Biosimilar Switching: What Happens When You Change from Originator

When you’ve been on a biologic drug for years-maybe for rheumatoid arthritis, psoriasis, or Crohn’s disease-the last thing you want is to suddenly be switched to something new. Even if your doctor says it’s the same thing, your body might feel different. That’s the reality of biosimilar switching: moving from the original biologic drug to a biosimilar version, often because of cost. But what actually happens when you make the switch? Is it safe? Does it work the same? And why do some people feel worse-even when labs say nothing’s changed?

What Exactly Is a Biosimilar?

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 biological drugs made from living cells-like infliximab, adalimumab, or etanercept. These drugs are made by living organisms, so even the original version isn’t perfectly identical from batch to batch. A biosimilar doesn’t have to be identical-it just has to be highly similar in structure, function, and effect. Regulatory agencies like the FDA and EMA require over 250 analytical tests to prove this. They look at protein shape, purity, how the drug binds to targets, and how it behaves in the body. Then they test it in clinical trials to make sure it works just as well and is just as safe.

The first biosimilar approved in the U.S. was Zarxio (filgrastim-sndz) in 2015. Since then, 37 biosimilars have been approved, mostly targeting TNF inhibitors used for autoimmune diseases. In Europe, biosimilars are used in 67% of filgrastim cases. In the U.S., that number is only 24% for infliximab-partly because of patent strategies and insurance rebates that make originators cheaper than they should be.

Switching from Originator to Biosimilar: The Evidence

More than 80 studies have looked at switching from originator biologics to biosimilars. The largest, the NOR-Switch trial, followed 481 patients with inflammatory arthritis or IBD who were switched from originator infliximab to the biosimilar CT-P13. After one year, 52.6% were still on the biosimilar. The group that stayed on the originator? 60%. The difference wasn’t statistically significant. That means: no real drop in effectiveness or safety.

Other studies back this up. In psoriasis patients switching from adalimumab to its biosimilar, drug retention rates were nearly identical: 79% vs. 81%. In Crohn’s disease, 90.6% of patients stayed in remission after switching from one biosimilar (CT-P13) to another (SB2). Trough levels-the amount of drug in the blood-didn’t change meaningfully. Fecal calprotectin, a marker of gut inflammation, stayed the same. Immunogenicity-the body making antibodies against the drug-was low. One study tracked patients who switched three times: originator → biosimilar → another biosimilar. Only 3 out of 100 patient-years developed new antibodies. No increase in serious side effects.

The FDA analyzed 22 switching studies involving 5,700 patients. They found no increase in death, serious infections, or treatment discontinuation. The EMA says switching between originators and biosimilars is not expected to compromise safety. These aren’t opinions. These are conclusions from data collected over years, across countries, in real-world clinics.

Why Do Some People Feel Worse After the Switch?

Here’s the twist: even when the science says everything’s fine, patients sometimes report feeling worse. Fatigue. Joint pain. Skin flare-ups. New injection site reactions. But their blood tests? Normal. Their disease scores? Stable.

This isn’t a failure of the biosimilar. It’s the nocebo effect-the opposite of placebo. If you believe the new drug won’t work as well, your brain can make you feel worse. 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 the system, not their doctor. On Reddit’s r/rheumatoidarthritis forum, over 140 threads from 2020 to 2023 describe patients who “felt the difference” after switching, even though their doctors saw no clinical change.

Real discontinuation rates? Around 4% to 18%. But here’s the key: most of those aren’t because the drug stopped working. They’re because patients felt something was off. In one study, 12.6% of patients stopped etanercept biosimilars-even though their disease activity didn’t worsen. In another, 7.8% reported injection site reactions with adalimumab biosimilars, compared to 10.7% with the originator. That’s not worse-it’s similar.

Psychology matters. If you’re told, “They’re switching you because it’s cheaper,” you’re more likely to believe it won’t work. If you’re told, “This is an exact copy approved by the same agencies as your original drug,” your brain responds differently.

Biosimilar to Biosimilar: Is That Safe Too?

Now imagine switching again-from one biosimilar to another. Sounds risky? It’s not. The NOR-SWITCH II study followed patients who switched multiple times over two years. Eighty-nine percent were still on treatment. Another study in Spain showed a slightly higher discontinuation rate (15.3%) after switching from CT-P13 to SB2 in IBD patients-but the drug levels in their blood were unchanged. So why did they stop? Likely because of perception, not performance.

In Germany, patients switched from SB4 to GP2015 with no drop in effectiveness. In Denmark, switching between adalimumab biosimilars showed no difference in skin clearance. The data is clear: switching between biosimilars doesn’t increase risk. But regulatory agencies are split. The FDA requires special studies to approve a biosimilar as “interchangeable”-meaning a pharmacist can swap it without doctor approval. Only one adalimumab biosimilar (Cyltezo) has that designation so far. The EMA doesn’t require it. They say all biosimilars are switchable.

Cost and Access: The Real Reason for Switching

Biosimilars cost 15% to 35% less than originators. In 2023, Humira biosimilars launched at a 35% discount. That’s billions saved for health systems. In Europe, where biosimilars are widely adopted, patients get access to drugs they couldn’t otherwise afford. In the U.S., 85% of health plans now require patients to switch to biosimilars-especially if they’re on long-term therapy.

But cost savings aren’t automatic. Insurance companies sometimes make originators cheaper through rebates. That’s why U.S. adoption lags behind Europe. Still, the trend is clear: biosimilars are here to stay. By 2025, $178 billion in biologic patents will expire. More biosimilars are coming-for IL-17 inhibitors, IL-23 blockers, even monoclonal antibodies for cancer.

What Makes a Safe Switch?

Switching isn’t just about swapping pills. It’s a process. The PERFUSE study showed that with good communication, discontinuation dropped from 18% to just 6.4%. How? Three things:

1. Pre-switch counseling: At least 20 minutes with your doctor. Explain what biosimilars are. Show the data. Answer questions.
2. Shared decision-making: Don’t just tell the patient. Ask: “What are your concerns?”
3. Post-switch monitoring: Check disease activity at 3 months. Measure trough levels if needed. Don’t assume a flare is the drug’s fault.

Doctors who do this-rheumatologists, gastroenterologists-see fewer dropouts. Patients who feel heard stay on treatment. It’s not magic. It’s basic care.

Who Should Avoid Switching?

Not everyone should switch. If you’re in a flare-your DAS28 score is above 5.1, your Crohn’s disease activity index is high, your PASI score is over 10-hold off. Stability matters. Switching during active disease increases the chance of misattributing a flare to the new drug.

Also, if you’ve had multiple switches before, or if you’ve developed antibodies to the originator, proceed with caution. The data is limited here. But for most people-stable, on long-term therapy, with no history of bad reactions-switching is safe.

The Future of Biosimilar Switching

Interchangeable biosimilars are the next step. In 2024, Cyltezo became the first interchangeable adalimumab biosimilar in the U.S. That means pharmacies can swap it automatically-just like generics. This will drive down prices even further. More patients will get access. More health systems will save money.

But the real challenge isn’t science. It’s trust. Patients need to believe these drugs are safe. Doctors need to feel confident prescribing them. Pharmacists need to know how to explain them. The data is solid. The evidence is overwhelming. Now it’s about communication.

Switching from an originator to a biosimilar isn’t a downgrade. It’s a smart, science-backed move. The drug works the same. The risks are the same. The savings are real. And for millions of people around the world, it might be the only way they can keep getting the treatment they need.