RA Remission: Flare Risk Observed With TNF Inhibitor Reduction After 1 Year

Among patients with rheumatoid arthritis (RA) in remission for at least one year with continuous tumor necrosis factor (TNF) inhibitor usage, a rise in flare occurrence was observed among those who gradually reduced TNF inhibitor use until cessation. The majority of these patients achieved remission again following the resumption of full-dose treatment, according to study results published in Annals of the Rheumatic Disease.

Researchers explored the impact of tapering TNF inhibitor therapy until discontinuation vs maintaining stable treatment on the risk for disease activity flares among patients with RA in clinical remission for at least one year.

The randomized, open-label, noninferiority Remission in Rheumatoid Arthritis – Assessing Withdrawal of Disease-modifying Antirheumatic Drugs in a Non-inferiority Design (ARCTIC REWIND; ClinicalTrials.gov Identifier: NCT01881308) trial was conducted at multiple rheumatology centers in Norway. Patients aged 18 to 80 years with confirmed RA who were in remission for at least one year were included in the analysis.

Patients were randomly assigned 1:1 to continued stable TNF inhibitor treatment or to tapered treatment, with the TNF inhibitor dose reduced to half for 4 months until being withdrawn entirely at the patient’s 4-month visit, provided the patient remained in remission. The primary efficacy endpoint was the percentage of patients who experienced a disease flare within 12 months from baseline.

Remission was defined by a Disease Activity Score (DAS) less than 1.6. A disease flare was defined as having a combination of a DAS score greater than 1.6, an increase in DAS score of at least 0.6 points from the previous visit, and at least 2 swollen joints out of the 44 examined.

In the final analysis, a total of 92 patients received treatment, with 4 patients from each treatment group being excluded from the per-protocol data set. The per-protocol population was comprised of 84 patients, with 41 patients allocated to the stable treatment group and 43 patients included in the TNF inhibitor tapering group.

Of the individuals in the TNF inhibitor tapering group, 63% (n=27/43) experienced a flare within a span of 12 months. Among the stable treatment group, only 5% (n=2/41) experienced a flare within the 12-month period (P <.0001).

The risk difference between both groups was 58% (95% CI, 42%-74%). The lower limit of the confidence interval exceeded the noninferiority margin, signifying that noninferiority was not established.

Among the TNF inhibitor tapering group, 3 patients (6%) experienced a serious adverse event, including one viral infection, compared with 2 patients (4%) in the stable treatment group. No malignancies or fatalities were reported.

The most common adverse event among both groups was upper respiratory tract infection, as reported by 5 patients in the TNF inhibitor tapering group and 14 patients in the stable treatment group.

This study was limited by the open label design, which could potentially influence flare assessment.

The study authors stated, “Our findings show that the risk of experiencing a flare if [TNF inhibitor] is tapered to discontinuation is significant even in prolonged remission, but that most patients regain remission when the initial dose is started again.”

“The results may support shared treatment decisions between clinicians and the growing group of patients with RA who attain sustained remission using a [TNF inhibitor],” they concluded.

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Rheumatology Advisor