Immune response to influenza A/H1N1 vaccine in inflammatory bowel disease patients treated with anti TNF-α agents: effects of combined therapy with immunosuppressants

J Crohns Colitis. 2013 May;7(4):301-7. doi: 10.1016/j.crohns.2012.05.011. Epub 2012 Jun 5.

Abstract

Background and aims: Our first objective was to evaluate the immune response to the adjuvanted 2009 A/H1N1 pandemic (pH1N1) vaccine in inflammatory bowel disease (IBD) patients treated with anti-TNF-α alone or combined with immunosuppressants (IS). Second and third aims were the safety of pH1N1 vaccine and the effects on IBD clinical activity.

Methods: 36 patients with Crohn's disease (CD) and 26 with ulcerative colitis (UC) and thirty-one healthy control (HC) subjects were enrolled. 47 patients were on anti TNF-α maintenance monotherapy and 15 on anti TNF-α combined with IS. Sera were collected at baseline (T0) and 4 weeks after the vaccination (T1) for antibody determination by hemagglutination inhibition (HAI). Disease activity was monitored at T0 and T1.

Results: Seroprotective titers (≥1:40) in patients were comparable to HC. Seroconvertion rate (≥4 fold increase in HAI titer) was lower than HC in IBD patients (p=0.009), either on anti TNF-α monotherapy (p=0.034) or combined with IS (p=0.011). Geometric mean titer (GMT) of antibodies at T1 was significantly lower in patients on combined therapy versus those on monotherapy (p=0.0017) and versus HC (p=0.011). The factor increase of GMT at T1 versus T0 was significantly lower in IBD patients versus HC (p=0.042), and in those on combined immunosuppression, both versus monotherapy (p=0.0048) and HC (p=0.0015). None of the patients experienced a disease flare.

Conclusion: Our study has shown a suboptimal response to pH1N1 vaccine in IBD patients on therapy with anti TNF-α and IS compared to those on anti-TNF-α monotherapy and HC.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adalimumab
  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Viral / blood
  • Biomarkers / blood
  • Case-Control Studies
  • Certolizumab Pegol
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / immunology*
  • Crohn Disease / drug therapy
  • Crohn Disease / immunology*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects
  • Immunoglobulin Fab Fragments / therapeutic use
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Infliximab
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Prospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Biomarkers
  • Immunoglobulin Fab Fragments
  • Immunosuppressive Agents
  • Influenza Vaccines
  • Polyethylene Glycols
  • Infliximab
  • Adalimumab
  • Certolizumab Pegol