People with asthma are likely to benefit from combining medications to manage their symptoms, a strategy that requires doctors and patients to work together to tweak prescriptions, Dutch researchers say.

Based on a review of data from 64 asthma drug trials, the new study found that patients using inhaled corticosteroids with a long-acting bronchodilator had about half as many symptom flare ups and asthma attacks as those just on the steroids.

“There were some things we expected beforehand, like that oral therapies would be inferior to inhaled steroids, but asthma is a very individual disease and some patients will not experience any symptoms and other patients will suffer a lot from the symptoms,” said lead author Dr. Rik Loijmans, from the Academic Medical Center at the University of Amsterdam.

Although the worst breathing problems associated with asthma usually occur in episodes or “attacks,” the problem of a sensitive, swelling airway is constant. Treating asthma means being able to take medication that works quickly to relieve an attack as well as one that will keep the swelling under control, he told Reuters Health.

Worldwide, approximately 300 million people have been diagnosed with asthma, according to the Global Initiative on Asthma (GINA). That number is expected to rise to 400 million by 2025.

Asthma rates in North America are among the highest in the world, according to GINA, with some 36 million cases in the U.S. and Canada, representing more than 11 percent of the total population.

While corticosteroids can keep airways from swelling and building up with mucus, long-acting beta antagonists (LABAs) keep the muscles of the airways relaxed, resulting in fewer asthma attacks.

Normally, when patients are diagnosed with asthma, they are first treated with low-dose inhaled corticosteroids, and if there is reason to step up the therapy, such as recurring attacks, then the dose would likely be raised. Adding more drugs to the treatment regimen would come later.

Some products combine steroids with LABAS in a single treatment, such as GlaxoSmithKine’s Advair and AstraZeneca’s Symbicort. But in the U.S., those products carry a “black box” warning, which discourages their being used widely, researchers said.

To compare the effectiveness of all available asthma management strategies, Loijmans and his colleagues sifted through data from drug trials and selected the ones that met their criteria for making the results comparable. For instance, trials had to last 24 weeks or more, all patients had to have moderate to severe asthma, to have used a “rescue drug” to stave off an attack, or to have experienced nighttime waking because of an asthma episode.

“It scares me a bit to think that there is such an ailment that so many people suffer from and receive years of treatment for yet there are only 64 trials with duration of more than 24 weeks published,” Loijmans said.

The researchers compared 15 different drug management combinations to one another, and to treatment just with a low dose of the anti-inflammatory corticosteroids.

The trials included drugs that prevent swelling, as well as drugs that block immune system chemicals that can trigger attacks and those classified as rescue or “reliever” drugs, to be used specifically in the case of an asthma attack. The study team gauged the safety of medications by counting how many people dropped out of a trial

“A side effect in the trial that results in dropping out means that that person would have had a bad reaction to the medication if they had tried it outside of a study and that means it wasn’t very effective in helping that patient,” Loijmans said.

Overall, the combination of inhaled corticosteroids with LABAs – either as two separate drugs, or in a fixed dose delivered together - were the most effective at reducing the number of attacks patients experienced, according to the results published in the British medical journal BMJ.

Combinations of other drug types were not better than corticosteroids alone, and no single drug was better than steroids alone either.

The combination regimen also proved safe, according to the study results, including the products that combine two drugs into one treatment.

“Yet, these are the products with black box warnings,” noted Dr. Ken Chapman, director of the Asthma and Airway Centre of the University Health Network in Ontario, Canada.

The U.S. Food and Drug Administration (FDA) required the black box label because the combination products were associated with an increased risk of wheezing, which can lead to an asthma attack, according to Chapman.

That makes patients leery of the products and doctors hesitant to prescribe them, he said.

Chapman told Reuters Health that the Dutch researchers’ analysis and conclusions are not surprising, in fact, they are very well known, but the review is the most rigorous presentation of the data he has ever seen.

“It’s interesting that the FDA is willing to ignore this knowledge but there is a reason the drugs are still on the market. The world knows that this combination is effective,” Chapman said.