A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma

Abstract

Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies.194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups. Secondary end-points included pre-bronchodilator lung function, rescue β2-agonist use and safety. Numerical end-points are reported as mean±sd.At week 13, change from baseline in ACQ-6 was -0.76±1.04 for tralokinumab versus -0.61±0.90 for placebo (p=0.375). Increases from baseline in forced expiratory volume in 1 s (FEV1) were 0.21±0.38 L versus 0.06±0.48 L (p=0.072), with a dose-response observed across the tralokinumab doses tested. β2-agonist use (puffs per day) was decreased for tralokinumab -0.68±1.45 versus placebo -0.10±1.49 (p=0.020). The increase in FEV1 following tralokinumab treatment remained evident 12 weeks after the final dose. Safety profile was acceptable with no serious adverse events related to tralokinumab.No improvement in ACQ-6 was observed, although tralokinumab treatment was associated with improved lung function.

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…Eosinophilic inflammation, for instance, is likely to have a Th2 immune component, a reflection of adaptive immunity, as evidenced by four separate studies demonstrating efficacy of a monoclonal antibody to IL-5 in eosinophilic severe asthma in adults [14,[56][57][58]. Whether the Th2 profile is similar to that observed in corticosteroid-naïve patients awaits further study, but would be supported by studies demonstrating efficacy of an anti-IL-13 antibody in improving FEV1 in adult patients with moderate-to-severe asthma [59,60]. Evidence for a Th2 pattern in severe asthmatic children remains controversial [61,62].…”

“…Another anti-IL-13 antibody, tralokinumab, did not improve symptoms but resulted in a non-significant increase in FEV1 when compared to placebo in all comers. Like lebrikizumab, it appeared to perform better in patients with detectable sputum IL-13 levels [60]. A study in moderate-to-severe asthma of a monoclonal antibody to the IL-4 receptor-a, that blocks both IL-4 and IL-13, was negative [160].…”

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

“…Приме-нение антагонистов IL13 лебрикизумаба и тралокину-маба при тяжелой бронхиальной астме в ряде исследо-ваний дало разочаровывающий результат. Отмечался лишь небольшой физиологический эффект, а симптомы и частота обострений сохранялись [34,35].…”

“…Выше мы отмечали разочаровывающие результа-ты применения лебрикизумаба (моноклональные анти-IL13 антитела) [34,35]. Дальнейшие исследования по-казали, что у пациентов с высоким сывороточным перио-стином по сравнению с больными, у которых его уровень был низким, применение лебрикизумаба сопровожда-лось выраженным улучшением функции легких (определя-ли ОФВ 1 ) [51].…”

Severe refractory asthma: an update

“…Antibodies against IL-13, lebrikizumab, showed improved pulmonary function testing but no effect on exacerbation rate or symptoms [94]. Another anti-IL-13 antibody, tralokinumab, showed improved pulmonary function without improvement of asthma symptom scores, although patients seemed to need less rescue medication [95]. In an unselected group of moderate-to-severe asthma patients the use of AMG 317, an anti-IL4 receptor blocker, showed no clinical benefit at all [96].…”