Article

Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis

Immunology Unit, Hospital La Paz, Paseo de La Castellana 261, 28046 Madrid, Spain.
Rheumatology (Oxford, England) (Impact Factor: 4.48). 03/2011; 50(8):1445-52. DOI: 10.1093/rheumatology/ker124
Source: PubMed

ABSTRACT

To analyse the clinical relevance of the production of anti-infliximab antibodies (anti-infliximab Abs) in patients with RA undergoing infliximab treatment over a prolonged period of time.
Clinical characteristics, serum trough infliximab and antibody levels were evaluated in 85 RA patients treated with infliximab for a median of 4.42 (interval 0.4-10.2) years. DAS in 28 joints (DAS-28), EULAR response criteria and survival of treatment were assessed at 3 time points (6 months, 12 months and >4 years).
Antibodies against infliximab were detected in 28 (32.9%) patients and were present in all EULAR non-responder patients. Antibody levels were higher in EULAR non-responders throughout the study period (P = 0.05 at 6 months, P = 0.02 at 1 year, P = 0.003 at >4 years) compared with EULAR (good and moderate) responders. Nine (10.5%) patients, all of them with high-serum anti-infliximab Ab levels, developed infusion-related reactions. Patients with anti-infliximab Abs more often required increased infliximab doses (51.7%) (P = 0.032) and median survival time on treatment was shorter (4.15 vs 8.89 years) (P = 0.0006). MTX co-therapy was not associated with lower proportion of anti-infliximab Ab-positive patients, but those receiving both infliximab and MTX had lower levels of anti-infliximab Abs (P = 0.073) and longer survival (P = 0.015) on treatment.
The formation of anti-infliximab Abs during treatment with infliximab is associated with a loss of clinical response, the appearance of infusion reactions and discontinuation of treatment.

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Available from: Antonio Martínez, Jan 20, 2014
    • "Factor VIII products were also withdrawn due to increased development of NAb in hemophilia A patients [34] [35] [36]. Other examples of ADA-associated adverse effects include infusion reactions in Crohn's disease and RA patients receiving anti-TNF treatments [10] [11], severe anaphylaxis with recombinant interferon beta [37], and anaphylaxis after treatment with Factor IX [38]. Various types of ADA have been observed during TPP treatment, mostly IgG, but also IgE, IgM and IgA. "
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    • "It identifies those patients who will benefit from dose escalation versus those who are unlikely to respond to this strategy (high titers of anti-drug antibodies) [33]. Drug immunogenicity is one of the main mechanisms behind therapeutic failure also for RA patients [34] [35] [36] [37] [38]. "
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    • "The immunogenicity of biological therapies has been shown to influence secondary inefficacy in rheumatic diseases [17,28,42-52]. The frequency of ADA development in SpA patients varies between different studies (25.5 to 29% for antibodies to Ifx and 31% for antibodies to Ada) [17,19,20,49-51]. "
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