Quantifying Disease Flares After Discontinuing TNFis in Stable RA

Patients randomized to discontinuing TNFis were at increased risk of experiencing a disease flare within 12 months.

Among patients with rheumatoid arthritis (RA) in remission or with stable low disease activity, discontinuing treatment with a tumor necrosis factor inhibitor (TNFi) resulted in more disease flares in many patients at the 12-month mark as compared to those who continued TNFi treatment. These results were recently published in Arthritis & Rheumatology.

Observational studies suggest that in RA patients with stable low disease activity, TNFi treatment may discontinued without resurgence in disease activity. Marjan Ghiti Moghadam, MD, from the University of Twente in the Netherlands, and colleagues examined whether TNFi treatment may be safely stopped in patients with established RA in remission or with stable low disease activity (defined by Disease Activity Score in 28 joints [DAS28] <3.2 over 6 months) who had received TNFi treatment for at least 1 year.

A total of 817 study participants who met definitions of remission or low disease activity were randomized 2:1 to either stop TNFi treatment or continue TNFi treatment. Disease flare was defined as a DAS28 of ≥3.2 within 12 months plus an increase in DAS28 score by ≥0.6 from baseline.

High Yield Data Summary

  • Patients with low RA disease activity who discontinued TNFi treatment had >3-fold increased risk of having a flare within 12 months as compared to those who continued TNFi therapy

The RA flare rate at 12 months was significantly higher among patients who stopped TNFi treatment than among those who continued treatment (51.2% vs 18.2%; hazard ratio, 3.50; 95% confidence interval, 2.60 to 4.72; P < .001). 

Patients in the stop group also had a higher mean DAS28 than those in the continuation group (P < .001).

A total of 195 patients in the stop group experienced a flare and restarted TNFi treatment within 26 weeks after stopping treatment. The majority (84.6%) regained low disease activity (DAS28 <3.2) within 6 months after restarting treatment, with a median time to low disease activity of 12 weeks. 

Hospitalizations were also more common among patients who stopped treatment (6.4%) than among those who continued treatment (2.4%), although most instances were not considered to be intervention-related.

“Although patients in the TNFi stop group were clearly at increased risk of experiencing a flare within 12 months, the finding that even among patients with established RA, almost one-half were able to stop their TNFi treatment could be considered a promising result,” the authors noted.

Summary and Clinical Applicability

Researchers of this randomized, controlled, open-label study found that when patients with established RA in remission or with stable low disease activity stopped TNFi treatment, they had more flares and higher overall disease activity at 12 months when compared with patients who continued TNFi treatment.

Restarting treatment quickly and effectively regained low disease activity among most patients in the stop group who experienced a flare.

“In conclusion, this study showed that stopping treatment with TNFi in RA patients whose disease is in remission or who have stable low disease activity results in substantially more flares than does continuation of TNFi treatment,” the authors wrote.

Limitations and Disclosures

  • Study design was open-label, which may have introduced bias in disease activity assessments and treatment decisions
  • Study follow-up time of 12 months may not be long enough to evaluate the long-term effects of stopping TNFi treatment
  • Study only examined RA flare rates after complete TNFi discontinuation, TNFi dose reduction may have resulted in less flare rates while significantly reducing risk of medication adverse effects

This study was funded by The Netherlands Organization for Health Research and Development (ZonMw) and the Government of The Netherlands, Ministry of Health, Welfare, and Sport. The authors report no relevant disclosures. 

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Ghiti Moghadam M, Vonkeman HE, Ten Klooster PM, et al; Dutch National POET Collaboration. Stopping tumor necrosis factor inhibitor treatment in patients with established rheumatoid arthritis in remission or with stable low disease activity: A pragmatic multicenter, open-label randomized controlled trial.  Arthritis Rheumatol. 2016;68(8):1810-7.

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