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Understanding TNF Inhibitor Discontinuation: Why Some People With RA Change Treatment

Written by Torrey Kim
Updated on January 2, 2026


Your treatment journey with rheumatoid arthritis (RA) might not follow a straight path. You may discontinue a medication if it is not helping you meet your goals, you can’t tolerate it, or it stops working over time.1 This may happen with tumor necrosis factor (TNF) inhibitors, which are common biologic DMARDs used to treat RA — up to 40 percent of people with RA stop taking TNF inhibitors for these reasons.1-3

Dr. Siddharth Tambar spoke with myRAteam to explain why some people with RA might stop taking TNF inhibitors and change treatments. Dr. Tambar is a rheumatologist who earned his medical degree from the State University of New York at Syracuse and completed his internal medicine and rheumatology training at Northwestern Memorial Hospital in Chicago. He’s the owner of the Chicago Arthritis and Regenerative Medicine clinic.


“TNF inhibitors are biologic medications that block a protein called tumor necrosis factor, which causes inflammation in people with RA,” Dr. Tambar said. The aim of RA treatment is to reach remission or low disease activity.2 If a specific RA treatment doesn’t help you achieve that goal in about three to six months or it stops working effectively, it may be time to try something else.2,4,5

In remission, rheumatoid arthritis is either minimally active or inactive.3,6 This means you may experience few or no RA symptoms, such as joint pain, swelling, or stiffness.7 However, remission doesn’t mean your RA disappears completely.6 Instead, it means you have a lower risk of joint damage, fewer symptoms, and very low or no signs of RA in your lab tests.7 Treating your RA and getting to remission may also decrease your risk of RA comorbidities (coexisting conditions) like osteoporosis, heart disease, and serious infections.8,9

Your doctor will monitor your RA regularly to see whether your TNF inhibitor is working.6 Below are several reasons it might be time to change your TNF inhibitor treatment.

No Improvement in Disease Activity After 3 to 6 Months

“If you’ve been using a TNF inhibitor and haven’t achieved low disease activity or remission after three to six months, the guidelines suggest altering your treatment regimen,” Dr. Tambar said.3,4,5 “We call this treat to target. In this case, our target is low disease activity or remission. If you’re not hitting that target, it may be time to adjust your treatment plan.”3,5

Less Relief Over Time With a TNF Inhibitor

In some cases, you may initially find symptom relief with a TNF inhibitor, but the drug later stops controlling your symptoms.2 “This could mean the medication is no longer working effectively,” Dr. Tambar said. “You might experience flares with pain, swelling, tenderness, or warmth in previously affected joints.”

Adverse Events

Some people experience adverse events when taking medications. The U.S. Food and Drug Administration (FDA) defines adverse events as “unfavorable or unintended” health effects linked to a medication, therapy, or procedure.10

One study found that experiencing adverse events is the third most common reason for stopping a TNF inhibitor.1

Insurance or Cost Issues

Sometimes people stop taking TNF inhibitors and change medications because of issues with health insurance or the cost of medication.1 You and your doctor should work together and consider these factors when determining your RA treatment plan.3

The American College of Rheumatology (ACR) developed guidelines to help doctors select RA treatments. These guidelines support switching to a drug from a different class if a TNF inhibitor doesn’t work for you.5 Although some individuals may respond to a second TNF inhibitor, several studies show that switching to a drug in a different class may lead to improved clinical outcomes.1,2,11,12 For these reasons, your doctor may suggest a drug from a different class rather than another TNF inhibitor.

“Thankfully, there are many more treatment options today than there were just a decade ago, so if your RA medication isn’t working, there are other paths to help you achieve remission,” Dr. Tambar said.

In closing, Dr. Tambar emphasized the importance of monitoring: “Regular check-ins with your rheumatologist and open conversations where you share detailed symptoms and personal goals are key.”

Everyone living with RA should be monitored frequently by their doctor to ensure that their treatment is working.4-6 During these checkups, your doctor will ask about your symptoms and how you’re feeling.4,5 They’ll also perform an exam, blood tests, and imaging studies to evaluate joint health.7 Based on the results of those evaluations, they’ll share possible treatment recommendations with you.

Talk with your doctor about RA treatment changes and whether switching drugs may help your symptoms. “You and your provider can work together to create a plan that reflects how you’re doing now and what goals you want to reach in the future,” Dr. Tambar said.

References
  1. Wei W, Knapp K, Wang L, et al. Treatment persistence and clinical outcomes of tumor necrosis factor inhibitor cycling or switching to a new mechanism of action therapy: real-world observational study of rheumatoid arthritis patients in the United States with prior tumor necrosis factor inhibitor therapy. Adv Ther. 2017;34(8):1936-1952. doi:10.1007/s12325-017-0578-8
  2. Johnson KJ, Sanchez HN, Schoenbrunner N. Defining response to TNF-inhibitors in rheumatoid arthritis: the negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders. Clin Rheumatol. 2019;38(11):2967-2976. doi:10.1007/s10067-019-04684-1
  3. Taylor PC, Matucci Cerinic M, Alten R, Avouac J, Westhovens R. Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes. Ther Adv Musculoskelet Dis. 2022;14:1759720X221114101. doi:10.1177/1759720X221114101
  4. Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3-18. doi:10.1136/ard-2022-223356
  5. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939. doi:10.1002/acr.24596
  6. Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017;9(10):249-262. doi:10.1177/1759720X17720366
  7. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023-2038. doi:10.1016/S0140-6736(16)30173-8
  8. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-2219. doi:10.1056/NEJMra1004965
  9. Mehta B, Pedro S, Ozen G, et al. Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study. RMD Open. 2019;5(1):e000935. doi:10.1136/rmdopen-2019-000935
  10. Adverse event. National Center for Advancing Translational Sciences. Accessed April 21, 2025. https://toolkit.ncats.nih.gov/glossary/adverse-event/
  11. Migliore A, Pompilio G, Integlia D, Zhuo J, Alemao E. Cycling of tumor necrosis factor inhibitors versus switching to different mechanism of action therapy in rheumatoid arthritis patients with inadequate response to tumor necrosis factor inhibitors: a Bayesian network meta-analysis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211002682. doi:10.1177/1759720X211002682
  12. Gottenberg JE, Brocq O, Perdriger A, et al. Non-TNF-targeted biologic vs a second anti-tnf drug to treat rheumatoid arthritis in patients with insufficient response to a first anti-TNF drug: a randomized clinical trial. JAMA. 2016;316(11):1172-1180. doi:10.1001/jama.2016.13512
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I’m using nicotine patches now. I’ve had amazing results. I stopped methotrexate and will not stop Orencia which has lost its effectiveness. I’ve had RA for 40 years.

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I'm very drug sensitive and my rheumatoid doctor is having issues of finding a medication. I also have a heart condition. So what's next ?

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