麻豆传媒

DALLAS – Doctors are more frequently switching biologic agents in patients with severe asthma who have been unable to control or tolerate treatment with their initial therapy, a researcher said at the annual meeting of the American Thoracic Society here.

In a case review, there were 29 situations where doctors took a patient off one biologic – most frequently omalizumab (Xolair) -- and replaced that medication with another, generally one that targeted interleukins, reported Lauren Eggert, MD, of Stanford University School of Medicine in California.

"We found that doctors are becoming much more comfortable switching between the different biologics, and giving them a 3 to 6 month trial period," she told 麻豆传媒. "If they are started on omalizumab and there is no systemic response, or no decrease in exacerbations or improvement in lung function, the doctors are feeling very comfortable in switching to another biologic of a different class, assuming they still believe there is still a TH2 inflammatory phenotype."

In Eggert's poster presentation, 26 patients diagnosed with severe asthma had been taking omalizumab before they were switched to other agents. Two patients on omalizumab monotherapy added mepolizumab (Nucala) in a combination regimen. One patient first tried omalizumab and then tried 3 other biologics -- mepolizumab, reslizumab (Cinqair), and then benralizumab (Fasenra).

Eggert said that after the switches, 20 patients were being treated with mepolizumab, 4 were on benralizumab, 2 were on dupilumab (Dupixent), 2 were on omalizumab, and 1 was on reslizumab in combination with omalizumab.

"This is a work in progress," she said. "The most common thing [...] is that patients are being switched from omalizumab, an anti-IgE agent, to one of the newer biologics. Omalizumab is one of the older drugs, being approved by the FDA in 2003 and is one of the most common biologics that these patients are on. They are often given omalizumab as the first biologic. The newer 4 biologics that have been approved work against Interleukin 4, IL-5, and IL-13."

"It appears that these switches can be done safely and effectively," Eggert said. "Doctors are even now trying to combine biologics, generally omalizumab with its anti-IgE activity and then one of the interleukin inhibitors."

She said that the 2 cases in her chart review that involved combination therapy had mixed results. "One of those patients improved on the combination and was able to taper the use of prednisone. The other patients did not improve on the dual therapy," Eggert noted.

Eggert said that combination therapy might be the only option for patients whose asthma is not controlled. "When you are getting to the point where you need 2 biologics because you are in the hospital every month because of severe asthma, you start trying a lot of different things," she said.

In commenting on the study, David Halpin, MBBS, DPhil, of the University of Exeter in England, told 麻豆传媒, "Amongst people treated with biologics, there are some that respond, [and] there are some that develop other features that make you want to consider switching to other medications. Sometimes they can't tolerate it."

"What we don't have is a good hierarchy of which order we should try biologics or predictors of which ones will have a lack of response or predictors of those who will be more likely to respond, and this paper hasn't found those predictors either," he added.

Eggert said one of the goals of her study was to try to identify from baseline data biomarkers that would predict which patients would do better on any of the biologics, but the research team was unable to find a predictive clue in the work at this point.

She also found that some providers are comfortable using the anti-asthma biologics with other biologics in other fields, such as with adalimumab (Humira). "So far, the records do not show any adverse events in these combinations," Eggert said.

"I think this situation of combining biologics is an evolving field, especially in patients with high TH2 asthma. It makes sense to target different parts of the pathway," she said. "One of the future directions we will take with this research is to try to identify patients who might best benefit from a combination approach and assess safety with combination biologics."

She said there appears to be a trend of doctors moving away from omalizumab as a first choice of a biologic. Instead, they are moving toward prescribing mepolizumab as a first line therapy in these severe asthma patients who are not controlled on other medications.

"The idea of combining treatments is intriguing," Halpin said. "In rheumatology, they combine therapies and in gastroenterology they do as well, so there may be a benefit to that but we don't have the evidence of that at this time in asthma. These are expensive drugs as well so we have to be careful about making these regimens too costly for the patients."

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