Biosimilar Switching: What Happens When You Change from Originator

When you’ve been on a biologic drug for years - say, adalimumab or infliximab - your body knows it. Your symptoms are under control. Your bloodwork is stable. Then your doctor says, "We’re switching you to a biosimilar." Suddenly, you’re not just changing a pill. You’re changing a treatment that’s become part of your life. What actually happens when you make that switch? And is it safe?

What Is a Biosimilar, Really?

A biosimilar isn’t a generic. That’s the first thing to understand. Generics are exact copies of small-molecule drugs like aspirin or metformin. Biosimilars are copies of complex biologic drugs made from living cells - proteins, antibodies, or other large molecules. Because they come from living systems, no two batches are ever identical. Even the originator drug changes slightly over time. That’s why biosimilars aren’t called "identical" - they’re called "highly similar." Regulators like the FDA and EMA require biosimilars to match the originator in quality, safety, and effectiveness. They run over 250 analytical tests comparing structure, purity, and function. Then they test pharmacokinetics - how the body absorbs and processes the drug - in healthy volunteers. Finally, they look at clinical outcomes in patients with the same condition. Only if there’s no clinically meaningful difference is it approved.

Since 2006, more than 37 biosimilars have been approved in the U.S. alone. Most target common biologics used for rheumatoid arthritis, psoriasis, Crohn’s disease, and ulcerative colitis. The biggest ones? Infliximab and adalimumab. These drugs cost over $2,000 per dose. Biosimilars? They launch at 15% to 35% lower prices. That’s billions saved for health systems every year.

Switching from Originator to Biosimilar: What Does the Data Say?

The biggest fear patients have is: "Will my disease flare?" The answer, based on dozens of studies, is no - not if you’re stable.

The NOR-Switch study, which tracked 481 patients with rheumatoid arthritis, psoriatic arthritis, or inflammatory bowel disease, found that switching from originator infliximab to its biosimilar CT-P13 had nearly the same retention rate after one year: 60% stayed on the originator, 52.6% stayed on the biosimilar. The difference? Not statistically significant.

Other studies confirm this. In IBD patients switching from CT-P13 to another biosimilar, SB2, 90.6% maintained remission. Fecal calprotectin - a marker of gut inflammation - stayed almost exactly the same before and after. In psoriasis patients, drug retention after switching to adalimumab biosimilars was 79%, compared to 81.3% before switching. No major safety red flags.

Even more telling: immunogenicity - the body making antibodies against the drug - didn’t spike after switching. One study followed 140 patients through two switches (originator → biosimilar → another biosimilar). Only 3 out of 100 patient-years developed new antibodies. That’s lower than the natural rate of antibody development in people staying on the originator.

For patients with stable disease - DAS28 scores below 3.2 in arthritis, or low calprotectin in IBD - switching is not just safe. It’s well-supported by evidence.

Why Do Some People Stop Taking Their New Medication?

If the science says it’s safe, why do 4% to 18% of patients stop after switching?

It’s rarely because the drug stopped working. It’s because they felt like it did.

A 2021 study in Frontiers in Psychology found that 32.7% of patients reported new or worsening symptoms after a non-medical switch - meaning they were switched by a pharmacist or insurer, not their doctor. These symptoms included fatigue, joint pain, or skin flares. But lab tests? Normal. Inflammation markers? Unchanged. The only thing that changed was the brand name on the bottle.

This is the nocebo effect - the opposite of placebo. If you believe a change will make you worse, your brain can make it so. Reddit threads from patients with rheumatoid arthritis are full of posts like: "I switched to the biosimilar and suddenly I can’t walk. My doctor says everything looks fine, but I know something’s off."

Real side effects do happen - but they’re rare. Injection site reactions? About 7.8% in some adalimumab biosimilar studies. But these are usually mild and temporary. Serious adverse events? No increase compared to the originator. Death? No difference. The FDA analyzed 5,700 patients across 22 switching studies and found zero increase in risk.

So when someone says, "I switched and I felt worse," they’re not lying. But the cause isn’t always the drug.

What About Switching Between Biosimilars?

Some patients are switched twice - first from originator to biosimilar, then from one biosimilar to another. Is that safe?

Yes, if done carefully. The NOR-SWITCH II extension study followed patients for two years and found 89.2% stayed on therapy after multiple switches. Trough levels - the amount of drug in your blood - stayed steady. Immunogenicity didn’t climb.

But there are outliers. A 2022 Spanish study found a 15.3% discontinuation rate after switching from CT-P13 to SB2 in IBD patients - higher than the 8.7% in patients who never switched. Yet their drug levels were nearly identical. Why? The authors suspect psychological factors, not biological ones.

Experts agree: switching between biosimilars is acceptable in stable patients. But it should never be done without discussion. You shouldn’t be switched back and forth like a ping-pong ball.

How Is Switching Done Right?

The difference between a smooth switch and a disaster? Communication.

The PERFUSE study showed that when patients had a 20-minute counseling session before switching, discontinuation dropped from 18% to just 6.4%. What happened in that session? The doctor explained: why the switch was happening, how biosimilars work, what side effects to watch for, and how to report problems. Patients were given a written summary and a follow-up appointment in three months.

Good switching means:

1. Only switch if your disease is stable - no recent flares, no active infections.
2. Don’t switch during pregnancy, major surgery, or if you’re on multiple biologics.
3. Get informed consent. You should understand the change.
4. Track your symptoms and lab markers before and after.
5. Check drug levels (trough levels) if possible - especially in IBD or RA.
6. Follow up in 8-12 weeks. Don’t wait six months.

It’s not about the drug. It’s about the process.

Why Do Some Countries Handle This Differently?

Europe and the U.S. have different rules. In the EU, any approved biosimilar can be substituted at the pharmacy. No doctor’s note needed. In the U.S., only "interchangeable" biosimilars can be swapped automatically. As of 2024, only one adalimumab biosimilar (Cyltezo) has that designation.

Why the difference? The FDA wants proof that switching back and forth won’t cause harm. The EMA trusts the data and says the risk is too low to require extra studies. Neither is wrong. Europe moved faster because they had more pressure to cut costs. The U.S. moved slower because of legal battles over patents and rebates.

Canada takes a different view. Their health agency warns that biologics are too complex to be "copied" exactly. They recommend staying on the same product unless there’s a strong reason to switch. That’s a cautious stance - and one that’s still common among some doctors.

What’s Next?

The market is exploding. Over $178 billion in biologic patents will expire by 2025. More biosimilars are coming - for drugs like rituximab, etanercept, and even insulin. Health plans are already mandating switches. By 2023, 85% of U.S. insurers required patients to switch to biosimilars if available.

That’s good for the system. But it’s not good for patients if they’re forced without support. The goal isn’t just to save money. It’s to save money without losing health.

The evidence is clear: switching from originator to biosimilar is safe for most people. But safety isn’t just about blood tests and antibody levels. It’s about trust. It’s about feeling heard. It’s about knowing you’re not being treated like a cost center.

If you’re being asked to switch, ask questions. Ask for data. Ask for time. Ask for a plan. You’re not just changing a drug. You’re changing your care. And you deserve to be part of that decision.