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?
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