No correlations between the development of specific IgA and IgM antibodies against anti-TNF blocking agents, disease activity and adverse side reactions in patients with rheumatoid arthritis

Maurizio Benucci, Gianantonio Saviola, Francesca Meacci, Mariangela Manfredi, Maria Infantino, Paolo Campi, Maurizio Severino, Miriam Iorno, Piercarlo Sarzi-Puttini, Fabiola Atzeni

Research output: Contribution to journalArticle

Abstract

The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases, including rheumatoid arthritis (RA). However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological agents, disease activity and the development of class-specific IgA and IgM antibodies against the three anti-TNF agents in patients with RA. This longitudinal observational study involved consecutive outpatients with active RA who started treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF-α agents were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean age of the 99 patients (86% females) was 54.6±12.4 years, and the median disease duration was 11.2±.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anticitrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28- joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that the development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity.

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalOpen Rheumatology Journal
Volume7
Issue number1
DOIs
Publication statusPublished - 2013

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Immunoglobulin A
Immunoglobulin M
Anti-Idiotypic Antibodies
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Antibodies
Immune Complex Diseases
Therapeutics
Immediate Hypersensitivity
Joint Diseases
Rheumatoid Factor
Blood Sedimentation
Biological Factors
Proxy
Etanercept
Adalimumab
Allergy and Immunology
Rheumatic Diseases
Serum
Pharmaceutical Preparations

Keywords

  • Adverse events
  • Antibodies
  • Disease activity
  • Rheumatoid arthritis
  • TNF blockers

ASJC Scopus subject areas

  • Rheumatology

Cite this

No correlations between the development of specific IgA and IgM antibodies against anti-TNF blocking agents, disease activity and adverse side reactions in patients with rheumatoid arthritis. / Benucci, Maurizio; Saviola, Gianantonio; Meacci, Francesca; Manfredi, Mariangela; Infantino, Maria; Campi, Paolo; Severino, Maurizio; Iorno, Miriam; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola.

In: Open Rheumatology Journal, Vol. 7, No. 1, 2013, p. 75-80.

Research output: Contribution to journalArticle

Benucci, Maurizio ; Saviola, Gianantonio ; Meacci, Francesca ; Manfredi, Mariangela ; Infantino, Maria ; Campi, Paolo ; Severino, Maurizio ; Iorno, Miriam ; Sarzi-Puttini, Piercarlo ; Atzeni, Fabiola. / No correlations between the development of specific IgA and IgM antibodies against anti-TNF blocking agents, disease activity and adverse side reactions in patients with rheumatoid arthritis. In: Open Rheumatology Journal. 2013 ; Vol. 7, No. 1. pp. 75-80.
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AU - Benucci, Maurizio

AU - Saviola, Gianantonio

AU - Meacci, Francesca

AU - Manfredi, Mariangela

AU - Infantino, Maria

AU - Campi, Paolo

AU - Severino, Maurizio

AU - Iorno, Miriam

AU - Sarzi-Puttini, Piercarlo

AU - Atzeni, Fabiola

PY - 2013

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N2 - The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases, including rheumatoid arthritis (RA). However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological agents, disease activity and the development of class-specific IgA and IgM antibodies against the three anti-TNF agents in patients with RA. This longitudinal observational study involved consecutive outpatients with active RA who started treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF-α agents were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean age of the 99 patients (86% females) was 54.6±12.4 years, and the median disease duration was 11.2±.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anticitrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28- joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that the development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity.

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KW - TNF blockers

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