Tiotropium Showing Promise in Pediatric Asthma

Medscape Medical News from:

• CHEST 2014: American College of Chest Physicians Meeting

JIM KLING
October 31st 2014

AUSTIN — In children with poorly controlled asthma, once-daily tiotropium delivered with the Respimat inhaler improves lung function when added to inhaled corticosteroids, with no apparent change in adverse effects, new research has shown.

The drug and device combination is approved for the treatment of chronic obstructive pulmonary disease (COPD), and the manufacturer, Boehringer Ingelheim, is exploring US Food and Drug Administration approval for asthma.

Anticholinergic medications have long been used to treat acute asthma attacks, but recent evidence suggests that they could be useful as maintenance therapy in refractory patients.

"That got Boehringer Ingelheim interested in looking at the asthma part of this, not just COPD," said Mark Vandewalker, MD, principal investigator for clinical research at The Ozarks in Columbia, Missouri. He presented the research here at CHEST 2014.

In adults with asthma, the combination is an effective add-on to inhaled corticosteroids (N Engl J Med. 2012;367:1198-1207), so this study looked specifically at a pediatric population.

The 48-week phase 3 trial involved adolescents who had asthma for at least 3 months, a forced expiratory volume in 1 second (FEV₁) predicted of 60% to 90%, and a score of at least 1.5 on the Asthma Control Questionnaire 6-point scale.

The age range was 12 to 17 years, 65% of the cohort was male, mean asthma duration was 7.86 years, and mean baseline FEV₁% predicted was 82.8.

Participants had not smoked in the previous year or had never smoked. They were randomized to receive once-daily tiotropium, either 5 μg or 2.5 μg, or placebo, all delivered with the Respimat inhaler. The drug was given as an add-on to inhaled corticosteroids, in doses of budesonide 200 to 400 µg or equivalent for 12- to 14-years-olds and 400 to 800 µg for 14- to 17-years-olds.

The primary end point was peak FEV₁ in the 3 hours after dosing at week 24. The secondary end point was trough (predose) FEV₁ at week 24, which was measured 10 minutes before receiving that day's dose. FEV₁ peak in the 3 hours after the dosing and trough responses were also measured at week 48.

Table 1. Peak FEV₁ for Tiotropium Compared With Placebo

Variable	Adjusted Mean Difference (mL)	P Value
Tiotropium 5 μg
Week 24 FEV₁ area under the curve	174	.0005
Week 48 FEV₁ 3 hours after dosing	174	.0006
Tiotropium 2.5 μg
Week 24 FEV₁ area under the curve	134	.0085
Week 48 FEV₁ 3 hours after dosing	176	.0007

able 2. Trough FEV₁ for Tiotropium Compared With Placebo

Trough FEV₁	Adjusted Mean Difference (mL)	P Value
Tiotropium 5 μg
Week 24	117	.0320
Week 48	157	.0044
Tiotropium 2.5 μg
Week 24	—	ns
Week 48	137	.0154

The adverse-event profile was similar in all three groups, except there were some differences in drug-related adverse events and headache.

"You might think dry mouth would be a concern, and so far it hasn't been," said Dr Vandewalker. "My thought is that that's due to the Respimat device. We do see dry mouth with the older HandiHaler device."

Table 3. Incidence of Adverse Events

Adverse Events	Tiotropium 5 μg (n = 134), %	Tiotropium 2.5 μg (n = 125), %	Placebo (n = 138), %
One or more	62.7	63.2	59.4
Severe	1.5	1.6	2.2
Drug-related	3.0	0.8	0.7
Headache	6.7	5.6	1.4

For children whose asthma is not under control, the drug could be a useful option. "It looks like it was a beneficial treatment. So far, the teenagers are responding in a manner similar to adults — in fact more robustly — which we kind of expect because they haven't had asthma quite as long, so have less damage to their airways. The safety profile has been as good as, if not better than, that seen in adults," Dr Vandewalker added.

The drug would be a welcome addition to pediatric asthma care, according to Chris Carroll, MD, from the University of Connecticut in Hartford, who attended the poster presentation.

"For children with refractory asthma who are on moderate steroids and not well controlled, it would be really nice to have other options. It's great that they're doing pediatric studies because for a lot of medications, they don't bother," he told Medscape Medical News.

He said he finds the data reassuring. "I don't have any specific concerns about safety for this medication," Dr Carroll said.

This study was funded by Boehringer Ingelheim. Dr Vandewalker has received research report from the company. Dr Carroll disclosed no relevant financial relationships.

CHEST 2014: American College of Chest Physicians Meeting: Abstract 1994584. Presented October 29, 2014.