Biologics in Severe Asthma: How Anti-IgE and Anti-IL-5 Therapies Work

When inhalers aren’t enough

For people with severe asthma, standard treatments like inhalers and oral steroids often fall short. Even with daily use, they might still wake up gasping, end up in the ER, or rely on monthly steroid bursts just to stay stable. That’s where biologics come in. These aren’t your typical pills or sprays-they’re precision drugs made from living cells, designed to shut down specific parts of the immune system driving asthma flare-ups. Two of the most established types target anti-IgE and anti-IL-5 pathways. They don’t cure asthma, but for the right patients, they can turn a life of constant fear into one with real breathing room.

What is anti-IgE therapy?

Omalizumab (brand name Xolair) was the first biologic approved for asthma back in 2003. It works by latching onto IgE, the antibody that triggers allergic reactions. In allergic asthma, IgE binds to mast cells and basophils, causing them to dump histamine and other inflammatory chemicals into the airways. Omalizumab blocks that binding, preventing the chain reaction before it starts.

This therapy is only for people with confirmed allergic asthma. You need to test positive for at least one perennial allergen-like dust mites, pet dander, or cockroach proteins-and have serum IgE levels between 30 and 1500 IU/mL. It’s not for everyone with asthma, only those whose symptoms are tied to allergies. Studies show it cuts asthma attacks by about 50% in the right group. The INNOVATE trial found patients had fewer ER visits, fewer hospital stays, and needed less oral steroids after starting treatment.

Dosing is based on your weight and IgE level. Most people get an injection every 2 to 4 weeks. It’s given under the skin, often with an auto-injector pen. Side effects are usually mild: headache, sore throat, or a red, itchy spot at the injection site. But there’s a small risk-about 1 in 1,000 doses-of a serious allergic reaction called anaphylaxis. That’s why you’re asked to wait 30 minutes after your first few doses.

What is anti-IL-5 therapy?

While anti-IgE targets allergies, anti-IL-5 therapies go after a different problem: eosinophils. These are white blood cells that swell up in the airways of some asthma patients, causing chronic inflammation. High levels mean more flare-ups, more damage, and more reliance on steroids.

Three drugs fall under this category: mepolizumab (Nucala), reslizumab (Cinqair), and benralizumab (Fasenra). Mepolizumab and reslizumab bind directly to IL-5, the signal that tells eosinophils to multiply. Benralizumab goes one step further-it binds to the IL-5 receptor on the eosinophils themselves, tricking the immune system into killing them off. This is called antibody-dependent cellular cytotoxicity, or ADCC. Within 24 hours of a benralizumab shot, blood eosinophil counts can drop by over 95%.

To qualify, you need to have eosinophilic asthma. That means your blood eosinophil count has been 150 cells/μL or higher in the past year, or 300 cells/μL or higher. Your doctor will check this with a simple blood test. These drugs aren’t meant for non-eosinophilic asthma. If your eosinophils are low, they won’t work.

Benefits are strong: mepolizumab reduced exacerbations by 52% in the MENSA trial. Benralizumab cut them by 51% in the ZONDA trial. Many patients report fewer hospitalizations and can cut or stop oral steroids entirely. Reslizumab is the only one given as an IV infusion-every 4 weeks-which means you have to go to a clinic. The others are self-injected at home.

How do they compare?

Choosing between anti-IgE and anti-IL-5 isn’t about which is “better.” It’s about which matches your asthma type.

One key difference: benralizumab doesn’t just block IL-5-it kills eosinophils fast. That’s why some patients see results quicker. But if you have both allergies and high eosinophils, your doctor might consider both pathways. Tezepelumab (Tezspire), approved in 2021, is newer and targets TSLP, an upstream signal that drives multiple inflammation types, even in non-eosinophilic asthma. It’s an option if you don’t fit neatly into either category.

Who qualifies-and who doesn’t

Biologics aren’t first-line. Before even thinking about them, your doctor needs to confirm you’re doing everything right with standard care. That means:

• Your inhaler technique is perfect (many patients think they’re using them right, but they’re not)
• You’re taking your meds consistently
• You’ve ruled out triggers like smoking, uncontrolled allergies, or GERD
• You’ve tried high-dose inhaled corticosteroids plus a long-acting beta agonist

If you’ve done all that and still have 2 or more flare-ups a year, or need oral steroids more than twice in 12 months, you might be a candidate. But not everyone responds. Real-world data shows 30-40% of patients don’t get meaningful improvement. That’s why biomarkers are critical. If your IgE is too low or your eosinophils are normal, the drug won’t work-no matter how bad your asthma feels.

Cost, access, and daily reality

These drugs cost between $25,000 and $40,000 a year in the U.S. Insurance rarely covers them without prior authorization, which can take 2-3 weeks. Even then, you might need to try cheaper options first. In New Zealand and other countries with public healthcare, access is tighter-only patients with the most severe, uncontrolled asthma get approved.

Most patients learn to self-inject after 2-3 supervised sessions. The pens are simple, but anxiety about needles is common. Some report mild pain or bruising at the injection site, especially at first. But for many, the trade-off is worth it. One Reddit user, u/AsthmaWarrior2020, said after six months on mepolizumab, his ER visits dropped from 3-4 a year to zero. He stopped daily prednisone.

But it’s not perfect for everyone. Another user, u/BreathlessInSeattle, had to quit benralizumab after three doses because of severe joint pain. Side effects like this are rare but real. The risk of anaphylaxis is low, but you need to know the signs: swelling, trouble breathing, dizziness. Always carry an epinephrine auto-injector if your doctor recommends it.

What to expect over time

Don’t expect instant results. Some people feel better in 4 weeks. Others take 12-16 weeks. Patience is key. Your doctor will track your asthma control with tools like the Asthma Control Test and monitor your blood eosinophils or IgE levels every few months.

Many patients see big improvements in quality of life. A 2023 survey found 78% of users felt more in control of their asthma, and 65% were able to reduce or stop oral steroids. That’s huge-because long-term steroid use can cause weight gain, bone loss, diabetes, and mood changes.

But biologics aren’t a cure. You still need your inhalers. You still need to avoid triggers. You still need to see your specialist. They’re powerful tools, but they work best as part of a full plan-not a replacement for good asthma management.

The future of asthma treatment

The field is moving fast. New biologics are in development, including ones you’d only need twice a year. Researchers are also testing combinations-like pairing anti-IgE with anti-IL-5-to see if hitting multiple pathways works better. AI tools are being built to predict who will respond based on blood markers, lung function, and even genetic data.

For now, the message is clear: if you have severe asthma that’s not under control, talk to your allergist or pulmonologist about biologics. Don’t assume you’re out of options. For the right person, these drugs can mean the difference between living with asthma and living beyond it.