"Biologics are wonderful for treating a specific patient," says Carol Smith, MD with Birmingham Allergy & Asthma Specialists. "Typically there is a group of patients who doesn't respond to the usual treatment. That group, with severe refractory allergy, is who the biologics are for."

This subgroup covers about five percent of asthma patients who may regularly take high-dose inhaled corticosteroids to fight the inflammation in their airways which may not work effectively. In addition, the steroids can create devastating side effects from their long-term use, such as glaucoma and bone fractures.

Biologics, however, relieve respiratory inflammation differently without stimulating the harmful side effects. These relatively new types of drugs target a single biomarker of the condition, such as a certain type of cell.

In the last three of the four severe asthma biologics on the market, that biomarker is eosinophils. These specific white blood cells typically manifest in high numbers in about half of patients with severe asthma.

The biologics each block a different subunit of the interleukin-5 receptor on the eosinophil surface. Unable to access this major cytokine, the eosinophil cannot proliferate and even die. "They all work by decreasing the effect of eosinophils on airway inflammation," Smith says. "And they work really well."

Nucala (mepolizumab) was the first interleukin-5 antagonist monoclonal antibody to target eosinophil levels. By the time of its FDA approval in late 2015, it had been found to reduce eosinophils by approximately 80 percent within four weeks.

A few months later, Cinqair (reslizumab) received its FDA approval. Patients receiving reslizumab showed a 92 percent reduction in mean eosinophil counts by week 52.

Both drugs are administered every four weeks by injection or intravenous infusion at a physician's office while patients continue to take their normal asthma medications to maintain adequate control of the disease.

The latest asthma biologic, Fasenra (benralizumab), hit the market last November. "Benralizumab is also a monoclonal antibody against the IL-5 receptor, but this is against the alpha subunit of the receptor, so it's a bit different," Smith says. It also extends the dosing schedule to every eight weeks. Fasenra has shown up to a 51 percent reduction in asthma exacerbations and a 75 percent reduction in daily oral steroid use.

The notable downside to biologics is the cost. "They're very expensive--$600 to $1,500 per vial. And a patient sometimes needs more than one per month," Smith says. Most of the time, insurance will cover the cost or the drug company will endeavor to work out some sort of assistance.

"The justification for purchasing the high-cost drugs is that the biologics keep people out of the hospital, so they reduce their healthcare costs," Smith says. Currently, the approximately five percent of patients with severe refractory asthma account for approximately half of the expenditures on asthma in the U.S.

But getting approval can still be difficult. "It's time consuming for the offices to do all the paperwork," Smith says. "And it might get denied several times before the payor finally says OK."

Interestingly, these biologics may be helpful to a broader band of severe asthma sufferers. Allergists have noted that a person does not need dramatically elevated eosinophils to reap a benefit. Even people within the normal 150 range can see an improvement. Although clinicians learned in trials while developing the biologics that the higher the eosinophil count, the better the response.

That knowledge could encourage allergists to randomly check the eosinophil count in every severe allergy patient to see if they might benefit from biologic therapy.

Though the three biologics may all target eosinophils, because they do so in a different manner means their impact on each patient may differ. "One biologic won't work for everybody," Smith says. "You have to look at their endotype, something about that patient that you can target."

"But for physicians treating people with severe asthma, the message of biologics is to keep in mind that there are more than just steroids to treat these patients," Smith says. "If a patient is having to use steroids more than once or twice a year, and all their comorbid issues, such as smoking and acid reflux, have been dealt with, it might be time to refer them to someone who can evaluate them to see if a biologic might be beneficial."