Background In clinical practice of patients with rheumatic diseases, the optimization of the biological therapy (BT) is performed by adjusting drug dose according to clinical activity. To help taking accurate treatment decisions, it will be desirable to have complementary objective tools, next to the ones currently used. Since 2010, at the Rheumatology Department of La Paz University Hospital, serum through levels of TNF inhibitors are taken into account, together with the regular tools to asses clinical activity, in order to improve the therapeutic outcomes.
Objectives To analyse the clinical as well as financial impact of the therapeutic drug monitoring (TDM), based on serum trough drug levels, in rheumatoid arthritis (RA) and Spondiloarthritis (SpA) patients in remission or low disease activity.
Methods In an observational study of daily clinical practice, a total of 88 patients (43 RA and 45 SpA), treated with three TNF inhibitors [31 with Infliximab (Ifx), 29 with Adalimumab (Ada) and 28 with Etanercept (Etn)] between 2006-2012, were included. All patients were in remission or low clinical activity (DAS28<3.2 ó BASDAI <4) throughout the 7 years analyzed. In each patient two different time periods were examined, pre- and during- TDM practice (1stP: 2006-2009 and 2ndP: 2010-2012) to observe if serum trough drug levels influence on therapeutic decisions as down-titration or cessation of anti-TNF therapy. Drug levels were measured by capture ELISA´s as described (1,2,3).
Results The mean timespan of disease duration was 17.52 ±9.38 years and the mean in biological therapy was 5.85 ±1.33 years. All patients were clinically active at the beginning of anti-TNF therapy (RA: DAS28 4.34± 1,39 and SpA: BASDAI 5.51 ±1.61). All patients had a stable clinical activity along both time periods [RA (DAS28): 2.51±0.85 in 1st P vs 2.31±0.52 in 2nd P, p=0.061; SpA (BASDAI): 1.90±1.11 in 1stP vs 1.88±1.12 in 2nd P, p=0.907]. In the 2nd P the drug administration interval was higher for all three TNF inhibitors (Ifx: 8.52 ±1.43 weeks 1st P vs 9.7±1.44 weeks 2nd P p<0,001; Ada: 2.19 ± 0,58 weeks 1stP vs 2.95±1.58 weeks 2ndP p=0,007; Etn: 1.09±0,27 weeks 1stP vs 1.61 ±0,91 weeks 2ndP p=0.004). The weekly mean dose received per patient from each anti-TNF in the 2nd P was significantly lower than in the 1st P [Ifx (mg/kg/week): 0.51±0.14 at 1stP vs 0.42±0.12 at 2ndP, p<0.001; Ada (mg/week): 19.19±3.72 at 1stP vs 15.52±4.81 at 2ndP, p<0,001; Etn (mg/week) 42.09±13.25 at 1stP vs 35.04±13.37 at 2ndP, p=0.009]. The monthly amount of spared drug, converted in economic savings was 91.62 € per patient for Ifx (70kg of mean weight), 324 € per patient for Ada, 257 € per patient for Etn. The yearly amount of money saved in this group of 88 patients was 233.186 €.
Conclusions The therapeutic dose monitoring based on serum trough drug levels, used in rheumatic patients, has shown to be a useful tool to support therapeutic clinical practice in addition to enabling cost effective savings of biopharmaceuticals
De Vries, Ann Rheum Dis 2009;
Bartelds, Ann Rheum Dis 2007,
Pascual-Salcedo, Rheumatology 2011.
Acknowledgements Unrestricted Educational Grant by Pfizer
Disclosure of Interest None Declared