Medicines

TDM and dose reductions won’t benefit all patients but worth it for some


Optimising treatment dosing for inflammatory disorders such as RA is as complex as the disorders themselves, new research from Norway has shown.

In one RA study trialling a 50% dose reduction of csDMARDs versus standard dosing in RA patients in remission, researchers found a significant increase in flares over 12 months in the half-dose group.

At least one disease flare occurred during the year in 25% of patients in the half-dose group compared to 6% in the stable dose group (p= 0.003).

However the ARCTIC REWIND study, published in JAMA, found rates of DAS remission were similar in the two groups (85% v 92%) at 12 months.

“Individual measures of disease activity, composite disease activity scores, and the number of patients in remission according to different criteria were not significantly different in the 2 groups over the 12months. This was also true for functional and ultrasound outcomes,” the study said.

The number of adverse events were numerically lower in the half-dose group (54 v 75 events) and were typically mild infections in both groups.

The study concluded the findings did not support treatment with half-dose therapy.

However an editorial in the journal flipped the findings on their head and said 75% of patients reduced therapy and remained in remission.

“When flares occurred, they were typically mild. Most patients had low disease activity, and remission was regained after medication doses were increased.”

“Based on results from this trial, attempting dose reduction for patients in remission may be reasonable for some patients. While the ARCTIC REWIND study does not support mandatory reduction in csDMARDs for all patients in remission, it 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.”

The editorial also commented on a second study – the Norwegian Drug Monitoring Trial (NOR-DRUM) trial, which was reported in the limbic late last year.

Now published in JAMA, NOR-DRUM found dose adjustment of infliximab with therapeutic drug monitoring (TDM) made no difference to clinical outcomes in patients with a variety of inflammatory conditions including RA, psoriatic arthritis and axial spondyloarthritis.

The editorial said prescribing biologics was complicated and there were many possible explanations why TDM failed to demonstrate benefit.

“While this trial convincingly demonstrated that in a mixed disease indication population, implementing TDM at time of initial induction therapy provided little benefit, it does not rule out potential benefit for patients at high risk for developing [antidrug antibodies] ADAs.”

“Patients with RA, those not receiving concomitant immunosuppression, those who developed ADAs against other (noninfliximab) monoclonal antibodies, and those with a loss of response (ie, “reactive” TDM on a case-specific basis, rather than “proactive” TDM in everyone), might still benefit from TDM.”

They concluded that TDM in biologic therapy or routine dose reduction of csDMARDs might not benefit everyone.

“However, a subset of patients may benefit from these therapeutic approaches. Methodologic approaches, such as adaptive (eg, SMART) trials, may identify characteristics of patients most likely to benefit from individualised strategies.”

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