Reduced prescription of TNF-inhibitors in chronic arthritis based on therapeutic drug monitoring: A randomized controlled trial

Abstract

Objective Dosing of tumour necrosis factor-α inhibitors (TNFis) is not personalized causing interindividual variation in serum drug levels; however, dose optimization is not widely implemented. We hypothesized that some patients areoverdosed; thus, drug prescription could be reduced by therapeutic drugmonitoring (TDM). Method Independent of disease activity, 239 adults treated for rheumatoid arthritis (n = 99), psoriatic arthritis 15 (n = 48), or spondyloarthritis (n = 92) were recruited for a 48-week prospective, randomized open-label trial. Standard care alone or plusTDM was applied in chronic arthritis patients treated with infliximab (IFX), (n= 81), etanercept (ETN) (n = 79), or adalimumab (ADA) (n = 79). Serum TNFitrough levels assessed at inclusion and every 4 months determined patientswithin/outside predefined therapeutic intervals, supporting change inprescription or drug switch. The primary endpoint was reduced drugprescription. Results Compared to standard care, TDM reduced prescribed IFX [−12% (95% confidence interval −20, −3); p = 0.001] and ETN (−15% (−29, 1); p = 0.01], and prolonged the interdosing intervals of ETN [+235% (38, 432); p = 0.02] and ADA [+28% (6, 51); p = 0.04]. Time to drug switch was accelerated (χ2 = 6.03, p = 0.01). No group differences in adverse events, disease activity, or self-reported outcomes were shown, indicating equally sustained remission. Conclusions TDM reduced prescription of IFX, ETN, and ADA and identified patients benefiting from accelerated drug switch, thereby minimizing treatment failure, risk of toxicity, and unnecessary adverse events.