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Immunogenicity of Anti-TNF-α Agents in Autoimmune Diseases

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Abstract

Prognosis of several autoimmune diseases, especially rheumatoid arthritis (RA), ankylosing spondylitis, Crohn’s disease (CD), and psoriasis, usually refractory to conventional treatment improved considerably with the introduction of tumor necrosis factor alpha (TNF-α) antagonistic agents, which is now available (infliximab, etanercept, and adalimumab). However, a portion of patients persists with active disease, infusion reactions, and relapses even during current biological therapy. One of the reasons for this is the associated immunogenicity to these drugs. The incentive for induction of antibodies against anti-TNF-α agent depends mainly on its constitution. Chimerical drugs have a higher capacity of inducing immunogenicity compared to completely human drugs. Among the three anti-TNF-α agents, this phenomenon has been studied mainly in patients using infliximab, especially in RA and CD. The prevalence of anti-infliximab antibodies in RA varies from 12% to 44% and seems to be inversely proportional to the level of seric infliximab and therapeutic response. The use of etanercept was associated to the development of anti-etanercept antibodies in 0% to 18% of patients, without apparent effect on effectiveness or adverse events. Studies with RA and CD patients show prevalence of anti-adalimumab antibodies from 1% to 87%. Immunosuppressive drug addiction can reduce the induction of anti-TNF-α antibodies.

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Acknowledgments

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; grant 06/61303-7 to CDMAC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ; grants 305468/2006-5 to EB and 300248/2008-3 to CAAS), and Federico Foundation Grant to EB and JFC.

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Authors and Affiliations

  1. Pediatric Rheumatology Unit of Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo University, São Paulo, Brazil

    Nádia Emi Aikawa & Clovis Artur Almeida Silva

  2. Rheumatology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo University, São Paulo, Brazil

    Jozélio Freire de Carvalho & Eloísa Bonfá

  3. Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, no. 455, 3° andar, sala 3190-Cerqueira César, São Paulo, São Paulo, CEP 05403-010, Brazil

    Jozélio Freire de Carvalho

  4. Centro de Dispensação de Medicação de Alto Custo (CEDMAC), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Nádia Emi Aikawa, Jozélio Freire de Carvalho, Clovis Artur Almeida Silva & Eloísa Bonfá

Authors
  1. Nádia Emi Aikawa
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  2. Jozélio Freire de Carvalho
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  3. Clovis Artur Almeida Silva
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  4. Eloísa Bonfá
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Corresponding author

Correspondence to Jozélio Freire de Carvalho.

Additional information

Take-home messages

• Anti-human anti-chimeric (anti-HACA) antibodies were described in the majority of diseases treated with anti-TNF.

• In some cases, anti-HACA may be associated with poor treatment’s response to anti-TNF therapy and high frequency of infusion reactions.

• Concomitant use of immunosuppressive drug may reduce anti-HACA production.

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Emi Aikawa, N., de Carvalho, J.F., Artur Almeida Silva, C. et al. Immunogenicity of Anti-TNF-α Agents in Autoimmune Diseases. Clinic Rev Allerg Immunol 38, 82–89 (2010). https://doi.org/10.1007/s12016-009-8140-3

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  • DOI: https://doi.org/10.1007/s12016-009-8140-3

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