an illustration that shows different biologic medication syringes and auto-injector pens
Credit: Tatiana Ayazo

Key Takeaways

  • Among rheumatoid arthritis patients who “failed” a TNF biologic, there wasn’t much difference in terms of reaching remission or low disease activity whether they switched to a different TNF or tried a different type of biologic.
  • Given the growing number of treatment options for RA, more research is needed to help doctors and patients figure out the right medication for a given patient.

People with rheumatoid arthritis (RA) who don’t fare well enough on methotrexate alone or can’t tolerate it are generally advised to start a TNFi biologic. (This is an intravenous medication — given by injection or infusion — that targets specific parts of the immune system to reduce overactivity and inflammation.)

But there are several drugs in this class, and the first one your doctor puts you on may or may not work for you. If you don’t reach remission (or low disease activity) with the first TNF biologic you try, what should your next move be? Should you try a different TNF, or would you be better off moving on to a different class of medication?

In the 2021 update of its Guideline for the Treatment of Rheumatoid Arthritis, the American College of Rheumatology recommended that people on a biologic who have not yet reached their treatment target might be better off switching to a drug in a different class than trying a second drug in the same class. This advice was “conditional,” since there was only weak evidence supporting it.

Recently, a group of rheumatologists led by Jeffrey Curtis, MD, decided to examine the hypothesis that changing to a new drug class would enable more RA patients who didn’t do well on a first TNFi to reach low disease activity. (Dr. Curtis is also a co-principal investigator of ArthritisPower, our patient-centered research registry.)

In their observational study, which was published in the journal ACR Open Rheumatology, researchers analyzed data on 939 rheumatoid arthritis patients who “failed” the first TNF biologic they tried. (“Failing” a drug is commonly used phrase in the research world. However, we acknowledge that what it really should mean is not that someone failed to do well on a medication, but rather that the medication failed to work well enough for them.

  • About 54 percent of these patients went on to use a non-TNFi drug such as abatacept (Orencia, a biologic that interferes with T cells in the immune system), rituximab (Rituxan, a biologic that interferes with B cells in the immune system), or tocilizumab (Actemra, a biologic that blocks the immune system protein interleukin-6, or IL-6).
  • About 46 percent stayed within the TNFi class, switching from one TNFi drug (etanercept/Enbrel, adalimumab/Humira, infliximab/Remicade, certolizumab pegol/Cimzia, and golimumab/Simponi) to another.

One year later, there didn’t seem to be much difference between those who had switched to a second (or third) TNFi and those who had gone on to a drug in another class in terms of the number of people who reached low disease activity.

“In this real-world analysis of patients with RA starting a new [non] TNFi or TNFi biologic after prior exposure to one or more TNFi therapies, we found no significant difference between either treatment option,” the authors wrote. “Numeric trends somewhat favored an [non] TNFi, particularly in the subgroup of patients with two or more prior TNFi therapies and for those receiving biologic monotherapy, but despite the large sample size of this cohort, none were significant.”

Bottom line: There are still no clear answers, so you and your doctor may have to make your best guess about the next treatment to try when your first biologic isn’t working well enough to control your RA symptoms.

Found This Study Interesting? Get Involved

If you are diagnosed with arthritis or another musculoskeletal condition, we encourage you to participate in future studies by joining CreakyJoints’ patient research registry, ArthritisPower. ArthritisPower is the first-ever patient-led, patient-centered research registry for joint, bone, and inflammatory skin conditions. Learn more and sign up here.

Curtis JR, et al. TNFi Cycling Versus Changing Mechanism of Action in TNFi-Experienced Patients: Result of the Corrona CERTAIN Comparative Effectiveness Study. ACR Open Rheumatology. November 5, 2021. doi:

Fraenkel L, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care & Research. July 2021. doi:

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