Early Anti-TNF Therapy Shown to Prevent Difficult-to-Treat RA

Study finds first-line use of TNF inhibitors in early RA significantly reduces risk of developing difficult-to-treat disease.

Mar. 12, 2026 at 9:24am

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A study from the University of Leeds found that using a TNF inhibitor as first-line therapy in early rheumatoid arthritis (RA) was associated with a significantly lower rate of difficult-to-treat (D2T) RA at 5 years compared to usual care with conventional DMARDs. The findings suggest that early use of TNF inhibitors could help prevent the development of treatment-resistant RA, which has become a major challenge in managing the disease.

Why it matters

Difficult-to-treat RA is a growing concern, as it requires more intensive and costly treatments. This study indicates that using the most effective therapies upfront, rather than a step-wise approach, may be a more effective strategy to avoid this treatment-resistant state. The availability of more affordable TNF inhibitor biosimilars has also made this approach more economically viable, potentially allowing for wider adoption.

The details

Researchers at the University of Leeds identified patients with early RA who were treated with a TNF inhibitor as first-line therapy for 12 months, and compared them to a control group receiving standard care with conventional DMARDs. At 5 years, only 0.9% of the TNF inhibitor group met the criteria for D2T RA, compared to 7% in the control group. The TNF inhibitor group also had higher rates of drug-free remission. While the difference was no longer statistically significant at 10 years, the TNF inhibitor group still required fewer biologic DMARDs over that time period.

  • The study findings were first presented at the American College of Rheumatology 2025 Annual Meeting.
  • The researchers are currently analyzing data from the recently completed TEEMS clinical trial, which assessed the use of stratified first-line TNF inhibitor therapy in early RA patients based on CD4 T-cell subset frequency.

The players

Jack Cush, MD

A professor at the Anne Burnett Marion School of Medicine at Texas Christian University in Fort Worth, Texas, and the editor of RheumNow.com.

Kulveer Mankia, BMBCh, DM

The senior investigator on the study and a professor of clinical and translational rheumatology at the University of Leeds.

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What they’re saying

“Difficult-to-treat disease is our Achilles heel. Early TNF inhibition produced an advantage [in this cohort analysis], especially when it came to reducing the number who went on to develop difficult-to-treat RA. The study makes the case for, 'use your best drug first.'”

— Jack Cush, MD

“The concept is, why don't we use a better up-front strategy with a well-established safety profile, which is now more economically attractive and that patients would much rather have, and doctors would much rather prescribe?”

— Kulveer Mankia, BMBCh, DM, Professor of Clinical and Translational Rheumatology, University of Leeds

What’s next

Discussions are underway at NHS England about potentially shifting guidance to allow for more routine use of first-line TNF inhibitor therapy, especially in early RA patients with a poorer prognosis. The researchers are also planning to present findings from the TEEMS trial, which looked at stratifying first-line TNF inhibitor use based on CD4 T-cell subset frequency, at the EULAR 2026 meeting.

The takeaway

This study provides strong evidence that using the most effective therapies like TNF inhibitors as first-line treatment for early RA, rather than a step-wise approach, can significantly reduce the risk of developing difficult-to-treat disease. With the availability of more affordable biosimilars and the high cost of managing treatment-resistant RA, this strategy could become more widely adopted, leading to better long-term outcomes for RA patients.