In adults with rheumatoid arthritis, which disease‐modifying antirheumatic medicines (DMARDs) (a type of medication that stops or slows the disease process) work after a biologic or targeted synthetic DMARD has failed?

Key messages

• Several medications can help rheumatoid arthritis symptoms after failure of a biologic or targeted synthetic (b/ts) disease‐modifying antirheumatic medicine (DMARD) (a type of medication that stops or slows the disease process).

• We are unsure how the medications compare with placebo (dummy treatment) or with each other in terms of unwanted effects.

• We need more studies that directly compare drugs to get a better idea of which is best. Treatment decisions should consider individual health factors and preferences.

What is rheumatoid arthritis?

Rheumatoid arthritis is a disease where the body’s immune system, which normally fights infections, mistakenly attacks the joints. This causes joint pain, swelling, stiffness, and disability. Rheumatoid arthritis is a long-term condition, but treatments can help manage symptoms and slow the damage.

How is rheumatoid arthritis treated?

Rheumatoid arthritis is typically treated with disease-modifying antirheumatic drugs (DMARDs), which work to control the inflammation responsible for symptoms and also prevent joint damage. There are various kinds of DMARDS. Targeted synthetic (ts) DMARDs work by targeting specific cells or proteins. Biologic (b) DMARDs also target specific cells or proteins, but are made from material that comes from living organisms. Lastly, conventional synthetic DMARDs affect the whole immune system rather than targeting specific parts of it.

What did we want to find out?

We wanted to explore the effectiveness of DMARDs in adults with rheumatoid arthritis for whom treatment with a b/ts DMARD didn't work. This is a 'living' systematic review, meaning that it will be updated regularly. As this field of medicine is always growing and changing, we want to have the most up-to-date evidence reflected in this review.

What did we do?

We searched for studies that tested the effectiveness of DMARDs in adults with rheumatoid arthritis for whom treatment with one b/ts DMARD didn't work.

We looked at how well the available DMARDs reduced the symptoms of rheumatoid arthritis, including pain, joint swelling, and issues with joint movement. We measured this using the American College of Rheumatology 50% response criteria, or ACR50 response. An ACR50 response means the rheumatoid arthritis medication is effective and symptoms have improved by at least half. We also looked at any unwanted effect that might cause a person to stop using the medication.

We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.

What did we find?

We found 19 studies that involved 4779 people with rheumatoid arthritis who had tried a tumour necrosis factor inhibitor (a type of bDMARD) in the past, but it did not improve their symptoms. Most people in these studies were women, with an average age of 49 to 58 years, who had been living with rheumatoid arthritis for an average of 6 to 14 years. The studies were conducted worldwide, including in North America, Europe, and Asia. Nine studies were funded by pharmaceutical companies, while the other 10 were funded by national research grants.

Several medications reduced the symptoms of rheumatoid arthritis in patients who have failed a b/ts DMARD:

• a different tumour necrosis factor inhibitor (2 studies; 343 people);

• sarilumab (1 study, 365 people);

• tocilizumab 4 mg/kg (1 study, 319 people);

• tocilizumab 8 mg/kg (1 study, 328 people);

• intravenous (into a vein) abatacept (2 studies, 665 people);

• rituximab (1 study, 499 people);

• upadacitinib (1 study, 333 people);

• tofacitinib (1 study, 263 people);

• a higher dose of baricitinib (1 study, 353 people).

We are unsure how the medications compare with placebo (dummy treatment) or with each other in terms of unwanted effects, as the evidence for this outcome was generally of low quality.

What are the limitations of the evidence?

Our confidence in the evidence varied from high to very low. In cases where our confidence was limited, this was because there were not enough studies to be certain about the results. When we searched for studies to include in the review, we found some gaps in the available evidence. Specifically, we found that there were fewer studies that directly compared medications with each other and more studies that compared medications to a placebo. More studies that compare drugs directly would better help us understand which drug is best.

How up to date is this evidence?

The evidence is current to 28 November 2025. As this is a living review, we will be updating this research yearly to ensure our results reflect new evidence.