RA patients in remission should continue taking TNF inhibitors to prevent flare-ups, the study found

New research at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR), found that patients with rheumatoid arthritis (RA) in sustained remission who stopped taking TNF inhibitors (TNFi) had significantly more flares and lower Boolean 2.0 remission rates compared to those who continued treatment. Boolean 2.0 is a revised definition for evaluating disease activity in RA, classifying more patients as achieving remission than Boolean 1.0. It is endorsed by the American College of Rheumatology and the European Alliance for Associations in Rheumatology (EULAR) (Abstract #L07).

As more RA patients achieve durable remission, questions remain about the long-term effectiveness of tapering and stopping TNFi treatment. In the randomized, multicenter, noninferiority ARCTIC REWIND trial, Siri Lillegraven, MD, MPH, PhD at Diakonhjemmet Hospital, Oslo, Norway, and colleagues compared the three-year effect of tapering versus stable treatment in RA patients in sustained remission. It follows a trial last year.

The current study included 92 patients from Norwegian rheumatology centers who were randomized 1:1 to taper off TNF inhibitors until discontinuation or continuation of treatment. During the three-year study period, all received study visits every four months. Patients restarted treatment at the full dose if they experienced a flare, which was defined as loss of remission plus an increase in disease activity score of 0.6 units or more and two or more swollen joints. In lieu of these criteria, a doctor and a patient might agree that a significant flare had occurred. The study also looked at remission status, medication use and serious side effects or complications.

Of the original 92 patients, 80 (87%) completed three-year follow-up. At the end of the study, 75% of patients in the tapering group experienced a flare, compared to 15% in the stable group. Most of those who experienced a flare were in remission by their next office visit (81% in the taper group and 67% in the stable group), although the taper group had significantly lower Boolean 2.0 remission rates throughout the study.

Lillegraven says the researchers were “somewhat surprised by the difference in the proportion of patients in ACR/EULAR Boolean remission in the two groups,” noting that “although most patients in the taper group experienced a flare within the first year and the earlier resume treatment at full dose Boolean 2.0 remission rates were significantly lower in the tapering TNFi group than in the stable group throughout the study period.”

The risk difference for flares observed in this data [-24% over three years] is quite similar to what was observed in the one-year study. That’s a bit surprising, because we might have expected that more patients receiving stable treatment would develop a flare over time, narrowing the difference between the two groups.”

Siri Lillegraven, MD, MPH, PhD at Diakonhjemmet Hospital, Oslo, Norway

Lillegraven notes that the study’s open-label design could influence the evaluation of flares, but says that study staff “were continuously instructed on the importance of recording flares similarly in both groups, a pragmatic approach that will improve clinical care reflects, where patients know which treatment they are receiving. received.”

Lillegraven says her team has many studies planned to better understand how to personalize treatment for RA patients in remission. This includes factors that can help determine which patients should and should not taper off their treatment.

“We have begun planning a 10-year follow-up of the study to better understand the long-term outcomes of different treatment strategies in RA remission. We are [also] consider studies to better understand patient preferences regarding medication tapering.”

Shared decision-making is central to any consideration of tapering, she says.

“The patient should be informed of the risks and benefits of tapering, and the patient’s overall situation should be taken into account before the decision is made. Although the data do not support tapering off TNFi at a group level, factors such as side effects related to the treatment or the patient having a strong preference for tapering will obviously influence such a decision.”