Puig L, Tsai T-F, Bhutani T, Uy J, Ramachandran P, Song M, You Y, Gooderham M, Lebwohl M
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
National Taiwan University Hospital, Taipei, Taiwan.
J Eur Acad Dermatol Venereol. 2020 Aug;34(8):1744-1749. doi: 10.1111/jdv.16460. Epub 2020 May 15.
Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new-onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)-23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics.
Safety in moderate-to-severe psoriasis patients with LTBI treated with guselkumab (IL-23 inhibitor) and LTBI treatment was evaluated.
In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo → guselkumab crossover occurred at week 16 and adalimumab → guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab-treated patients receiving and not receiving LTBI treatment.
At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab-treated patients without LTBI (LTBI-) through week 100. Two cases of active TB occurred in LTBI- patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI- patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI- patients.
No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long-term treatment with guselkumab was generally well-tolerated through up to 2 years in patients receiving LTBI medications.
接受肿瘤坏死因子（TNF）抑制剂治疗的患者有发生新发结核病（TB）或潜伏性结核感染（LTBI）再激活的风险。TB/LTBI与用于治疗银屑病的白细胞介素（IL）-23抑制剂之间的关联尚不清楚。LTBI患者通常在接受生物制剂治疗前开始进行LTBI治疗。
评估接受古塞库单抗（一种IL-23抑制剂）治疗的中度至重度银屑病合并LTBI患者的安全性以及LTBI治疗情况。
在VOYAGE 1和VOYAGE 2研究中，筛查LTBI的患者在基线时被随机分为接受古塞库单抗、安慰剂或阿达木单抗（一种TNF抑制剂）治疗。安慰剂→古塞库单抗的交叉治疗在第16周进行，阿达木单抗→古塞库单抗的交叉治疗在第52周（VOYAGE 1）或第28周及以后（VOYAGE 2）进行。使用汇总数据评估接受和未接受LTBI治疗的接受古塞库单抗治疗患者至第100周时活动性TB、不良事件（AE）、严重不良事件（SAE）以及明显异常的肝功能检查[丙氨酸氨基转移酶检测（ALT）；天冬氨酸氨基转移酶检测（AST）]的发生率。
在基线时，130例随机分组患者（古塞库单抗组：n = 69；阿达木单抗组：n = 36；安慰剂组：n = 25）LTBI检测呈阳性并接受了联合LTBI治疗（LTBI+）。在接受古塞库单抗治疗且无LTBI（LTBI-）的患者中，至第100周时未报告有活动性TB病例。接受阿达木单抗治疗的LTBI-患者中有2例发生活动性TB。至第16周时，在所有治疗组中，与LTBI-患者相比，LTBI+患者报告ALT和AST升高的比例更高。至第100周时，LTBI+和LTBI-患者中发生AE和SAE的患者比例相当。
接受古塞库单抗治疗长达2年的有或无LTBI患者均未报告有活动性TB病例，包括LTBI再激活。LTBI治疗在所有治疗组中均有效预防了LTBI的再激活。接受LTBI药物治疗的患者接受长达2年的古塞库单抗长期治疗总体耐受性良好。
