Support for TNF inhibitor dose reduction in RA patients with low disease activity
medwireNews: Dose reduction of tumor necrosis factor (TNF) inhibitors may be an appropriate strategy for rheumatoid arthritis (RA) patients who achieve low disease activity while receiving full doses of the agents, report the authors of a Cochrane systematic review.
Lise Verhoef (Sint Maartenskliniek, Nijmegen, the Netherlands) and colleagues caution, however, “that all treatment changes in RA should be done carefully on a background of ‘treat to target’, that is guided by disease activity.”
The systematic review – an update of a similar review conducted in 2014 – included 13 randomized controlled trials and one controlled clinical trial investigating dose reduction, disease activity-guided tapering, or discontinuation among patients receiving TNF inhibitors, primarily adalimumab and etanercept. The average age of patients was between 47 and 60 years, and trial duration ranged from 6 months to 3.5 years.
In the six studies evaluating fixed-dose reduction of TNF inhibitors after at least 3–12 months of stable low disease activity, the researchers say that dose reduction was “comparable to continuation of the standard dose regarding disease activity and function.”
Indeed, the average DAS28 score after 26–52 weeks of follow-up was similar among patients in the dose reduction versus continuation group, at 2.40 and 2.34, respectively. HAQ-DI scores were also comparable between the groups, at an average of 0.61 and 0.52, respectively, on a scale of 0–3 where a higher score indicates worse physical function.
Verhoef et al say that fixed-dose reduction of TNF inhibitors “probably slightly increases” the risk for experiencing minimal radiographic progression after 1 year, with rates of 129 and 105 per 1000 patients for the dose reduction and continuation groups, respectively.
In accordance with the results for fixed-dose reductions, the team found that disease activity-guided tapering of the TNF inhibitor dose resulted in “little or no difference” in average disease activity relative to treatment continuation, but “may slightly increase” the proportion of patients experiencing minimal radiographic progression. These findings were based on the results of three studies.
“Because disease activity-guided dose tapering provides the opportunity to find the lowest effective dose for each individual patient and to discontinue treatment as the final step of the tapering process, this may be the most cost-effective and feasible approach in clinical practice,” write Verhoef and colleagues in The Cochrane Library.
However, they stress that based on the results of eight studies, complete discontinuation of TNF inhibitors in the absence of disease activity-guided adaptation “is probably inferior to continuation of treatment” in terms of disease activity, the proportion of patients in remission, and minimal radiographic progression.
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