Background/Purpose: Biological therapy has proved efficacious in various chronic inflammatory arthropathies but, in practice, clinical efficacy is reduced in some patients, suggesting drug-induced immunogenicity as a possible mechanism. Our objective was to analyze the development of tumor necrosis factor (TNF) antagonist antibodies (AB) and serum drug levels in patients with loss of treatment or adverse events in clinical practice.

Methods: Descriptive, retrospective study of patients attended by a tertiary hospital rheumatology department between February 2012 and May 2013, who were on active  TNF antagonist treatment and suffered loss of efficacy or adverse treatment effects. Patients were included according to clinical judgment. We measured antidrug AB and serum drug levels using an ELISA immunoassay (Promonitor®). Only patients on infliximab (IFX), etanercept (ETN) or adalimumab (ADA) were analyzed. All blood samples were obtained in the 24 h before the next scheduled dose of treatment. Only patients with positive AB were finally analyzed. The following variables were collected: demographic variables; diagnosis and disease duration; previous and current treatment; reason for the analysis; antidrug AB and serum drug levels; and, the clinical decision.

Results: Seventy patients were included; 67% female; mean age 51±14 years. The main diagnoses were: rheumatoid arthritis (RA) (54.3%); ankylosing spondylitis (AS) (20%); psoriatic arthritis (PsA) (10%); and miscellaneous (MISC) (15.7%), which included, among others, Behçet disease, undifferentiated spondyloarthropathy and juvenile idiopathic arthritis. The reason for the analysis was: loss of efficacy in 47% of patients, adverse events in 47%, and partial response in 6%. Seventeen patients (24.3%) developed antidrug AB:11 anti-ADA and 6 anti-IFX, representing 36.6% and 40%, respectively, of study patients on these treatments. Antidrug AB were found directly in 14/17 patients and by a dissociation method in the remaining 3 patients. In 15 patients, serum drug levels were undetectable and in 2 cases (1 ADA and 1 IFX), both analyzed by the dissociation method, suboptimal (suboptimal level ADA: 0.04-0.80 ng/ml and IFX: 0.05-1.50 ng/ml). Diagnoses were: 8 RA; 4 AS; 2 PsA; and 3 MISC. Eight of 17 patients received concomitant synthetic DMARDs (4 leflunomide, 2 methotrexate, 1 sulphasalazine and 1 mycophenolate). The remaining 9 received biological therapy in monotherapy. Nine out of 17 had previously received another biological agent (7 anti-TNF and 2 non anti-TNF), which was discontinued due to inefficacy or adverse events. After development of antidrug AB, 15 patients were withdrawn from current biological therapy: 12 were switched to another anti-TNF agent and 3 to a non anti-TNF drug with a good response. Of the remaining two patients, one was lost to follow up and the other is still receiving the same treatment with methotrexate added with a good response.

Conclusion: In this study, 24.3% of patients with loss of efficacy or adverse events to TNF antagonists developed antidrug AB, which were only observed in patients receiving monoclonal antibodies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunogenicity-induced-by-tumor-necrosis-factor-antagonists-in-chronic-inflammatory-arthropathies-retrospective-study-in-clinical-practice-conditions/