Background Increasing evidence suggests that therapeutic drug monitoring is useful in rheumatological patients receiving anti-TNF therapy. By measuring anti-drug antibodies (ADA) and serum drug levels the therapy may be optimized.
Objectives To investigate the serum infliximab concentrations and the occurrence of anti-infliximab antibodies in patients receiving infliximab in daily clinical practice.
Methods All arthritis patients receiving infliximab in three Finnish rheumatological departments were recruited for this cross-sectional study. Anti-drug antibodies and trough serum drug levels were measured before next infliximab infusion. Demographic data of the patients were collected and disease activity was measured. If needed, the treatment of patients was changed on the basis of serum drug level and ADA measurements according to the judgement of the rheumatologist.
Results The patient population consisted of 126 patients (31 rheumatoid arthritis (RA), 62 spondylarthritis (SpA), 27 juvenile arthritis (JIA) and 6 seronegative oligoarthritis patients). The median (IQR) duration of infliximab treatment was 35 (12-73) months, and the mean (±SD) dose 294 (±91) mg and interval 8 (±1) weeks. 83 patients (66%) were receiving methotrexate (mean dose 18±6 mg). 13 out of 126 patients (10%) had ADA against infliximab. In 9 out of 13 patients, infliximab serum levels were undetectable and in the remaining 4 patients they were low (0.02 - 0.3 mg/ml). The occurrence of ADA was associated with the diagnosis: 6 patients with RA (19%), 1 patient with SpA (2%), 3 patients with JIA (11%) and 3 patients with seronegative oligoarthritis (50%) had ADA against infliximab (p<0.001). ADA-positive patients were receiving lower weekly dose of infliximab (31±10 mg/wk; mean ± SD) compared to ADA-negative patients (40±17 mg/wk; p 0.025). The number of patients receiving methotrexate or the dose of methotrexate were not significantly different between ADA-positive and -negative patients. Infliximab was terminated in all 13 ADA-positive patients. In 7 of 13 patients, disease activity was low, and no other biologic therapy was started. Regarding infliximab serum concentrations, 65 of 126 patients (52%) had optimal infliximab levels (2-10 mg/ml). In 38 patients (30%), infliximab levels were low (0.02 – 1.9 mg/ml) and in 13 patients (10%) they were high (>10 mg/ml).
Conclusions In this clinical cohort, ADA against infliximab were observed at lower frequency than generally described in clinical studies. The occurrence of ADA was lowest in SpA patients. Significant proportion of the immunized patients had inactive disease, and their treatment was continued without biologic therapy, leading to savings in treatment costs. Furthermore, only every other patient had optimal infliximab serum levels, supporting the use of therapeutic drug monitoring in patients receiving infliximab.
Disclosure of Interest None declared