Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis
- Geertje M Bartelds1,
- Carla A Wijbrandts2,
- Michael T Nurmohamed3,
- Steven Stapel4,
- Willem F Lems3,
- Lucien Aarden4,
- Ben A C Dijkmans1,3,
- Paul Peter Tak2,
- Gerrit Jan Wolbink1,4
- 1Jan van Breemen Institute, Amsterdam, the Netherlands
- 2Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands
- 3VU Medical Center, Amsterdam, the Netherlands
- 4Sanquin Research, Amsterdam, the Netherlands
- Correspondence to:
MrG J Wolbink
Department of Rheumatology, Jan van Breemen Institute, Dr Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands;
- Accepted 4 February 2007
- Published Online First 14 February 2007
Background: A substantial proportion of patients with rheumatoid arthritis (RA) do not respond, or lose initial response, to adalimumab treatment. One explanation for non-response is that patients develop anti-adalimumab antibodies.
Objectives: To evaluate the incidence of formation of antibody against adalimumab and the association with serum adalimumab concentrations and clinical response.
Methods: In a cohort of 121 consecutive patients with RA treated with adalimumab, serum adalimumab concentrations and antibodies against adalimumab were measured together with clinical response variables before and up to 28 weeks after the start of treatment.
Results: Anti-adalimumab antibodies were detected in 21 patients (17%) during 28 weeks of treatment. EULAR non-responders had antibodies significantly more often than good responders (34% vs 5%; p = 0.032). Patients with antibodies showed less improvement in disease activity (mean (SD) delta DAS28 0.65 (1.35)) than patients without antibodies (mean delta DAS28 1.70 (1.35)) (p = 0.001). Patients with antibodies during follow-up had lower serum adalimumab concentrations at 28 weeks than patients without antibodies (median 1.2 mg/l, range 0.0–5.6 vs median 11.0 mg/l, range 2.0–33.0, respectively; p<0.001). Good responders had higher serum adalimumab concentrations than moderate responders (p = 0.021) and non-responders (p = 0.001). Concomitant methotrexate use was lower in the group with anti-adalimumab antibodies (52%) than in the group without antibodies (84%) (p = 0.003).
Conclusions: Serum antibodies against adalimumab are associated with lower serum adalimumab concentrations and non-response to adalimumab treatment.
- DAS28, disease activity score in 28 joints
- DMARD, disease-modifying anti-rheumatic drug
- EULAR, European League Against Rheumatism
- HACA, human anti-chimeric antibody
- RA, rheumatoid arthritis
- TNF, tumour necrosis factor
Published Online First 14 February 2007
Funding: Abbott Laboratories. CAW is supported by a grant (945-02-029) from the Netherlands Organization for Health Research and Development (ZonMw). The study sponsors had no involvement in the study design, the collection, analysis, and interpretation of data, the writing of the report, or the decision to submit the paper for publication.
Competing interests: Professor Dijkmans and Professor Tak are members of the advisory board of Abbott and have received honoraria for lectures.