• Claire N. Saunders

Overeducated & Overmedicated: My Experience with Asthma Biologics

Updated: Mar 25

#asthma #biologics #medications #medicine #healthcare #pulmonary #immune #health #wellness #research #churgstrauss #egpa #eczema #psoriasis #chronicillness #stayinghealthy #immunology #rheumatology #immune #autoimmune #eosinophils #eosinophilicasthma #drugs

Disclaimer: I am not an immunologist, pulmonologist, rheumatologist, or any other -ologist. Do not take anything I say here (or ever) as medical advice. While I will hopefully have the title Doctor in front of my name (see: Should I Get a PhD?), I will never be an MD, unless I truly lose my senses and go to med school (Don't hold your breath, Dad).

Truth is, I am just a scientifically inclined, pseudo-asthmatic, human pincushion. I say pseudo-asthmatic because my doctors are almost certain I have a rare autoimmune vasculitis. Vasculitis is incredibly challenging to diagnose and in some cases presents with severe refractory asthma or chronic obstructed respiratory disease. Further, I often have high levels of eosinophils (I’ll explain all this in a bit). Therefore, to keep myself healthy and happy, I’ve had to learn to control this eosinophilic asthma-like syndrome.

Over the past year, I have gone from using normal asthma controller medications to intensive immunosuppressives and biologics.

I was fascinated by the asthma biologics, which hold the promise of being asthma cure-alls, reducing prednisone-dependent, severe refractory asthmatics to mild asthmatics.

Part of what makes the biologics so fascinating is the mystery surrounding them. Naturally, I had a lot of questions when my doctors told me that asthma biologics were my best chance of controlling my breathing. Despite their strong opinions that biologics were the answer, they were unable to answer some of my most basic inquiries about them. Generally, I don’t like to let medical professionals stab me without telling me everything there is to know about what’s in the IV. So when my doctors didn't have all the answers, I turned to the Internet, which also came up empty except for a bunch of scientific papers and absolutely riveting FDA reports.

I went on a quest to answer my own questions about each new asthma biologic drug on the market. I wanted answers to two major questions: 1) How do these drugs work in the human body? and 2) What will be my experience receiving one of these shots be like? I could answer the former through extensively combing through the scientific literature and FDA reports, which made for a few very wild Friday nights. The latter I gathered through my own experiences getting the shots. So here it is: the good, the bad, and (my favorite part) the science of asthma biologics all in one place.

The Science

Let's talk about asthma phenotypes. What does phenotype even mean? A phenotype is the distinct observable characteristics of an organism or anything you want to characterize. You can think of phenotypes like you think of dog breeds. Each breed has observable characteristics and these characteristics make you look really smart when you can tell the difference between a Chihuahua and a Great Dane.

What does all this have to do with asthma? For a long time, asthma was treated like there was only one type of dog. When you got an asthma diagnosis, you generically knew that you had chronic small airway inflammation. It is only in the last 20 years that researchers started to distinguish between different sources of inflammation and describe asthma as having different phenotypes.

My sister and I are a great example of this. We both have asthma. Her asthma was always a part of her life, even as an infant. You can still hear the fear in my Mom's voice when she tells the harrowing tale of my sister having an asthma attack and turning blue from hypoxia in the grocery store on a particularly high pollen count day. My asthma story was never like this. I had my first dramatic asthmatic (see what I did there) episode when I was 23 years old. Unlike my sister, I don’t really have seasonal allergies.

Moral of the story is that not all asthma is the same.

A Tale of Many Asthmas

Another asthma blogger and self-proclaimed badassthmatic, Breathin Stephen has already done a really fantastic job outlining the asthma phenotypes in a way that is accessible and easy to understand. I'm going to geek out here and expand a little on what Stephen has already outlined. Additionally, I am summarizing a Nature Medicine review by Dr. Sally Wenzel, a pulmonologist based out of Pittsburgh, PA (Go Pens!).

Researchers used to think that asthma was either allergic or nonallergic. The truth is, it is a lot more complicated than that. A better way to break things down is to think of asthma in terms of Th2-mediated asthma and non-Th2-mediated asthma, which act as umbrellas for different types of asthma.

Th2 refers to a specific immune system cell called a Type 2 helper T cell. Th2 asthma is a subtype of asthma that involves what scientists call a Th2 mediated inflammatory response in your airways. This involves some allergic response and is associated with high levels of something called eosinophils, Immunoglobulin E and activation of Th2 cytokines (IL-5, IL-4, IL-13) which I’ll get into in a bit.

Non-Th2 asthma is a little different, in that it involves other components of the immune system like neutrophils, Th17 pathways, IL-8, and non-immune system related lifestyle factors.

Immune System Lingo

That was a lot to jump into, right? Let’s back up and start at the very beginning.

It might seem obvious, but the goal of the immune system is to protect the body against disease, germs, and anything foreign. This is what white blood cells, also called leukocytes do. You can think of the immune system as an army protecting a castle from invaders. You have different types of soldiers responsible for different tasks so that you don’t have fifty people attempting to fire a cannon simultaneously. The immune system is the same way.

There are five major types of leukocytes: neutrophils, eosinophils, lymphocytes, basophils, and monocytes. I am only going to discuss the former three of those cells here: neutrophils, eosinophils, and lymphocytes.

Neutrophils are the most ubiquitous leukocytes and target super cute things like bacteria and fungi. Eosinophils are a little more ambitious and like to go after larger, sexier parasites, and they also dabble in allergic inflammatory responses.

Lymphocytes are a bit more complicated. What you need to know right now is that they have to do with the T helper cells I mentioned earlier.

So how do these leukocytes fight the good fight? An antibody (Ab) or immunoglobulin (Ig) is a protein made by leukocytes, specifically plasma cells, that the immune system uses to fight pathogens, like the bacterias and viruses that your phlegmy contagious coworker brings and coughs all over the office water cooler. When everything is going right in the body, antibodies only fight off foreign invaders and things that can hurt us. However, this isn't always the case, which requires us to design drugs to stop this from happening. Let's talk about different antibody designations.

Humanized antibodies are antibodies from non-humans that have been modified to make them similar to the corresponding antibody you want to mimic in humans. For example, a popular asthma biologic XOLAIR is made from the cells of a Chinese hamster ovary (I should cite this, but it's on Wikipedia which means it must be true). Humanized antibodies always end in -zumab, like omalizumab and mepolizumab.

Monoclonal antibodies are antibodies that are made from identical immune cells that are genetically identical of a distinct parent cell. Drugs that are monoclonal antibodies always end in -mab, like omalizumab and mepolizumab.

Other Immunoglobulins that I am going to talk about a lot are Immunoglobulin E (IgE) and Immunoglobulin G (IgG). When talking about allergies, IgE reigns supreme. If you have allergies, you probably have slightly higher levels of IgE, which likes to bind with allergens and make you a sniffling hot mess when spring time comes around. There are already a bunch of drugs like antihistamines, antileukotrienes, croticosteroids, and mast-cell stabilizers that you can use to stop IgE from binding with things that make you sniffle.

IgG comes up a lot when you are talking about autoimmune disease. It plays a role in anaphylaxis reactions and is popular when talking about asthma biologics because it can be used to regulate something called cytokines to stop inflammation.

Cytokines are proteins produced by cells that tell other cells what to do with their lives, which is a less technical way to say that they are proteins vital to cell signaling. While they sound similar, cytokines are different from hormones. I have already dropped the word a few time but this is where biologic drugs come in to play. In many systemic diseases, like asthma, you have an overproduction of cytokines that result chronic inflammation and the destruction of other body tissues.

Simply stated, biologics are super bossy cytokine inhibitors, which means that they stop cells from telling other cells to do things that result in systemic diseases.

In the case of most asthma biologics, we are talking about inhibiting a specific type of cytokine called an interleukins. Interleukins (ILs) are cytokines that are made by white blood cells, AKA leukocytes, that act on other leukocytes.

There are a lot of ILs. I am not going to talk about them all because it would make for a terribly dull blog post. There are a few ILs that are associated with Th2 asthma and have corresponding targeting biologics: IL-5, IL-4, and IL-13. That is not to say that these are the only ones involved in asthma or that there are not other biologics in the works for other ILs involved in asthma. These are just the main ones right now.

So when later on I say something about a biologic like: '-zumab is a humanized IgG1, κ monoclonal antibody' you can figure out a few things. First, you know it is a humanized monoclonal antibody because of the suffix. Second, you know that this drug was made in the lab with something freaky like hamster ovaries and was modified to make it similar to what you see in humans. Lastly, you know that the protein that make up this drug is made from identical immune cells that are all clones of the parent cell IgG1. See, no medical degree required.

The only other confusing term I am going to use for the sole purpose of getting the science right is fragment crystallizable region (Fc region). The Fc region of an antibody is what these biologic drugs are going to be binding to to activate or deactivate some immune system component. Think of the Fc region like a wall outlet and the biologic drugs like a plug from a power cord.

Asthma Biologics

XOLAIR® (omalizumab)

What does it target? IgE Fc Region

What conditions does it treat?

XOLAIR treats allergic asthma and chronic idiopathic urticaria (CIU). Allergic asthma is asthma that is triggered by allergens that you inhale like pollen, dust mites, and mold. CIU is a condition that can induce hives for long periods of time (at least 6 weeks) with no specific cause.

How does it work?

Omalizumab is a humanized anti-IgE antibody. It is injected subcutaneously in the fat of the upper arm, thigh, or abdomen. After it is injected, it is slowly absorbed into the bloodstream, where it binds the Fc region of unbound IgE. I already mentioned that IgE likes to bind to allergens and different types of immune cells, which can trigger a whole host of inflammatory responses that exacerbate asthma symptoms and cause hives. If the IgE is no longer able to bind to these allergens and immune cells, there is less of an inflammatory response. This means fewer asthma symptoms and less itchy skin.

What does it cost?

XOLAIR comes in a a powder that your doctor's office prepares to give in an injection. 150 mg of powder for a single injection costs approximately $1,141.

What is the dose?

This depends on factors like the condition you are treating, your blood IgE levels, and body weight. The XOLAIR website has a dosage calculator and charts to determine your dosage and how often you need injections. When I tried XOLAIR, I was receiving 300 mg every 4 weeks.

How often is it needed?

Again, this depends on the condition you are treating, your blood IgE levels, and body weight. Use the dosage calculator link to find out how often you would need XOLAIR.

My experience:

I tried XOLAIR after my first asthma hospitalization, where I was declared status asthmaticus (this is just the fancy phrase for a life-threatening asthma exacerbation) and spent a few days in the respiratory critical care unit. I was on XOLAIR for a few months, which is long enough to start to see it work. It did not help me reduce my steroid dose or reduce my asthma symptoms. Honestly, I didn't notice any changes when I started on XOLAIR. This is mostly because I don't have allergic asthma. From what I have seen scanning the web for other patient experiences, XOLAIR works well if you have CIU or allergic asthma.

I got my XOLAIR shot at my allergist/immunologist doctor's office. They have me call 30 minutes before my appointment time so that they have time to prepare the shot. For my first shot, I had to hang out at my doctor's office for a few hours to make sure I didn't go into anaphylaxis. For every shot after the first, they had me wait 30 minutes. It was a pretty similar experience to getting allergy shots.

NUCALA® (mepolizumab)

What does it target? IL-5

What conditions does it treat?

NUCALA treats severe eosinophilic asthma and refractory eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophilic asthma is a type of severe asthma that is caused by high levels of a specific type of white blood cell called eosinophils. EGPA is a rare type of vasculitis that involves body wide infiltration of eosinophils. A lot of people with EGPA have asthma, which is usually one of the first symptoms.

How does it work?

The exact mechanism of action for mepolizumab is not fully understood (this freaks me out). Here is what we do know: Mepolizumab is a humanized IgG1, κ monoclonal antibody. It is injected subcutaneously in the upper arm, thigh, or abdomen. After it is injected, it is slowly absorbed into the bloodstream where it binds to IL-5. This prevents IL-5 from binding to the IL-5Rα subunit on the surface of eosinophils. Somehow this reduces the production and survival of eosinophils in the blood which can help reduce airway inflammation.

What does it cost?

NUCALA comes in a a powder that your doctor's office prepares to give in an injection. 100 mg of powder for a single injection costs around $3,093.

What is the dose?

This depends on the condition you are treating. If you are receiving NUCALA for severe eosinophilic asthma, it is a 100 mg dose in a single shot. If you are receiving NUCALA for EGPA, it is a 300 mg dose in three separate shots.

How often is it needed?

NUCALA is great because you only need it once every 4 weeks regardless of the condition.

My experience:

NUCALA is what my doctors and I use to control my asthma symptoms. For the most part, it reduces my steroid usage. It is by no means a panacea, but it helps. Another reason my doctors and I chose NUCALA is that I might be one of those super rare people who has EGPA, which NUCALA also treats. The worst side effect I experienced on NUCALA is tiredness and achiness in the days following my injection. Occasionally, I get a small injection site reaction; nothing that a little cortisone cream can't fix. I get my NUCALA shot at my allergist/immunologist’s office. They have me call 30 minutes before my appointment time so that they have time to prepare the shot and they make me wait 30 minutes afterwards in case I have some kind of freaky reaction.

CINQAIR® (reslizumab)

What does it target? IL-5

What conditions does it treat?

CINQAIR treats severe eosinophilic asthma.

How does it work?

Like mepolizumab, the exact mechanism of action for reslizumab is not entirely understood. This is what we do know: reslizumab is a humanized IgG4, κ monoclonal antibody. It is injected intravenously in the bloodstream, where it binds to IL-5. This prevents IL-5 from binding to the IL-5Rα subunit on the surface of eosinophils. Somehow this reduces the production and survival of eosinophils in the blood which can help reduce airway inflammation.

What does it cost?

CINQAIR comes in an intravenous solution that you get at your doctor's office. 10 mL of CINQAIR costs around $963.

What is the dose?

This depends on your body weight. The normal dose for CINQAIR is 3 mg/kg IV.

How often is it needed?

Like NUCALA, CINQAIR is an every 4 weeks thing.

My experience: I have not tried CINQAIR.

FASENRA™ (benralizumab)

What does it target? IL-5Rα chain

What conditions does it treat?

FASENRA treats severe eosinophilic asthma.

How does it work?

I sound like a broken record here but like mepolizumab and reslizumab, the exact mechanism of action for benralizumab is not fully understood by researchers. What we do know with certainty is that FASENRA is a humanized afucosylated IgG1, κ monoclonal antibody. It is injected subcutaneously in the upper arm, thigh, or abdomen. After it is injected, it is slowly absorbed into the bloodstream where it binds to IL-5. This prevents IL-5 from binding to the IL-5Rα subunit on the surface of eosinophils. FASENRA is a little different from NUCALA and CINQAIR because its antibody is afucosylated. This means that benralizumab does not have any fucose sugar units. This lack of sugar units means that natural killer cells bind to FcɣRIII receptors which results in the death of eosinophils through a process call antibody-dependent cell-mediated cytotoxicity. This reduces the umber of eosinophils and can help reduce airway inflammation.

What does it cost?

FASENRA comes in a a solution that your doctor's office administers. For 1 mL of 30 mg/mL it costs around $5,044.

What is the dose?

The recommended dose for FASENRA is 30 mg.

How often is it needed?

This one is a little quirky. FASENRA is administered every 4 weeks for the first 3 doses. After that, it is administered every 8 weeks

My experience: I have not tried FASENRA. My immunologist preferred NUCALA over FASENRA because of long term effectiveness. His claim was that FASENRA works incredibly well at first but over time wanes in effectiveness in a way NUCALA does not.

Aside: You might be thinking: NUCALA, CINQAIR, AND FASENRA all sound insanely similar (except for the afucosylated fun of the FASENRA). If you have eosinophilic asthma, which biologic should you choose? This is a conversation you need to have with you asthma specialist, whether that is an allergist/immunologist or pulmonologist. Your blood eosinophil levels are a significant factor in this determination. For example, CINQAIR requires a higher blood eosinophil level to qualify for insurance coverage than NUCALA and FASENRA.

DUPIXENT® (dupilumab)

What does it target? IL-4Rα

What conditions does it treat?

DUPIXENT treats moderate to severe atopic dermatitis (eczema) and uncontrolled moderate to severe asthma. Eczema is a condition that makes your skin blotchy, red, and incredibly itchy. There is a bit of overlap between people who have eczema and asthma. DUPIXENT also treat moderate to severe asthma that is not necessarily caused by eosinophils.

How does it work?

Dupilumab is a humanized IgG4 monoclonal antibody. It is injected subcutaneously in the upper arm, thigh, or abdomen. After it is injected, it is slowly absorbed into the bloodstream, where it binds to the IL-4Rα subunit, which is shared by IL-4 and IL-13. This prevents IL-4 and IL-13 signaling and cytokine-induced responses. This means there is less release of pro inflammatory cytokines, chemokines, and IgE, resulting in easier breathing, less itchy skin, or both.

What does it cost?

DUPIXENT comes in a a solution that you can administer at home. The cost for 2.28 mL of subcutaneous solution (200 mg/1.14 mL) is approximately $3,161. From what I can tell, the cost is the same for 4.00 mL of solution (300 mg/2.00 mL).

What is the dose?

This depends on the condition. It is also a little different because DUPIXENT requires a loading dose. For eczema, the first dose is 600 mg. Each dose after that is 300 mg. For moderate asthma, the loading dose is 400 mg and each following dose is 200 mg. For severe asthma, the loading dose is 600 mg and each following dose is 300 mg.

How often is it needed?

DUPIXENT is required every 2 weeks, but you can administer it yourself at home.

My experience:

DUPIXENT did not help reduce my asthma symptoms. I wouldn't say that I had a negative reaction to DUPIXENT, but for some reason or another, my asthma got significantly worse after I got my loading dose. DUPIXENT is the most painful of the shots I tried.

Ranking from most to least painful, I would say: 1) DUPIXENT, 2) NUCALA, 3) XOLAIR.

I found that DUPIXENT burned when it was injected. Long story short, after my DUPIXENT shot I ended up taking an ambulance ride where an attractive EMT massacred my arm inserting an IV and spending the evening in an emergency room only to be released and lasting two more days at home before being hospitalized for a full week. While my immunologist does not think I had a specific reaction to the DUPIXENT, he recommended stopping the medication immediately since it clearly didn't help anything and he doesn't like to watch me struggle bus it.

I got my DUPIXENT shot at my allergist/immunologist doctor's office, even though I could have had it shipped to my apartment and stabbed myself. My doctor's office had me call 45 minutes before my appointment time so that they have time to thaw the shot solution to room temperature, and they make me wait 30 minutes afterwards in case I decided to react. Some people, especially those with eczema, swear by DUPIXENT. I am not one of those people. One reason for this might be that I do in fact have eosinophilic asthma or EGPA, which Dupixent isn't specifically designed to treat. Other people experience eye-related effects on DUPIXENT, but that is usually in patients being treated for eczema.

Other Asthma Biologics

I put these biologics in another category because they are not mainstream or approved for asthma patients yet. Another distinguishing factor is that some of them are meant to target non-TH2 mediated asthma. Some of them are so new that they don't have sexy drug company approved names.


What does it target? IL-4Rα

What conditions does it treat?

SEXY NAME TO BE DETERMINED treats asthma and eczema.

How does it work?

According to Wikipedia, It blocks thymic stromal lymphopoietin, an epithelial cytokine. This cytokine is believed to be vital in the initiation and persistence of airway inflammation.

What does it cost?

The yearly cost is probably in the range of an Hermes Birkin bag.

What is the dose?

I think they are still figuring this out.

How often is it needed?

I think they are still figuring this out, too.

My experience: I have not tried SEXY NAME TO BE DETERMINED

Researchers are currently looking into other existing biologics for psoriasis to determine their efficacy for treating asthma. These drugs, SILIQ™ (brodalumab) and COSENTYX® (secukinumab), target IL-17-RA and IL-17A. As of right now, I couldn't find a lot of data on what they do for asthma patients. Another one of these drugs currently not FDA approved to treat anything is risankizumab. It inhibits IL-23/IL-17 signaling which researchers hope will help asthmatic patients with inflammation caused by neutrophils.

Others that never really got off the ground for one reason or another are lebrikizumab, tralokinumab, and pitrakinra. You can find a few articles online on why these medications never made it through trials.

Getting Your Medications

Where do you get these medications? My doctors laughed at me when I assumed I could get these fancy meds at Walgreens or CVS. This was when I learned all about specialty pharmacies. Specialty pharmacies are exactly what they sound like. They typically serve patients with complicated or chronic conditions that require very expensive drugs or challenging dosing regimens. The specialty pharmacy I work with sends my medication to either my doctor's office or my home. Sometimes they are annoying to work with especially when you are setting up insurance and copayment programs and first time delivery, but it gets easier. I find calling the numbers they give you gets results (and medications) the fastest.

Paying For Your Medications

One thing all these medications have in common is that they are wicked expense. Thankfully, they also have corresponding copay assistance programs. They work by covering your insurance copayment up to a certain amount per year if you meet their listed criteria. I wrote about these programs in my blog post, The Price of Being Wheezy. If I am not swamped with work or feeling too lazy, I might write another post about dealing with these copayment programs.

What I Learned From Trying These Drugs

My pulmonologist is a much more careful person than I am. We recently had an argument about whether I should do a methacholine challenge. He said, “Hell no.” I said, “Hell yes.” He won. Ultimately, it would be too risky without providing any reward other than satisfying my curiosity. I am more likely to jump on a given trend or try something for the sake of trying something. This isn’t always the best approach, and has gotten me into my fair share of trouble. Ask anyone who knows me.

Looking back on my experience with asthma biologics, I wish I had taken an approach more similar to what my pulmonologist recommended. While nothing bad happened to me from taking biologics, there are so many unknowns. Additionally, my doctors and I didn’t know what we needed to treat or if the biologic was the right fit. We knew only if I fit the qualifications for insurance purposes. These drugs should be taken carefully, and only after you have narrowed down the problem you are trying to treat and determined that the risks are outweighed by the benefits.

The Future of Asthma Drugs

Asthma biologics are so alluring to researchers and doctors because they stop inflammatory responses earlier on in the chronic inflammatory disease pipeline than existing inhaled and oral treatments. Think of it this way: if someone caused a leak in your roof by pouring a bucket of water on it every day, would you prefer to fix the leak or stop the maniac who keeps pouring the bucket of water? I would prefer to get rid of the maniac, because I know if I don't, I will definitely have a leak in my roof again. This seems like the future of treating chronic inflammatory conditions like asthma. By stopping inflammation before it becomes a problem in people with very mild to incredibly severe asthma, asthmatics can stop perpetually plugging the hole in their roof and live healthier (and less inflamed) lives.

However, these biologic treatments will not become available to people with less severe asthma until the price tag drops by about $20,000. For someone like me, who has severe asthma flare ups that land me in critical care units, I can run up a hospital bill of $50,000 in the course of a few days. My insurance would much rather pay for me to take a drug like NUCALA than pay for several hospital stays per year. For someone who simply requires basic asthma inhalers to manage their health, it is a lot harder to justify the cost, which is why they are reserved for the most severe cases. Hopefully, this will change with further scientific development and time.

Also, biologics are still not a comprehensive cure. Until scientists figure out the exact underlying mechanisms that result in the cytokine excess, they won't have a cure. At the end of the day, biologics take us a step closer to finding a cure for diseases like asthma, eczema, EGPA, psoriasis, etc., but they still don't explain how the maniac who is pouring water on the roof got onto the roof. In the meantime, while we figure it out, we can breathe a little easier.



© 2020 by Claire N. Saunders.