Kate Johnson

November 13, 2013

BALTIMORE — Self-administered treatment for angioedema seems to be gaining popularity with clinicians and patients, according to an international survey sponsored by CSL Behring.

This form of treatment is the way of the future for hereditary angioedema, said lead investigator Timothy Craig, DO, from Penn State University in Hershey, Pennsylvania.

"For all of these drugs, if you can eliminate the infusion room or emergency department, you can lower the cost," he told Medscape Medical News. When the infusion room or emergency department is factored in, the cost of treatment can be 3.6 times the price of the drug.

Another benefit of self-administration, "at least in the acute setting, is that the earlier you treat, the better response, the less absenteeism, the less loss of productivity," Dr. Craig explained.

Results, implications, and recommendations arising from the online survey were discussed during an industry-sponsored meeting of experts in hereditary angioedema here at the American College of Allergy, Asthma & Immunology (ACAAI) 2013. The meeting was headed by Dr. Craig, who is lead author of the World Allergy Association's recent guidelines, which recommend self-treatment for hereditary angioedema (World Allergy Organ J. 2012;5:182-199).

A 16-question online survey on self-treatment for hereditary angioedema was sent to 21 centers in Canada, Europe, and the United States. Ten centers completed the survey — 1 from Canada, 8 from Europe, and 1 from the United States.

For all of these drugs, if you can eliminate the infusion room or emergency department, you can lower the cost.

The majority of centers (n = 7) reported that at least half of their patients now self-administer therapy, whether for the acute treatment of an attack or for prophylaxis. More patients were self-administering in the United States than in Europe or Canada (75% vs 47% vs 10%).

The most widely used treatments were icatibant (Firazyr, Shire), which is the only therapy approved by the US Food and Drug Administration (FDA) for subcutaneous self-administration, and a plasma-derived C1-esterase inhibitor concentrate (Berinert, CSL Behring), which is approved for intravenous (IV) self-infusion.

Overall, 49% of patients were using icatibant and 47% were using the C1-esterase inhibitor.

An IV self-infusion C1-esterase inhibitor concentrate (Cinryze, ViroPharma) used for prophylaxis, not acute treatment, was not available in some countries at the time of the survey. Only 4% of patients were self-administering that agent.

The 3 main requirements for self-administration identified in the survey were patient motivation, mental ability, and clinical need. Barriers to self-administration were patient skill, mental capacity, and the need for nursing resources to provide training.

Centers in Canada and Europe indicated that they provide self-administration training, but in the United States, training is offered by a home-nursing agency.

"In Europe, they don't have health agencies that go to homes or specialty pharmacies to offer training, so they have to teach patients themselves. That's a major barrier," Dr. Craig explained. "Fortunately, we don't have that in the United States. IV self-administration, in particular, is not something you teach a patient in one sitting; you have to make sure they have expertise, so you have to do it a few times. Subcutaneous administration, though, I can teach in one sitting."

The expert panel suggested additional nursing or training resources as a solution, and a 24-hour hotline was proposed as a way to overcome some of these issues.

Some experts were concerned about the ability of a patient to recognize an attack and remember infusion techniques, especially in cases where attacks are infrequent.

Dr. Craig explained that there is a learning curve, not just for patients, but also for allergists. In fact, IV-self administration is not unusual. "In the hemophiliac community, they teach kids at a very early age to self-infuse. It's just that it's unusual for allergists."

Training Techniques

The panel suggested that individual disease management and attack plans for patients could help, along with the establishment of national centers of excellence to standardize training and establish best-practice techniques.

Asked about the low rate of self-administration in Canada, Paul Keith, MD, one of the panel members from McMaster University in Hamilton, Ontario, said the timing of the survey — June 2012 — had a big influence on the reporting of self-administration and specific medications.

"Many patients in the United States are trained to self-administer icatibant, but that is not readily available in Canada," he told Medscape Medical News. And although the CI-esterase inhibitor concentrate Berinert was approved by the FDA in 2009, it was not approved in Canada until September 2011.

"When this survey was conducted, we lacked the nursing resources to train patients, and Berinert had only recently been approved. However, since then, I am happy to report that we have trained about 50% of our patients in IV self-infusion," he said.

It is disappointing to see the low number of survey respondents, said Richard Gower, past president of the ACAAI and hereditary angioedema specialist in private practice in Spokane, Washington, who was asked to comment on the survey. However, "it starts the process of documenting the value of self-administration, and that's important," he told Medscape Medical News.

After years of little to offer patients with hereditary angioedema, things are suddenly moving very fast, which is both exciting and perhaps bewildering to some clinicians in this field, he said.

Fast-Paced Change

"This is my 37th year of practice. I've spent all but the last 6 years of my career with nothing but attenuated androgens and fresh frozen plasma to offer patients. I am so excited with all the options we have now," Dr. Gower said. "The beautiful thing is that we now have several different drugs that are mechanistically different. The dilemma is which patient should have which one."

Amid the excitement, it is worth considering that there could be some downsides to the movement toward self-treatment, such as the potential overuse of medication "by people who have a low tolerance for any discomfort," he noted.

"The guidelines all say that any attack should be eligible for treatment, preferably at home. I don't disagree with that, but should every attack be treated? You could make a case that every attack in the little finger or toe could, in 10 minutes, be in the throat, which is true; you do not know how it's going to progress. But a number of these patients have had this for 10, 20, 30, even 50 years with no treatment, and they sort of know themselves," he said.

The overuse of acute medications for hereditary angioedema poses virtually no medical risk to patients, but the huge costs could be a problem.

"I think the people who make the decisions about when to treat should be the patient and their families first, and then the physician or provider next. In this era of increasing cost-consciousness and regulation, if that gets out of hand, it could bring more regulations," he said.

Another potential downside could be lack of data collection.

"Because of the great success of these medications for acute treatment at home, there seems to be a loss of monitoring and capturing of data. Patients do not report attacks and they do not come in to see their physicians; that's a problem," Dr. Gower explained. "The more we know, the more we can find out."

"This also risks new restrictions from insurance companies who might say that patients don't qualify for prophylaxis because their attacks are so infrequent, when they are actually frequent but just not recorded in the chart," he said.

The survey was sponsored by CSL Behring, which markets Berinert. Dr. Craig reports financial relationships with CSL Behring, Dyax, Genentech, GlaxoSmithKline, Merck, Novartis, Pharming, Shire, and ViroPharma. Dr. Gower reports financial relationships with Bausch & Lomb, CSL Behring, Boehringer Ingelheim, Circassia, Eli Lilly, Dyax, GlaxoSmithKline, Genentech, HollisterStier, Mylan Specialty, Novartis, Roche, Sanofi, Shire, Teva, and ViroPharma.

American College of Allergy, Asthma & Immunology (ACAAI) 2013 Annual Scientific Meeting: Abstract P88. Presented November 9, 2013.


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