Monitoring drug and antidrug levels: a rational approach in rheumatoid arthritis patients treated with biologic agents who experience inadequate response while being on a stable biologic treatment.

Diana Mazilu,Giorgiana Luca,Alexandra Peltea,Violeta Bojinca,Ioana Saulescu,Daniela Opriş,Cecilia Gainaru,Ruxandra Ionescu,Cosmin Constantinescu,Denisa Predeteanu,Andra Balanescu,Mihaela Iliuta,Natalia Apetrei,Andreea Borangiu,Tania Gudu,Laura Groseanu

doi:10.1155/2014/702701

Abstract

Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P = 0.038) with lower DAS28 and SDAI scores (P = 0.01 and P = 0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P = 0.002 and P = 0.023), DAS28 score (P = 0.002 and P = 0.003), and SDAI score (P = 0.001 and P = 0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can result in substantial morbidity [1,2,3], impaired physical activity, and poor quality of life [4, 5], leading to a reduced life expectancy by 3 to 18 years [6] and increased mortality [7,8,9,10,11].The targets of biologic agents are interactions between the immune cells, which are responsible for inflammation and structural damage in affected joints, and the signaling molecules involved in their activation
The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in rheumatoid arthritis (RA) patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment
Since there is no definition validated, we considered the situation as RA flare when at least one of the following conditions occurred: an increase in Simplified Disease Activity Index (SDAI), an increase in ESR and/or CRP not due to a concomitant infection, an increase in DAS score to moderate or high disease activity, and a lower class in European League Against Rheumatism (EULAR) response as compared to previous reevaluation

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can result in substantial morbidity [1,2,3], impaired physical activity, and poor quality of life [4, 5], leading to a reduced life expectancy by 3 to 18 years [6] and increased mortality [7,8,9,10,11].The targets of biologic agents are interactions between the immune cells (mainly T lymphocytes, B lymphocytes, and macrophages), which are responsible for inflammation and structural damage in affected joints, and the signaling molecules involved in their activation. The most used approved biologic agents for the treatment of RA are tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, etanercept, golimumab, and certolizumab) or products that target B cells like rituximab (a chimeric monoclonal antibody that targets CD20 B cells) or inhibitor of costimulation of T cells (abatacept). Since the introduction of biologic treatment, prognosis of the disease has been substantially improved [22, 23] Despite all these therapeutic advances and their relatively expensive costs, a variable proportion of patients with several autoimmune diseases including RA and inflammatory bowel diseases (IBD), who initially benefited from biologics, eventually lost response [24,25,26]. The rational for lack or loss of response is multifactorial: molecular structure of biologic drug, pharmacokinetics, pharmacodynamics, and development of anti-drug antibodies

Methods

Results

Conclusion