Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.
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DALLAS, Texas – While most people with asthma can be treated with a variety of drugs, about 10 percent of the 337 million people in the world go on to develop severe asthma, and for that group new biologic agents appear to only way to keep the disease in check.
At the annual meeting of the American Thoracic Society here, researchers in France and elsewhere investigator how well those drug work in the real works – as compared to how they worked in clinical trials that led to their approval.
In a retrospective study, Camille Taille, MD, PhD, professor of pulmonology at Hospital Bichat, Paris, and her colleagues checked the effectiveness of the newest anti-asthma drug on the block, dupilumab (Dupixent) and reported that the 64 patients treated with the drug under a compassionate use protocol reduced the number of asthma exacerbations from an average of 4 in the previous year to 1 while taking dupilumab, a statistically significant reduction (P<0.001).
She said that the treatment effect on exacerbations was across the board. Forty of her patients – 78.4 percent of the total — lowered their exacerbation rate by more than 50 percent. She said that in the previous 12 months, patients in the study had required 28 hospitalizations due to their severe asthma, and that was reduced to 7 hospitalizations in the year on dupilumab.
“These patients had severe airway obstruction, high exacerbation rates, were frequently-steroid dependent and had severe steroid side effects,” Dr. Taille said. “A vast majority of these patients failed to respond to previous therapies.” She noted that many of her patients responded to treatment even though patients with such severe disease were not included in the randomized clinical trials.
Dr. Taille said that the patients FEV1 (forced expiratory volume in 1 second) improved from 51 percent of predicted volume to 66.5 percent after one year of treatment (P<0.001). And FEV1 was increased from 1410 mL to 1860 mL after a year (P>0.001).
The need for the use of oral corticosteroids was also reduced among patients on dupilumab. The average patient was taking 20 mg of prednisone a day in the 12 months before getting on dupilumab, and while on the drug, the steroid dose was reduced to a mean of 6 mg a day (P<0.001). She said 13 of the 64 patients were weaned off of steroids and 28 patients had their steroids reduced by at least 50 percent.
“This is the first real life evaluation of dupilumab in severe asthma patients,” Dr. Taille said. In her study, the patients were about 51 years old; 53 percent were female; 50 percent of the patients were either current or former smokers; 61 percent were diagnosed with allergies; 53 percent were diagnosed with gastroesophageal reflux disease.
“These data from a retrospective study in a real-life environment corroborate the efficacy of dupilumab treatment for patients with severe asthma,” she said.
Although the French study was a year in length, Prerna Sharma, a resident in pulmonary medicine at the University of Pittsburgh Medical Center, in Pennsylvania said her 5-month study that included treatment with mepolizumab (Nucala) and reslizumab (Cinqair), both relatively new drugs on the market for treating severe asthma, showed virtually the same findings.
“This real world analysis shows a generally positive response to mepolizumab and reslizumab in patients diagnosed with severe eosinophilic asthma,” she said. Overall, 80.8 percent of the 125 patients in her study showed a reduction in their exacerbation rate when compared to the time before being treated with one of the newer agents.
In her poster presentation, Dr. Sharma said the difference in FEV1 in her patients trended towards significance with patients improving from 1.9 liters to 2.0 liters after 5 months (P=0.072).
The reduction she saw in steroid was significant as the dose was reduced from a mean baseline use of 11.7 mg at to 8.9 mg at 5 months (P=0.002).
Exacerbations were reduced from an average of 4.7 attacks to an average of 1.5 attacks (P<0.001).
In the study, 82 of the patients were being treated with mepolizumab, while another 32 patients had been switched from mepolizumab to reslizumab. There were 11 patients who were only treated with reslizumab. Their average age was 57; 65.6 percent of the population was female; 83 percent had been identified with adult onset disease.
And what happens when the new biologics fail. Try another one, another group of researchers suggested.
Lauren Eggert, MD, a pulmonary critical care fellow at Stanford University School of Medicine in California, said that patients with severe asthma who have been unable to control or tolerate treatment with one biologic agent – most frequently omalizumab (Xolair) – are usually switched to another biologic.
In reviewing cases of severe asthma, said she had identified 29 situations in which doctors took a patient off one biologic and replaced that medication with another. “We found that doctors are becoming much more comfortable switching between the different biologics, and giving them a 3 to 6-month trial period,” Dr. Eggert said. “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 her study, 26 patients diagnosed with severe asthma had been taking omalizumab before they were switched to anther agents. Two patients on omalizumab monotherapy added mepolizumab in a combination therapy. One patient first tired omalizumab and then tried 3 other biologics — mepolizumab, reslizumab and then benralizumab (Fasenra).
She said that after the switches 20 patients were being treated with mepolizumab, 4 were on benralizumab, 2 were on dupilumab, 2 are on omalizumab and 1 is on reslizumab in combination with omalizumab, she reported.
“This is a work in progress,” Dr. Eggert said. “What I found is the most common thing that is being done 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,” Dr. Eggert said. “Doctors are even now trying to combine biologics, generally omalizumab with its anti-IgE activity and 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 in the combination and was able to taper the use of prednisone,” she said. “The other patients did not improve on the dual therapy.”
She 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 medications because you are in the hospital every month because of severe asthma you start trying a lot of different things,” she said.
Dr. Eggert also found that some providers are comfortable using the antiasthma biologics with other biologics in other field such as with adalimumab (Humira). “So far the records to do not show any adverse events in these combinations,” she 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.”