Is Your Rheumatoid Arthritis Not Responding to Treatment?

Sometimes it’s trial and error to find a new treatment that works best for you.

Medically reviewed in April 2022

If you have rheumatoid arthritis (RA), you may know firsthand that finding the right treatment can sometimes be challenging, particularly if you have moderate-to-severe disease activity. 

Fortunately, there are numerous effective treatments for RA. Most patients take one or more disease-modifying antirheumatic drugs, or DMARDs. Methotrexate, for example, which can be taken orally or by subcutaneous injection, is a first-line treatment for most RA patients, either alone or in combination with other treatments. 

TNF-inhibitors (also called anti-TNF drugs) block a protein called TNF (tumor necrosis factor), which promotes inflammation. Patients can take one or more TNF-inhibitors, alone or in combination with methotrexate. Other oral and injectable biologic medications target different inflammatory-causing proteins. Biologics can be especially helpful in reducing inflammation and limiting damage in the joints affected by RA. 

When your rheumatoid arthritis is not responding to treatment anymore  
“Sometimes, treatments work in the beginning and then lose efficacy [effectiveness] or the efficacy wanes over time,” explains  Petros Efthimiou, MD , a clinical professor of medicine and rheumatologist at NYU Langone Health. 

It’s a challenge, he says, when the same medicine that worked great in the beginning, doesn’t work as well after a year or two. This can be particularly true with biologics. The body sometimes sees the drug as a foreign object and mounts an immune response against it by developing antibodies (proteins that responds to pathogens). “It’s not uncommon for neutralizing antibodies to limit the efficacy of the drug and change its pharmacodynamic properties [what the drug does to the body],” Dr. Efthimiou says. 

As a result, patients start seeing an increase in local injection site reactions and a decrease in effectiveness. “This loss of efficacy can be particularly troublesome because patients experience more pain, more swelling, more arthritic complaints,” Dr. Efthimiou says. Patients also notice that a dose of medication doesn’t last as long as it used to. 

Dr. Efthimiou says patients have options. “We can change the frequency of administration, or switch to a different agent.” 

It’s common for TNF-inhibitors to start losing efficacy after a year or two of administration (it happens in about one-third of patients). However, about 30 to 40 percent of patients who fail on one TNF medication do well when they switch to a different TNF drug. Although the drugs target the same protein (TNF), there are small differences that can make one more effective for a patient than another. An alternative TNF-inhibitor may also not develop drug-neutralizing antibodies. 

Another strategy to try when your TNF-inhibitor stops working is to switch to a completely different biologic drug (often in combination with methotrexate) that doesn’t target TNF, particularly when the TNF drug doesn’t work from the start. About 60 percent of people who fail an anti-TNF drug have good or moderate response on a different biologic. 

The American College of Rheumatology (ACR) provides detailed treatment recommendations for RA, depending on a patient’s disease activity and how long they’ve had RA. For example, for patients with high disease activity despite DMARD therapy, it recommends a combination of a DMARD or a TNF-inhibitor or a non-TNF biologic, with or without methotrexate, instead of one DMARD or one TNF-inhibitor alone. It also recommends administering a biologic therapy with methotrexate because the combination is more effective than a biologic treatment alone. 

Dr. Efthimiou says the ACRs guidelines are flexible enough to allow doctors to tailor treatments for individual patients according to their type of disease, how severe it is, if the patient has any co-existing conditions, the patient’s preferences for injectable versus oral treatments and what the patient’s insurance company will cover. 

When treatment fails, it can cause anxiety, says Dr. Efthimiou. Patients have symptoms again and it affects their quality of life. 

Try not to panic if your treatment stops working. With all the medication options available, Dr. Efthimiou says the number of RA patients who don’t respond to any available treatments is shrinking. Still, he says, an initial response is not a guarantee that a treatment will last for a lifetime or even a very long time. 

Tell your doctor immediately if your rheumatoid arthritis is no longer responding to treatment. It might take a bit of trial and error; however, there’s a good chance your physician will find a drug—or a combination of drugs—that works for you. 

Medically reviewed in April 2020. Updated in February 2021. 

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