Trying Another Biologic for RA

Medically Reviewed by David Zelman, MD on December 15, 2021
4 min read

Biologic drugs can be joint savers for rheumatoid arthritis (RA). But even these powerful medications don't always guarantee relief from pain and stiffness.

Sometimes the first biologic you try doesn't work for you. Or a drug might control your RA for a while, only to stop working. It's hard to predict whether one of these drugs will be a hit or a miss.

"We have a lot of really great medications that work very well" against rheumatoid arthritis, says Rebecca Haberman, MD, a rheumatologist at NYU Langone Health. "But the thing we're missing is knowing which medication is best for which patient right off the bat."

If one biologic isn't a good fit, don't worry. Your doctor will try others and will keep trying until they find something that helps you.

Biologics usually aren't the first drug you take for RA. They most often come in after you've tried a standard disease-modifying antirheumatic drug (DMARD) like methotrexate. (You might start with a biologic if you can't take methotrexate.)

Your doctor will choose a biologic drug that's safe for any other health conditions you have and that fits the kind of treatment you prefer. 

Nilasha Ghosh, MD, a rheumatologist at the Hospital for Special Surgery, often starts her patients on a TNF inhibitor like adalimumab (Humira), etanercept (Enbrel), or infliximab (Remicade). That's because these medications have been around for long enough to confirm that they're safe and they work.

But some people who try a TNF inhibitor will have to switch drugs for one of three reasons.

The first drug isn't helping

The first medication you try might not work at all, or barely help with your symptoms. Your doctor will call that a "primary failure" or say you're a "non-responder."

That's not a reflection on you or anything you did. The medication just wasn't a good fit for you.

Before you switch to something else, you need to give the drug enough time to work. It can take 3-4 months to start seeing improvement on a new biologic, Haberman says.

It worked for a while, but now it doesn't

More commonly, a biologic will start working and then stop. "Over time it loses its potency and a patient's arthritis can worsen," Ghosh says.

One way to tell that your biologic has lost its punch is that you feel better soon after your injection, but your joint pain starts to sneak back in before you're due for your next shot.

That's called secondary failure. It happens because your body makes antibodies against the biologic. Antibodies neutralize the drug and make it less potent.

"That's one of the reasons we often give methotrexate with the biologics. Methotrexate can prolong the lifespan of biologics by stopping you from making antibodies," Haberman says.

The biologic caused side effects

Biologics are safe drugs overall. But because they suppress your immune system to stop it from attacking your joints, they increase your risk for infections.

These drugs can also cause side effects like:

  • Skin rashes
  • Cold symptoms
  • Diarrhea
  • Nausea
  • Belly pain

Some side effects are mild enough to tolerate. Others can bother you enough to make you want to switch medicines.

Before changing your treatment plan, your doctor will ask if you've taken your biologic just as prescribed. A few skipped doses could affect your results.

If that's not the problem, your doctor might add an oral DMARD to your biologic. The main one is methotrexate, Haberman says. Hydroxychloroquine (Plaquenil) and leflunomide (Arava) are other choices.

Biologics and DMARDs both target the immune system, but in different ways. "Sometimes, the two can work in tandem for a superior therapeutic response," Ghosh says.

Your doctor could also switch you to another biologic. Again, it can take some guesswork to find the second drug that's right for you.

"Usually if people have primary failure, meaning that I start them on a medication and it doesn't work at all, I will try to switch them to another class of medication because it seems like that target might not be right for them," Haberman says.

For example, you might switch from a TNF inhibitor to an interleukin inhibitor. These two drugs target different types of cells involved in your body's immune response.

If you had a great response to the first biologic but it stopped working, it could be the right target but the wrong delivery method. In that case, your doctor can switch you to a different drug in the same class.

The new biologic might work better for you. Then again, it might not.

"There really is no way of knowing," Haberman says. "Each medication is different -- even medications in the same class."

Side effects are another question mark with a new drug. They're different for each biologic class and type. "Side effects can come not only from the medication itself, but also the delivery system -- the way the company has designed the needle or pen," she says.

Some people find the right biologic on the first try. Others go through a few of these drugs without any success.

"Finding the right medication, or combination of medications, can be very frustrating for patients," Ghosh says. If a drug isn't helping you, she says communicating with your doctor is key to figuring out your next steps.

If you're starting to get discouraged, remember that there are a lot of treatment options for RA. They include several types of biologics, other DMARDs, and lifestyle changes like exercise and weight loss.

Plus, new RA drugs are in the pipeline. "There is a lot of research going into the discovery of new biologics, so I always offer up some hope of a new medication that may work better for a patient in the future," Ghosh says.