B14-04 Nintedanib Treatment in Children and Adolescents With Fibrosing Interstitial Lung Diseases (ILDs)

Rationale

In the placebo-controlled InPedILD trial, nintedanib had an acceptable safety and tolerability profile in children and adolescents with fibrosing ILDs. The open-label extension of the InPedILD trial, InPedILD-ON, assessed the longer-term safety and tolerability of nintedanib.

Methods

Patients who completed the InPedILD trial on treatment (nintedanib or placebo) were eligible to enter InPedILD-ON. Patients with a transition period between trials of ≤ 12 weeks entered InPedILD-ON as “rollover patients”. Patients from InPedILD with a transition period >12 weeks, and patients aged 6 to 17 years with a fibrosing ILD who had not participated in InPedILD, entered InPedILD-ON as “new patients”. In InPedILD-ON, all patients received open-label nintedanib. In the InPedILD trial, dosing of nintedanib was based on weight-dependent allometric scaling, with starting doses of 50, 75, 100, or 150 mg bid. Rollover patients received nintedanib at a dose corresponding to the dose of nintedanib or placebo that they received at the end of the InPedILD trial; new patients received nintedanib at a dose based on their weight, as in the InPedILD trial. Adverse events over the whole follow-up period of InPedILD-ON and changes from baseline of InPedILD-ON in FVC % predicted at weeks 52 and 104 were assessed descriptively.

Results

A total of 54 patients were treated with nintedanib in InPedILD-ON. At baseline of InPedILD-ON, mean (SD) age was 13.6 (3.3) years and mean (SD) FVC was 59.9 (20.9) % predicted. The most common diagnoses were surfactant protein deficiency (n = 13; 24.1%) and systemic sclerosis (n = 11; 20.4%). Median (minimum, maximum) exposure to nintedanib in InPedILD-ON was 103.7 (2.6, 156.9) weeks. Overall, 24 patients (44.4%) prematurely discontinued nintedanib (7 due to adverse events, 2 due to burden of trial procedures, 2 due to other treatment option available, 2 due to perceived lack of efficacy, 1 due to change of residence and 10 due to other/no reported reasons). The majority (66.7%) of patients who prematurely discontinued nintedanib did so after at least 52 weeks of treatment. The most frequent adverse event was diarrhea (Table). Adjusted mean (SE) changes in FVC % predicted from baseline to week 52 (n = 45) and from baseline to week 104 (n = 36) of InPedILD-ON were − 2.9 (1.4) and −1.9 (1.5), respectively.

Conclusions

The adverse event profile of nintedanib in InPedILD-ON was generally consistent with that seen in InPedILD, supporting the safety and tolerability of nintedanib in children and adolescents with fibrosing ILDs.

This abstract is funded by: The InPedILD and InPedILD-ON trials were supported by Boehringer Ingelheim.