Asthma Allergies Children parent's web guide

Asthma Allergies Children | is a website devoted to ideas that are within the guidelines set by accredited medical authorities for treatment of asthma and allergies.

omalizumab

Monoclonal Antibodies—An allergist perspective on the new biologics

By

Interview with Dr. Purvi Parikh

Last week we published our latest piece on dupilumab (Dupixent). But this is just one of several biologic “miracle” drug that have found their way into the allergist formulary, starting with omalizumab, or Xolair. Our contributor Purvi Parikh, MD, took some time to answer some questions about this class of pharmaceuticals. —Henry Ehrlich

AAC: The new biologics all end in the letters mab, which stand for monoclonal antibodies. Can you explain to our readers what these are and how they are made?

Purvi: These are specialized antibodies that bind to different parts of the immune system. They usually work by blocking the functioning of that part, in effect “switching it off” or otherwise lessening its activity. Our body has naturally occurring antibodies that help us fight invaders such as infections, inflammation, autoimmune and cancer cells. These antibodies augment or supplant the natural ones that may be going wrong.

AAC: Can you explain how they work? Some of them work on IL-5, some on IL-13, for example. What does this mean?

Purvi: Different parts of the immune system are responsible for different kinds of protection.  These functions are important but sometimes can be detrimental when they are overactive such as in chronic diseases like asthma. Then you have a constant cycle of inflammation that can be dangerous for the body and its organs. IL-5 makes eosinophils, white blood cells that are important in fighting certain infections and parasites, but these are also one of  the white cells that drives asthma inflammation. They are drawn to inflamed tissue in the airways where they help prolong an asthma attack. As the term eosinophilic esophagitis (EoE) implies they can also cause trouble in the GI tract.

IL-13 is another inflammatory mediator.  It is secreted by Th2 cells, the t-helper cells that drive allergic and asthmatic inflammation, as opposed to Th1 cells that drive normal protection from things like colds.

Omalizumab, the original mab, works by binding an extra epitope to allergic IgE antibodies so they can’t attach themselves to mast cells properly, thwarting allergic reactions.

AAC: For 40 years or more the go-to medicine for asthma was inhaled corticosteroids, and I suppose still are. Of course they didn’t work for everyone. How do you decide whether it’s time to switch a patient to, say, Xolair–an anti-IgE drug– or mepolizumab (Nucala)–anti IL-5? Or benralizumab (Fasenra) or reslizumab (Cinqair) also popular IL 5 agonists?

Purvi: Usually we consider these drugs for those asthmatics who are uncontrolled despite their inhaled medications. What that means is despite their inhaled medications they are needing oral or injectable steroids – even one course in a whole year is deemed uncontrolled. Other signs of uncontrolled asthma are albuterol use more than 2x per week and nighttime symptoms including coughing, wheezing, chest tightness, and shortness of breath.

Being uncontrolled puts you at risk of heart disease and death, but it also makes day-to-day quality-of-life very difficult.

AAC: How many patients of yours have made the leap? And what are the results so far? Is it life changing for some?

Purvi: We have quite a few – close to 75 in our Allergy and Asthma Associates of Murray Hill office alone. The results are definitely life changing – they have reduced need for oral and Injectable steroids, unscheduled ER or office visits and hospitalizations. They may even have saved lives as we know ten people die per day in the US of uncontrolled asthma. They have also reduced the need for inhaled steroids. Also it is nice we can now personalize medicine and treat people based on what drives their asthma.

Moreover, by blocking allergic inflammation patients have benefited from better control of their nasal polyps, sinusitis, eczema and urticaria as well and reduced steroid need for these entities as well. Those different pathways aren’t specific to the lungs. And it’s very likely that an IL-13 drug, say, may affect 4, 5, or others.

AAC: I hate to be crass, but because these things are so amazingly expensive I have to ask: how much of a hurdle is the insurance system when you prescribe one of these things? Can you give our readers an idea of what you go through? The company that makes Dupixent, which treats atopic dermatitis but is being studied for asthma, created a hashtag #DeniedRX so that patients could Tweet about being turned down. Is it a struggle to serve your patients?

Dr. Purvi Parikh

Purvi: It is definitely a struggle and often insurance companies will make us jump through hoops by not only denying treatments but taking patients off of medicines like omalizumab that they have been stable on for years!  We are fighting but luckily a lot of the pharma companies are able to offer free drug and patient assistance for these denials so our patients don’t flare up and end up back in the hospital. Or worse..:

AAC: How do these drugs make their way to your practice? Do you hear about them in meetings? Read in journals? Reps? I went to a nice dinner in Bay Ridge a few years ago to hear about mepolizumab from a doctor from Yale–I was the only non-physician there so I guess that’s one format for education. And how do you decide to try them?

Purvi: Through a combination of those avenues – our last AAAAi meeting focused heavily on biologics and the studies supporting them so I found it helpful to learn, especially about the new ones. My training laid the foundation. Because my fellowship was comparatively recent, these meds were already part of the discussion–I am more comfortable using these meds compared to  the docs who trained before my time. Journals also are a great place to get evidence-based information. Industry reps are an excellent  resource in learning of new treatments and expanding patient access but it is important and our responsibility  as physicians to rely on the data from meetings, journals, and  colleagues rather than going all in on a sales pitch.

AAC: Thanks for your time as always.

Dr. Purvi Parikh is an adult and pediatric allergist and immunologist. She completed her fellowship training in allergy and immunology at Albert Einstein College of Medicine’s Montefiore medical center following her residency at the Cleveland Clinic and is board certified by the American Board Allergy and Immunology, as well as the American Board of Internal Medicine. She works with Dr. Ehrlich at Allergy & Asthma Associates of Murray Hill.

Diagram by GSK Source

 

 

Chronic Urticaria: the Omalizumab (Xolair) Difference

By

By Dr. Paul Ehrlich

Back when we wrote our book Asthma Allergies Children: a parent’s guide, Dr. Chiaramonte and I both expressed our exasperation over the dismal state of treatment for chronic urticaria—the fancy name for hives—by recalling our training. Larry remembered, “My teacher at Johns Hopkins said, ‘I’d rather have a tiger come into my office than a patient with chronic hives.’”

My version was from my fellowship at Walter Reed Army Hospital. We learned that 80 percent of the cases we would evaluate would never reveal a cause. My professor, Colonel Richard Evans, told us, “For those of you who are going into practice and will treat urticaria I would suggest having an office with two doors to the outside. You’ll need one door for your patient to enter and the other for you to sneak out.” His point was that many cases defy diagnosis, it often takes a while before the right treatment is determined, and patients are rarely satisfied with it.

That book was published in 2010 and it’s still very good—I give copies to my patients and young doctors who spend month-long rotations in the practice, although some bits need updating (that’s at least part of the mission of this website). I was particularly struck by this paragraph:

FUTURE TREATMENT?
A case recently came to our attention of a chronic asthmatic who had the good fortune (financially as well as medically, because the stuff costs $1,000 a month) to use Xolair. It helped not only with his asthma, but with his cold-induced urticaria. We can only speculate that this anti-IgE drug is functioning in the skin as well as the lungs. It makes sense to us, because cold can induce asthma in twitchy lungs. We doubt that this off-label use of Xolair will be transformed into an on-label use any time soon, not at current prices. p.110, 2010 edition

Here it is eight years later and we hardly use omalizumab for asthma in my practice but we use it for urticaria all the time. More important, we hardly hear from our patients in the intervals between their shots, where once we would have heard from the same patients all the time. Chronic urticaria like its cousin atopic dermatitis, or eczema, is a cause of active suffering day to day. Quality-of-life scores are much lower than for chronic diseases such as diabetes. Not only are the skin conditions intensely uncomfortable, they are disfiguring. Many years ago I had a 14-year-old girl patient who was hospitalized for suicidal depression because of her hives. It was a formative experience for me as an allergist.

A key milestone was a 2013 article in the New England Journal of Medicine that found dramatic improvements from omalizumab. There were the usual hurdles of further studies and insurance reimbursement along the way, but here we are in 2018 and omalizumab is pretty much standard of care. Genentech is also generous for those patients who struggle with the cost.

Omalizumab is so effective in treating hives that I find it bewildering to encounter physicians who still don’t use it. One prominent dermatologist I know still clings to the cycles of more steroids, topical and systemic, antihistamines, baths, and emollients. It should surprise me, but it doesn’t. In his book How Doctors Think, Dr. Jerome Groopman cites Douglas Watson, former president and CEO of Novartis (which helped develop omalizumab) to the effect that research shows that most physicians regularly prescribe around two dozen drugs, most of which they learned about during their training, although their training may have taken place many years earlier.

Along the way this anti-IgE drug has had its share of public relations and medical problems. There was alarm over a statistical association with cancer, although I am convinced it was just data noise. There are those who are allergic to the drug itself, complete with instances of anaphylaxis. That’s one advantage to giving shots in a clinical setting—the tools and the personnel are on hand to treat adverse events. The FDA has also raised concerns of risks to blood vessels supplying the brain and heart.

Regardless, my patients are happy with their Xolair–costs, inconvenience, and all because of the profound relief they have achieved. And if they’re happy, I’m happy. I even got rid of the back door to my consulting room.

(Note: we received no financial or other consideration from Genentech and Novartis for publishing this piece. It is based entirely on Dr. Ehrlich’s appreciation of a drug that has produced tremendous benefits for his patients.)

The High Cost of Treating Severe Asthma

By

Medical gold mine?
Medical gold mine?

By Dr. Paul Ehrlich

Great timing. An article on the front page of the Sunday New York Times on colonoscopies happened to coincide with the fact that I finally received an answer to a question eight weeks after I asked it. The Times piece was about colonoscopies and the part they play in our inflated national health care bill. Funny, I always thought doctors were looking for signs of cancer during this undignified procedure. It turns out they were also looking for gold.

A procedure that costs a few hundred bucks in other developed countries, runs anywhere from about $2800 in Cleveland, Milwaukee, and Salt Lake City to about $8500 in New York City. The gastroenterologist who’s responsible for actually looking for signs of disease actually makes less than the anesthesiologist who either administers general anesthesia—a largely unnecessary excess—propofol, which renders you unconscious just for the length of the scoping, or a bit of Valium. (Take note, music fans—propofol was the drug that allegedly did in Michael Jackson.) But don’t cry for the gastroenterologist. He may be a partner in the venue itself, which, like a hospital, can charge a whopping “facility fee.” These colonoscopy centers can provide a 100% return on investment in less than two years.

So, what does this have to do with allergies? One word: Xolair (or maybe two words, since the generic name for Xolair is omalizumab). Allergists use Xolair, also known as the anti-IgE antibody, to treat very severe cases of asthma. Xolair must be injected slowly, it is often painful for patients, has side effects and therefore requires observation, and is also incredibly expensive—upwards of $1200 per shot. After my staff gets through with the elaborate coding, arguing with insurance companies, and so forth, I end up giving it practically at cost.

With this in mind, when I was approached by hospitals I am affiliated with to take my Xolair patients for their injections, it made sense. They would assume the entire paperwork burden and I wouldn’t lose space in my waiting room for observation, or indeed my own precious capacity for paying attention to patients who are receiving a powerful drug. But then I asked the question, “What do you charge to give one of these shots?” Eight weeks later, I got the answer: $5500.

I’m not doing it. Certainly the red tape is extraordinary. But these are my patients, and I don’t want to lose the continuity of treatment and observation while they report to another facility even if I don’t get paid. Would I like to split the difference between what I charge and what the hospital charges? Sure. And if the insurance companies had any sense they would find a happy median. I even know where they can find the money–they can just make up the additional payments to me out of their savings in other medications and emergency treatment. Regardless, no more referrals from me.

Xolair Roundtable: Three US doctors react to UK restrictions

By

A few months ago, we noticed news from England that Britain’s national health service (NHS) rejected use of Xolair for after the National Institute for Clinical Excellence (NICE) said it was too expensive. NICE also said that Xolair, known generically as omalizumab, provided “little additional benefit over existing drugs for the treatment of severe persistent allergic asthma in most children aged 6-11”.

We decided to send the news for comment to Dr. Janet Sullivan, chief medical officer for Hudson Health Plan, New York State’s top-rated health plan for Medicaid and Child Health Plus, since it seemed to be the most directly comparable to the UK’s NHS of any payer we know. We also showed it to our own panel of experts—Dr. Chiaramonte and Dr. Ehrlich. Their comments follow Dr. Sullivan’s.
—Editor, AsthmaAllergiesChildren.com

We do cover Xolair, but we require prior approval. The drug is VERY expensive, and we want to be sure it is used appropriately. I recently approved a case that we had sent out to an allergist for review. The reviewer recommended we NOT approve Xolair because the child’s IgE levels were higher than those for which the drug was tested, and was therefore “off-label.” Because the child had significant morbidity from asthma, I discussed the case with the referring allergist and we agreed on a few months’ trial.

I am not familiar with the studies that were reviewed by NICE but their criteria for effectiveness are stronger than ours. The pharmaceutical lobby in the United States is so powerful that new drugs are not required to demonstrate benefit in comparison to existing treatments and the cost of a treatment is not considered in the FDA approval process. A new drug can be FDA approved even if it is less effective than an existing treatment and costs ten times more. In my opinion, this policy benefits drug companies more than it benefits patients.

On the other hand, limitations on the clinical setting for which a drug is approved can be arbitrary. When a drug is approved for a certain age range, or IgE level, it is because those were the conditions that were tested. It doesn’t necessarily mean that the drug is unsafe or ineffective for people in a different age range; it just hasn’t been tested.

When appropriately used, a very expensive drug like Xolair can be both a good medical and economic choice if it improves the patient’s quality of life and prevents repeated ER visits and hospital admissions. That is why we review each case.

Dr. Janet Sullivan–Chief Medical Officer, Hudson Health Plan, Tarrytown, NY

Xolair is not approved by the FDA for use in children less than 13 years of age. Successful multi-center clinical trials are required before the FDA will grant approval. Because of its cost [approximately $1,000/per treatment], Xolair is limited to severe persistent asthmatics who have required systemic steroids in adults. This would be the case if approval is obtained for children.
I analyzed twenty adult patients who met the criteria for Xolair, using the standardized Asthma Control Test [ACT.} An ACT score of a completely well patient is between 20-25 points; below 20 points indicates asthma of increasing severity as the score lessens. The twenty patients studied had scores between 8-10 points. The ten asthmatics who did not get Xolair because they lacked HMO approval remained at their original ACT scores. The ten who received Xolair had ACT scores of 18-20 points within four months of treatment. If Xolair is used in children improvement is expected to follow the adult pattern of occurrence within four months.

Dr. Larry Chiaramonte

I find the NHS decision absolutely ridiculous. The studies which already have been done in the US in children six to eleven have shown Xolair to be not only effective but also money saving. The severe asthmatics might end up costing between $5,000 and $10,000 per visit in hospitalization thus approaching one-year cost of Xolair. This doesn’t even include the cost of medication on an outpatient basis. I look forward to FDA approval, which should be in about 12 months. I follow UK medical choices because I worked at a prestigious London hospital for a time many years ago and still have friends who practice there. Based on that experience and interest, I know a UK political story when I see one.

Dr. Paul Ehrlich

SiteLock
%d bloggers like this: