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12-05-2021 | Rheumatology | News | Article

NOR-DRUM, ARCTIC REWIND trials evaluate tailored DMARD strategies

Claire Barnard

medwireNews: Findings from two Norwegian trials published in JAMA do not support routine therapeutic drug monitoring (TDM) with biologics or dose reduction of conventional DMARDs in patients with inflammatory diseases.

In the first trial, the NOR-DRUM investigators evaluated TDM – a strategy involving measurement of serum drug levels and antidrug antibodies (ADAs) followed by adjustment of drug doses when needed – in 398 patients with rheumatic diseases, inflammatory bowel disease, or psoriasis who were initiating treatment with the tumor necrosis factor (TNF) inhibitor infliximab.

As reported previously by medwireNews, Silje Watterdal Syversen (Diakonhjemmet Hospital, Oslo, Norway) and co-investigators found that rates of clinical remission at week 30 were comparable among participants randomly assigned to receive infliximab with TDM and those given standard infliximab treatment, leading them to conclude that routine TDM use is not warranted in this patient population.

Writing in a commentary accompanying the trial publications, Jeffrey Curtis (University of Alabama at Birmingham, USA) and colleagues say that “there are many possible explanations” for why TDM was not better than standard care in the NOR-DRUM study.

They speculate “that TDM is effective only in specific subgroups,” and point out that only a quarter of participants in the intervention group required dose adjustment, suggesting most patients did not need TDM. Moreover, “it remains unclear whether published therapeutic ranges for serum drug levels represent the optimal target for all patients,” they add.

Curtis and co-authors say that while NOR-DRUM “convincingly” demonstrates little benefit of implementing TDM at the time of biologic initiation in a mixed population, “it does not rule out potential benefit for patients at high risk for developing ADAs.”

The second study, ARCTIC REWIND, included two randomized controlled trials of treatment reduction – one for TNF inhibitors and one for conventional DMARDs – in rheumatoid arthritis (RA) patients in sustained remission. The previously reported TNF inhibitor trial showed that a tapering strategy led to an increased flare risk compared with TNF inhibitor continuation.

In the present analysis, the ARCTIC REWIND investigators assessed the impact of dose reduction versus standard-dose treatment in 155 RA patients taking conventional DMARDs who had been in remission for at least 1 year at baseline. The most commonly used DMARD was oral methotrexate, taken by approximately 65% of participants.

Siri Lillegraven (Diakonhjemmet Hospital) and co-authors report that the difference in flare rates between the 77 patients who were randomly assigned to receive half-dose DMARDs and the 78 patients who continued with the same DMARD dose did not meet the criteria for noninferiority. During 1 year of follow-up, 25% of participants in the dose-reduction group and 6% of those in the control group experienced flares, a significant difference.

“These findings do not support treatment with half-dose therapy,” write the researchers.

Curtis and fellow commentators agree that “the ARCTIC REWIND study does not support mandatory reduction in [conventional] DMARDs for all patients in remission,” but they suggest that dose reduction “may be reasonable for some patients,” given that three-quarters of those in the half-dose group remained in remission at 1 year.

They add that ARCTIC REWIND “provides some evidence to guide discussions of dose reductions for patients who have adverse drug effects or who have other reasons to reduce immunomodulatory treatment.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA 2021; 325: 1744–1754
JAMA 2021; 325: 1755–1764
JAMA 2021; 325: 1726–1728

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