Journal Article

POS0681 ARE JAKi PLASMA LEVELS RELATED TO CLINICAL RESPONSE IN RHEUMATOID ARTHRITIS?: THE MEASURE STUDY, A MULTICENTRE PROSPECTIVE COHORT STUDY

Gómez-Centeno, A., Frade-Sosa, B., Borrell Paños, H., Mateo, L., Valero, C., Chacur, C. A., Tobalina, L., Inciarte-Mundo, J., Zubiaur, P., Novella-Navarro, M., Marsal Barril, S., Prior-Español, Á., Villapalos, G., Sanmarti, R., Graell, E., Balsa, A., Sapena, N., Garcia-Vicuña, R.

2024

Overview

Background:Baricitinib (BARI) and tofacitinib (TOFA) are Janus kinase inhibitors (JAKi) approved for treating rheumatoid arthritis (RA). Phase II clinical trials have shown a significant dose-response relationship for JAKi. However, there’s a lack of studies analyzing the correlation between blood drug levels and clinical response in RA [1].Objectives:To evaluate the precision of drug plasma levels in discerning the clinical disease status of RA patients receiving BARI and TOFA.Methods:Multicenter, non-interventional prospective study involving RA patients receiving BARI or TOFA, according to clinical judgment. Patients were enrolled during their first follow-up visit after initiating JAKi treatment (at 12-16 weeks). The primary endpoints was to determine the accuracy of drug plasma levels in discerning clinical disease status based on the Clinical Disease Activity Index (CDAI). BARI and TOFA levels were determined simultaneously by liquid chromatography tandem mass spectrometry (LC-MS/MS)[2]. C max (after 45min of drug administration) and C min (just before drug intake) was analysed in each patient.Results:Fourty-nine patients (84% female, 86% seropositive (RF and/or ACPA), mean age 54 ± 12.9 years and mean RA duration 10±8.4 years) were included: 44 received BARI and 5 TOFA. The mean number of previously administered biological DMARDs was 1.1±1.5. Three patients had received previous treatment with another JAKi. The mean DAS28 and CDAI at JAKi initiation were 4.63±1.25 and 21.6±9.0, respectively. At the 12–16-week visit, 37 patients (75.5%) achieved remission or low disease activity according to CDAI, with a mean DAS28 and CDAI of 2.62±1.25 and 8.0±7.2, respectively (Table 1). Table 2 summarizes the mean drug plasma levels according to CDAI score. Drug plasma levels (both Cmax and Cmin) showed similar results in patients with different disease activity statuts according to CDAI, without significant differences. However, the two patients treated with BARI and high disease activity showed the lower drug levels, although the difference was not significant.Conclusion:In this preliminary study, no clear dose-response relationship was found between plasma JAKi levels and disease activity in RA. However further studies including patients with moderate/high disease activity are needed to assess the potential usefulness of evaluating plasma drug levels as indicator of the clinical status of RA patients undergoing treatment with BARI and TOFA.REFERENCES:[1] Kremer JM, Cohen S, Wilkinson BE, Connell CA, French JL, Gomez-Reino J, et al. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum 2012;64:970-81.[2] Koller D, Vaitsekhovich V, Mba C, Steegmann JL, Zubiaur P, Abad-Santos F, et al. Effective quantification of 11 tyrosine kinase inhibitors and caffeine in human plasma by validated LC-MS/MS method with potent phospholipids clean-up procedure. Application to therapeutic drug monitoring. Talanta 2020;208:120450.Acknowledgements:NIL.Disclosure of Interests:Beatriz Frade-Sosa received support for attending meetings and/or speaker honoraria from Pfizer, AbbVie, Lilly, BMS, Galápagos, Sandoz and GSK., Chafik Alejandro Chacur: None declared, Jose Inciarte-Mundo Current employee at Astrazeneca., Cristina Valero: None declared, Marta Novella-Navarro: None declared, Helena Borrell Paños: None declared, Águeda Prior-Español: None declared, Eduard Graell: None declared, Pablo Zubiaur: None declared, Gonzalo Villapalos: None declared, Nuria Sapena: None declared, Lola Tobalina: None declared, Antonio Gómez-Centeno: None declared, Lourdes Mateo: None declared, Alejandro Balsa: None declared, Sara Marsal Barril: None declared, Rosario Garcia-Vicuña: None declared, Raimon Sanmarti: None declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Blood levels / Caffeine / Clinical trials / Disease-modifying Drugs (DMARDs) / Dose-response relationship / Drug dosages / Enzyme inhibitors / Janus kinase / Liquid chromatography / Mass spectroscopy / Methotrexate / Non-pharmacological intervention / Patients / Phospholipids / Plasma / Plasma levels / Remission / Rheumatoid arthritis / Scientific Abstracts / Targeted synthetic drugs