Objectives To determine serum trough levels and anti-drug antibodies (Ab) in patients with rheumatoid arthritis (RA) or polyarticular psoriatic arthritis (PsA) in clinical remission (CR) or low disease activity (LDA) on treatment with adalimumab (ADA), etanercept (ETN) and infliximab (IFX) and correlate serum trough levels and Ab with loss of CR o LDA after 1-year of follow-up.
Methods Prospective, multicenter study of patients diagnosed with RA or PsA attended by 3 hospital outpatient clinics in Catalonia,Spain treated with ADA, ETN or IFX for ≥3 months in CR or with LDA measured by DAS28-ESR at ≥2 consecutive visits. We determined Ab and serum trough levels (commercial ELISA Kit Promonitor®, Progenika SA) at 0,4,8 and 12 months. Variables collected: demographic data; disease activity (different articular indexes), diagnosis; disease duration; biologic drug; reduced dose, and concomitant DMARDs therapy. Study entry data (Visit 0) are presented.
Results 165 patients (RA 92 [55.8%], PsA 73 [44.2%]),65.5% female, mean age 57±12 years were included. 121 (73.3%) patients were in CR, 44 (26.7%) with LDA, 63 on ADA, 83 ETN, and 19 IFX. Mean treatment duration was 65.2±40.7 months. 75 patients (45%) were receiving low doses of biologics, and 98 (59.4%) concomitant DMARD (84% methotrexate). In 3 patients (1.8%, 2 in CR and receiving DMARD) significant Ab levels were found, with undetectable serum trough levels (2RA and 1PsA): 2 anti-IFX (10%) and 1 anti-ADA (1.6%). Another patient receiving ADA had low Ab titers and detectable serum drug levels. Mean serum levels of all TNF antagonists were non-significantly different between RA and PsA, monotherapy or combined treatment. Patients with reduced dosage had significantly-lower levels of ADA and ETN than those receiving standard doses. No differences between patients in CR or LDA were observed. According to the ELISA cut-off for appropriate drug serum levels (ADA: >1.274μg/ml, and ETN :>1.242μg/ml) (Chen DY et al. Ann Rheum Dis 2014;0:1-9), 19% and 30.1% of patients treated with ADA and ETA, respectively, had suboptimal levels (30% with ADA and 46.2% with ETA on dose reduction). There were no differences between DAS28-CPR, DAS28-ESR, SDAI, CDAI, ESR or CRP values in patients with suboptimal or appropriate serum levels.
Conclusions The frequency of anti-drug antibodies is very low in patients with RA and PsA treated with TNF antagonists in CR or with LDA. A significant percentage of patients had suboptimal drug serum trough levels. Prospective follow-up will determine whether these serum levels may predict loss of CR or LDA.
Disclosure of Interest R. Sanmarti Grant/research support: Unrestricted grant from Pfizer, J. Inciarte Grant/research support: Grant from Hospital Clinic of Barcelona (Premi Emili Letang 2013), P. Estrada Alarcόn: None declared, M. Garcia Manrique: None declared, A. Gonzalez Navarro: None declared, J. Narvaez Grant/research support: Unrestricted grant from Pfizer, J. Rodríguez-Moreno Grant/research support: Unrestricted grant from Pfizer, A. Gomez-Centeno Grant/research support: Unrestricted grant from Pfizer, J. Yagüe Grant/research support: Unrestricted grant from Pfizer