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INT-011 Randomised controlled non-inferiority study of disease activity guided dose reduction and withdrawal of adalimumab and etanercept compared to usual care in rheumatoid arthritis


Background TNF inhibitors (TNFi) have proven to be effective in the treatment of rheumatoid arthritis (RA). They are however associated with side effects and high costs, making dose reduction or discontinuation an attractive option.

Purpose This study aims to evaluate whether a disease activity guided dose reduction strategy of adalimumab or etanercept (TNFi) is non inferior in maintaining disease control in patients with RA compared to usual care.

Materials and methods Patients with RA and low disease activity using adalimumab or etanercept were randomised 2:1 to a dose reduction strategy or usual care. The TNFi dose reduction strategy consisted of increasing the interval between injections every 3 months until flare or discontinuation. In case of flare, the TNFi could be restarted or interval shortened. The primary outcome was the difference in proportions of patients with persistent flare between the two groups compared against a non-inferiority (NI) margin of 20%.

Results Dose reduction was non-inferior to usual care (12% and 10%; difference = 2% in major flare, 95% confidence interval (CI) -12 to 12). TNFi could successfully be stopped in 20% (95% CI 13 to 28) of patients, the interval successfully increased in 43% (95% CI 34 to 53). In 37% (95% CI 28 to 46) of patients no dose reduction was possible. Functional status, quality of life and relevant radiographic progression and adverse events were not different between the groups, although short lived flares (73 vs 27%) and minimal radiographic progression (32 vs 15%) were more frequent in the dose reduction group.

Conclusion Disease activity guided TNFi dose reduction strategy is non-inferior to usual care with regard to major flaring, while resulting in successful dose reduction or stopping in two third of the patients.

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