Background An important factor influencing pharmacokinetics of adalimumab is immunogenicity. There is a dose-dependent effect of methotrexate (MTX) on the amount of anti-drug antibodies produced against adalimumab . Consequently, patients concomitantly treated with MTX have higher adalimumab trough levels than patients without concomitant MTX, resulting in a more beneficial clinical response . Whether other disease modifying anti-rheumatic drugs (DMARDs) have a comparable effect on adalimumab levels has not yet been investigated.
Objectives To investigate the effect of co-treatment with different DMARDs on adalimumab trough levels in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA).
Methods In this observational cohort study at the Jan van Breemen Research Institute | Reade, Amsterdam a total of 375 consecutive patients (272 RA patients and 103 PsA patients) treated with adalimumab were included. Adalimumab trough concentrations were measured at 0, 4, 16 and 28 weeks of treatment, using an enzyme-linked immunosorbent assay (ELISA). Data was analysed using the General Estimating Equation. Last observation carried forward was used for patients stopping adalimumab therapy prematurely. In addition, in 29 patients the last available drug level before adalimumab dose was increased to 40 mg sc every week was carried forward.
Results Four groups of adalimumab treated patients were compared: monotherapy (n=67); concomitant MTX (n=224); concomitant other DMARDs (leflunomide, hydroxychloroquine, sulphasalazine or a combination of these) (n=26) and MTX + other DMARDs (n=58). Adalimumab trough levels are shown in figure 1. These levels were significantly higher in patients with concomitant DMARD treatment as compared to monotherapy: monotherapy vs. other DMARDs p=0.011; monotherapy vs. MTX p<0.001; and monotherapy vs. MTX + other DMARDs p<0.001. There was no statistical difference between both MTX groups and the other DMARDs group (p=0.579 [MTX vs. other DMARDs] and p=0.352 [MTX + other DMARDs vs. other DMARDs]).
Conclusions Adalimumab trough concentrations are the highest in patients concomitantly taking MTX, with or without other DMARDs. Patients on adalimumab monotherapy had the lowest levels. Other DMARDs than MTX also seem to have a beneficial effect on adalimumab trough concentrations, however, these results have to be interpreted carefully, since only 26 patients were included in the “other DMARDs” group.
Krieckaert et al. ARD 2012.
Pouw et al. ARD 2013 online first.
Disclosure of Interest C. Krieckaert Speakers bureau: Pfizer, Abbvie, E. Vogelzang: None declared, M. Pouw: None declared, M. Nurmohamed Grant/research support: Abbvie, BMS, MSD, Pfizer, UCB and Roche, Consultant for: Abbott, BMS, Pfizer and Roche, Speakers bureau: AbbVie, Pfizer and Roche., G. Wolbink Grant/research support: Pfizer, Speakers bureau: Pfizer, Amgen
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