Alfons A. den Broeder, Lise M. Verhoef, Jaap Fransen, Rogier Thurlings, Bart J. F. van den Bemt, Steven Teerenstra, Nadine Boers, Nathan den Broeder, Frank H. J. van den Hoogen
Abstract
A standard low-dosing schedule of rituximab (RTX; 2 × 500 mg or 1 × 1000 mg) is as effective for active rheumatoid arthritis (RA) as the registered dose (2 × 1000 mg). Moreover, several small uncontrolled studies suggest that even lower-dosed treatment with RTX also leads to good treatment response in patients with RA. Retreatment with such an 'ultra-low' dose RTX in patients who responded well to RTX induction treatment is of special interest, as long-term use of lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. However, the effect of ultra-low dose of RTX has not been investigated using a controlled trial of proper design and dimensions.
REDO is an investigator driven six-month pragmatic, double-blind, randomised controlled non-inferiority trial on the effects of ultra-low-dose RTX (1 × 500 or 1 × 200 mg) compared to standard low dose (1 × 1000 mg) in RA patients who are being retreated with RTX. A total of 140 RA patients, having reached low disease activity (DAS28CRP < 2.9) after the previous RTX infusion and DAS28CRP < 3.5 at moment of retreatment, are randomised in a ratio of 1:2:2 to 1 × 1000 mg, 1 × 500 mg or 1 × 200 mg. The primary objective is testing non-inferiority of the ultra-low-dose vs. standard low-dose RTX, by comparing mean change in DAS28CRP from baseline to six months to the non-inferiority margin of 0.6. Secondary outcomes over the same period are: function; quality of life; safety; costs; and pharmacokinetics and dynamics as process measures.
This study protocol shares characteristics of both early dose finding trials as well as late pragmatic clinical studies. Several choices in the design of this trial are described and possible consequences for RA treatment and expected biosimilar introduction are discussed.
Dutch Trial Register, NTR6117 . Registered on 15 November 2016 (CMO NL57520.091.16 , 8 November 2016).
Pharmacology, Toxicology and Pharmaceutical Science
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12%
Agricultural and Biological Sciences
3
4%
Biochemistry, Genetics and Molecular Biology
2
3%
Nursing and Health Professions
2
3%
Other
7
9%
Unknown
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49%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 September 2017.
All research outputs
#14,986,068
of 25,988,468 outputs
Outputs from Trials
#991
of 1,868 outputs
Outputs of similar age
#161,426
of 327,973 outputs
Outputs of similar age from Trials
#7
of 11 outputs
Altmetric has tracked 25,988,468 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
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