙、西班牙、意大利、希腊和巴西的 14 个皮肤科中心系列,纳入了患有中重度慢性斑块型银屑病且新诊断为 LTBI 的成年患者,他们在 2015 年 1 月至 2022 年 3 月期间接受了 IL-23 或 IL-17 抑制剂治疗。LTBI 的诊断依据是根据当地指南,在开始使用 IL-23 或 IL-17 抑制剂之前,结核菌素皮肤试验和/或干扰素释放试验阳性。排除了既往诊断为 LTBI(已治疗或未治疗)或治疗活动性感染的患者。
共纳入 405 例患者;分别有 62.2%、10.1%和 27.7%的患者接受了完整/不完整/未进行化学预防。不接受或中断化学预防的主要原因分别是认为存在肝毒性和肝毒性的风险增加。生物治疗的平均持续时间为 32.87±20.95 个月,仅观察到 1 例活动性结核感染(ATBI),发生在使用依奇珠单抗治疗 14 个月后。依奇珠单抗相关 ATBI 的比例为 1.64%[95%置信区间(CI):0-5.43%],所有其他药物的比例为 0%,IL-17 和 IL-23 抑制剂的比例分别为 0.46%(95%CI 0-1.06%)和 0%(无统计学意义)。
LTBI 合并银屑病患者的结核再激活风险似乎不会因 IL-17 或 IL-23 抑制剂而增加。当存在结核再激活的顾虑时,IL-17 或 IL-23 抑制剂应优于 TNF 拮抗剂。对于考虑因化学预防而发生相关并发症风险较高的 LTBI 患者,在开始使用 IL-17 抑制剂,尤其是 IL-23 抑制剂治疗之前,可以放弃这种预防策略。