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Anti-TNF withdrawal in rheumatoid arthritis

back of a womanA recent study suggest that the risk of a flare increased by more than three-fold over 1 year when patients in remission, or with stable low disease activity, from rheumatoid arthritis (RA) stopped their anti-tumor necrosis factor (TNF) treatment. The study had 816 patients who had used a TNF inhibitor for at least 1 year and stable doses of conventional disease-modifying anti-rheumatic drugs for at least 6 months.

In the study, a patient’s remission was defined as a disease activity score in 28 joints (DAS28) below 6.2, or had a low disease activity (a DAS28 below 3.2), for at least 6 months. Participants were also considered stable based on rheumatologists’ clinical impression in combination with a baseline DAS28 below 3.2 and at least one C-reactive protein (CRP) level below 10 mg/L in the 6 months prior. A flare was a DAS28 score of 3.2 or higher with an increase of 0.6 or more compared with the baseline DAS28. Participant’s mean age was 60, with mean disease duration of 12 years.

Other findings from the study were:

  • Adalimumab and etanercept were the most common anti-TNF medication being used.
  • More than 80% of the participants were also taking methotrexate
  • Close to two-thirds of the participants had erosive disease.
  • For patients who stopped their TNF inhibitor, the proportion that experienced a flare within 12 months was similar between the group that was included based on available DAS28 scores compared with those that were included based on the rheumatologists’ clinical impression plus CRP.

The authors of the study noted: “Of the 195 patients who restarted a TNF inhibitor after a flare during the first 6 months, 67.7% again were in clinical remission and another 16.9% had low disease activity within 26 weeks. The median time to regaining low disease activity was 12 weeks, and 14 weeks for remission. The stop group experienced more hospitalizations than the continuation group (6.4% versus 2.4%, P = 0.012), but there were no notable safety issues associated with stopping and restarting TNF inhibitors.”

Though the results are promising, Eric Matteson, chair of the rheumatology at the Mayo Clinic in Rochester, cautioned that the importance of the study lies in the revelation that most RA patients will have recurrent disease activity after stopping therapy, even in patients who achieve remission or very low disease activity. In an interview with MedPage Today, he added: “In my view, RA is a chronic disease, which like hypertension, requires chronic, and for most patients, lifelong therapy.”