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

What Are Biologics for Severe Asthma?

Severe asthma doesn’t respond well to standard inhalers, even when used correctly. For these patients, biologics offer a new path forward. These aren’t regular pills or sprays. They’re lab-made proteins-monoclonal antibodies-that zero in on specific parts of the immune system driving inflammation in the lungs. Think of them like precision missiles instead of scatter shots.

Two major classes of biologics dominate treatment today: anti-IgE and anti-IL-5. Omalizumab (Xolair) targets immunoglobulin E, the antibody responsible for allergic reactions. Anti-IL-5 drugs-mepolizumab (Nucala), reslizumab (Cinqair), and benralizumab (Fasenra)-block interleukin-5, a signal that tells eosinophils (a type of white blood cell) to swarm the airways and cause swelling.

These treatments are only for people whose asthma stays out of control despite high-dose inhaled steroids and long-acting bronchodilators. They’re not first-line. They’re for when everything else has failed.

How Anti-IgE Therapy (Omalizumab) Works

Omalizumab is the original biologic for asthma, approved back in 2003. It binds to free IgE in the bloodstream before it can attach to mast cells and basophils. When IgE can’t latch on, those cells don’t release histamine and other inflammatory chemicals that trigger wheezing, coughing, and tightening of the airways.

This therapy works best for people with allergic asthma. You need proof of allergy-either a positive skin test or elevated specific IgE levels to things like dust mites, pet dander, or pollen. Your total serum IgE must be between 30 and 1500 IU/mL. If you don’t have allergies, omalizumab won’t help.

It’s given as a subcutaneous injection every two to four weeks, depending on your weight and IgE level. Most people start feeling better after 12 to 16 weeks. Some notice improvements sooner, but patience is key. You can’t skip doses. The effect builds over time.

How Anti-IL-5 Therapies Target Eosinophilic Asthma

Not all severe asthma is allergic. Some people have high levels of eosinophils in their blood or lungs-often without clear triggers. This is called eosinophilic asthma. That’s where anti-IL-5 drugs come in.

Mepolizumab and reslizumab directly bind to IL-5, stopping it from activating eosinophils. Benralizumab goes a step further: it attaches to the IL-5 receptor on eosinophils themselves and triggers their destruction. This means eosinophil counts can drop by over 95% within 24 hours after a benralizumab shot.

To qualify, you typically need a blood eosinophil count of at least 150 cells/μL in the past year-or 300 cells/μL if you’ve had recent flare-ups. These drugs don’t care if you’re allergic. They care about your eosinophils.

Dosing varies: mepolizumab and benralizumab are injected under the skin every 4 weeks (benralizumab switches to every 8 weeks after the first three doses). Reslizumab requires an IV infusion every 4 weeks, which means a clinic visit each time.

Real-World Results: What Patients Actually Experience

Clinical trials show biologics reduce asthma attacks by 40% to 60%. That’s not just numbers-it means fewer ER trips, fewer hospital stays, and less need for oral steroids like prednisone.

One patient in the UK, on mepolizumab, went from four emergency visits a year to none. Another, on benralizumab, stopped taking daily steroids and started hiking again. But it’s not universal. About 30% to 40% of people don’t respond at all. That’s why matching the right drug to the right patient matters.

Side effects are usually mild: soreness at the injection site, headache, or a sore throat. About 1 in 10 people get these. Anaphylaxis is rare-around 1 in 1,000 doses-but more likely if you’ve had severe allergies before. That’s why the first few doses are given in a medical setting.

Some people report joint pain or fatigue. One Reddit user stopped benralizumab after three shots because of severe joint pain, even though their asthma improved. Others swear by it. Individual responses vary.

Who Should Get These Treatments-and Who Shouldn’t

Before starting any biologic, your doctor needs to confirm three things:

1. You’re using your inhalers correctly and consistently.
2. Your asthma is truly severe-frequent attacks, hospitalizations, or steroid dependence.
3. You have the right biomarker: IgE for omalizumab, eosinophils for anti-IL-5 drugs.

If you’re a non-allergic, non-eosinophilic asthmatic, these drugs won’t help. Trying them anyway is a waste of time and money. Biomarker testing isn’t optional-it’s required.

Also, biologics don’t replace your regular asthma meds. You still need your inhalers. They’re add-ons, not replacements.

Children as young as six can get omalizumab. Anti-IL-5 drugs are approved for ages 12 and up. No one under 6 gets biologics yet, though trials are ongoing.

Cost, Access, and Insurance Hurdles

These drugs are expensive. Annual costs range from $25,000 to $40,000 in the U.S. In the UK, they’re available through the NHS, but access isn’t automatic. You need to go through a specialist asthma clinic and prove you meet strict criteria.

Insurance approval can take 14 to 21 days. Many patients wait months before getting started. Manufacturer support programs help with co-pays and provide nurses to train you on self-injection.

Most people learn to inject themselves after two or three supervised sessions. Auto-injector pens make it easier than you’d think. But you still need to keep up with appointments and blood tests to monitor eosinophils or IgE levels.

The Bigger Picture: Where This Is All Heading

Biologics have changed the game for severe asthma. But we’re still early in this journey. Tezepelumab (Tezspire), approved in 2021, targets TSLP-an upstream protein that triggers multiple inflammatory pathways. It works even if you don’t have high eosinophils or IgE. That’s a big deal.

Now, researchers are testing twice-yearly injections. Imagine getting a shot only twice a year instead of every month. Phase 3 trials are underway. Oral biologics are also in development, though none are approved yet.

The goal isn’t just to reduce attacks. It’s to restore quality of life. People on these drugs report sleeping better, working full-time, and not fearing the next cough. That’s the real win.

But cost and access remain huge barriers. Only 1-2% of eligible patients in the UK and Europe are on biologics. The gap between who could benefit and who actually gets treated is wide.

What Comes Next?

If you or someone you know has severe asthma that won’t quit, ask your specialist about biomarker testing. Don’t assume you’re not a candidate. Many people are turned away because they didn’t get tested properly.

Keep track of your attacks, your steroid use, and your lung function. Bring that data to your appointment. It helps your doctor decide if a biologic makes sense-and which one.

And remember: biologics aren’t magic. They’re powerful tools, but they work best when paired with good asthma management, avoidance of triggers, and regular follow-ups.