Personalized dose reduction based on serum TNF-inhibitors concentration
do not lead to changes in disease activity in chronic arthritis: A
randomized controlled trial
Abstract
OBJECTIVES: We hypothesized that Therapeutic Drug Monitoring (TDM)
decreased drug consumption or accelerated switch of biologics in chronic
arthritis patients undergoing TNF-alpha inhibiting (TNFi)-therapy.
Primary outcome was dose reduction, secondary outcomes included clinical
scores DAS28-CRP or ASDAS-CRP, self-reported outcome and experienced
adverse events. METHODS: 48-week prospective, randomized open-label
trial investigating TDM in participants (n=239) treated with infliximab
(IFX), etanercept (ETN) or adalimumab (ADA), receiving standard of care
or standard of care plus TDM, the latter based on serum-trough
concentration measurements of IFX, ETN and ADA. Independent of clinical
status, adults treated for their rheumatoid arthritis (41%), psoriatic
arthritis (20%), or spondylarthritis (39%), were included in a
tertiary outpatient clinic. Serum TNFi trough-values were determined at
inclusion and every 16 weeks and used proactively in the TDM-group to
evaluate whether participants were within the therapeutic window or not,
consequently leading to maintained TNFi-therapy, dose-reduction, or
switch to other biologics. RESULTS: In comparison to standard of care,
TDM reduced doses for IFX (- 12% [CI: -20; -3] p=0.001); ETN (-15
% [-29; 1]; p=0.01) and prolonged the inter-dosing interval in ETN
(+ 235 %;[38;432] p=0.02) and ADA (+ 28%;[6; 51] p = 0.04) and
accelerated switch of biologics (χ2= 6.03, p=0.01). No group-differences
were shown in clinical assessment CRP, DAS28-CRP or ASDAS-CRP, nor in
self-reported outcome or experienced adverse events, indicating
sustained disease control. • CONCLUSIONS – TDM improved clinical
decision making and caused earlier and targeted dose-reduction and
accelerated switch of biologics, thereby preventing over- and under
medication.