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While the majority of patients with psoriatic arthritis (PsA) respond well to treatment with adalimumab, some patients lose response.1 An explanation might be the development of antiadalimumab antibodies, which has been reported in rheumatoid arthritis.2 3 Therefore, we studied the incidence of antiadalimumab antibodies in PsA, and the relationship with serum adalimumab concentration and clinical response.
Twenty-two patients with active PsA, fulfilling CASPAR classification criteria,4 started adalimumab treatment (table 1). The patients met the requirements of the Dutch consensus on initiation of tumour necrosis factor blocking therapy in PsA5 and were seen at baseline, and after 3 and 12 months. Serum samples were collected just before the next injection with adalimumab. The Disease Activity Score in 28 joints (DAS28), which has been shown to discriminate between active drug and placebo in clinical trials in PsA, was chosen to monitor clinical disease activity, and EULAR response criteria were applied.6,–,8 All patients continued to receive adalimumab 40 mg every other week for 12 months.
Trough serum adalimumab concentrations were measured by ELISA, and anti-adalimumab antibodies were detected by radioimmunoassay.2 The antibody test was considered positive when antibody concentrations exceeded 12 AU/ml and adalimumab concentration was <5 mg/l.
Mean (SEM) DAS28 decreased from 4.9 (0.3) at baseline to 2.9 (0.3) after 3 months, and 2.9 (0.3) after 12 months (p<0.001 for both). At 3 months there were 12 moderate and 10 good responders. At 12 months there were four non-responders, eight moderate and 10 good responders.
In four patients (18%) anti-adalimumab antibodies were detected at any time point. After 3 months, three patients had low concentrations of anti-adalimumab antibodies (<100 AE/ ml), two of those developed high concentrations (>100 AE/ml) at 12 months. In the third patient the antibodies had disappeared at 12 months, but a fourth patient demonstrated a low concentration of antibodies at 12 months.
The median adalimumab concentration at 3 months was 7.8 mg/l (range 0.9–16.7), and 7.0 mg/l (undetectable–21.8) at 12 months. Patients with anti-adalimumab antibodies had lower median adalimumab concentrations than those without: 1.7 vs 8.1 mg/l (p=0.007) at 3 months, and 1.7 vs 9.8 mg/l (p=0.031) at 12 months. Adalimumab concentration was undetectable in patients with high concentrations of antibodies.
The reduction in adalimumab concentration may be caused by formation and increased clearance of adalimumab–anti-adalimumab immune complexes. This may explain the loss of response in some patients, but not all, as demonstrated by the fact that two of four non-responders at 12 months had anti-adalimumab antibodies and low adalimumab concentrations. One non-responder had a low adalimumab concentration (3.8 mg/l) without detectable antibodies, the fourth had normal adalimumab levels.
Patients with antibodies appeared to lose their initial good response (fig 1). Our study was not designed to examine whether concomitant methotrexate treatment could reduce the formation of anti-adalimumab antibodies.
In conclusion, anti-adalimumab antibodies develop in a minority of patients with PsA, and are associated with lower serum levels of adalimumab and diminished clinical response to treatment.
Competing interests BACD is a member of the advisory board of Abbott and has received honoraria for lectures. PPT has served as a consultant to Abbott, Schering-Plough, UCB and Wyeth.
Ethics approval Ethics committee approval from Academic Medical Centre/University of Amsterdam.
Patient consent Patient consent received.
Provenance and peer review Not commissioned; externally peer reviewed.
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