Encouraging results of nintedanib in children with fibrosing ILD 

With an acceptable safety profile and promising efficacy data, nintedanib is a potential candidate for treating children and adolescents with fibrosing interstitial lung disease (ILD).

There is a clear medical need to find treatment options for childhood ILD. Nintedanib could be a potential candidate due to its shown benefits in adults with fibrosing ILD and the existing similarities in the pathophysiology of fibrotic lung remodelling in adults and children [1,2]. To investigate nintedanib in children, Dr Robin Deterding (Children’s Hospital Colorado, CO, USA) and colleagues designed the phase 3 InPedILD trial (NCT04093024) [3,4].

Patients aged 6–17 with fibrosing ILD (n=39) were randomised 2:1 to nintedanib or placebo in the 24-week, double-blind period. Hereafter, all participants received nintedanib in the open-label phase of the trial. Nintedanib dose was based on weight, ranging from 50 mg, twice daily, for patients between 13.5 and 23 kg, to 150 mg, twice daily, for patients ≥57.5 kg. The co-primary endpoints were area under plasma concentration-time curve at steady state and treatment-emergent adverse events after 24 weeks of therapy.

The exposure achieved with weight-based dosing was within the range observed in adults who were treated with nintedanib 150 mg, twice daily. Regarding safety, 84.6% of the participants experienced at least 1 adverse event, irrespective of treatment arm. As expected by the authors, diarrhoea was the most common adverse event in the nintedanib arm (38.5%). In the control arm, only 15.4% of the patients experienced diarrhoea. Other frequently reported adverse events were vomiting, dental caries, nausea, and abdominal pain, with comparable rates for the 2 study arms.

Although the study was not powered to assess efficacy, the trends favoured the experimental arm: adjusted mean change in forced vital capacity (FVC) predicted at week 24 was 0.3% for nintedanib versus -0.9% for placebo; adjusted mean change in peripheral capillary oxygen saturation (SpO₂) at rest after 24 weeks of therapy was 0.07% for nintedanib versus -2.25% for placebo.

“These data support a positive benefit-risk assessment for the use of nintedanib in children and adolescents with fibrosing ILD,” concluded Dr Deterding.

1. Glasser SW, et al. Pediatr Allergy Immunol Pulmonol. 2010;23:9–14
2. Richeldi L, et al. N Engl J Med. 2014;370:2071–2082.
3. Deterding R, et al. Nintedanib in children and adolescents with fibrosing interstitial lung disease: the InPedILD ERS International Congress 2022, Barcelona, Spain, 4–6 September.
4. Deterding R, et al. Eur Respir J. 30 Aug, 2022. Doi:10.1183/13993003.01512-2022.

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Posted on 30 October 202217 May 2024