Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis

Abstract

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 antiadalimumab 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 antiadalimumab 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.

Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double‐blind, placebo‐controlled, dose‐ranging study

“…The detection of antibodies is dependent on the patient population studied, the timing and frequency of serum sampling, and the sensitivity and specificity of the detection assay used. Thus, the reported incidence can vary greatly between studies of the same biologic agent (3,15,16). In the present study, we employed a sensitive assay to study antibody production both while patients were receiving study medication, as is typically reported for other products, and after a 20-week washout following the last study injection, when golimumab concentrations would likely be low enough to minimize interference with antibody detection.…”

Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis

“…The expressions of antibodies to TCZ may reduce efficacy and systemic reactions to injections of anti‐TNF inhibitors would occasionally cause lack of efficacy due to the expression of antidrug antibodies 16, 17, 18, 19. In a previous study, we found the anti‐TCZ antibody frequency to be increased in TCZ‐SC patients as compared to TCZ‐IV patients in the double‐blind setting 9.…”

Anti‐adalimumab antibodies in rheumatoid arthritis patients are associated with interleukin‐10 gene polymorphisms

“…Inadequate response to tumor necrosis factor ␣ (TNF␣)-blocking therapy in rheumatoid arthritis (RA) may result from the formation of antibodies against these drugs (1). Previous studies have shown that polymorphisms in the promoter region of the gene for interleukin-10 (IL-10), a cytokine with a key role in antibody formation, are associated with the formation of antibodies that inhibit recombinant factor VIII (FVIII) in hemophilia (2) and with the development of autoantibodies against nicotinic acetylcholine receptor (nAChR) in myasthenia gravis (MG) (3).…”