Elsevier

Vaccine

Volume 28, Issue 31, 12 July 2010, Pages 5109-5113
Vaccine

The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis

https://doi.org/10.1016/j.vaccine.2010.03.080Get rights and content

Abstract

Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Thirty-one children (mean age:12.9 ± 4.6 years) treated with anti-TNFs plus Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 32 age-matched children treated only with DMARDs were vaccinated with two doses of PCV7. After the first vaccine dose geometric mean titers (GMTs) were significantly increased for all vaccine serotypes (p < 0.0001) in both groups and were found to be protective (>0.35 μg/ml) in 87–100% of all children, depending on the serotype. Children receiving anti-TNFs achieved a significantly lower GMTs against serotypes 4, 14 and 23F (p < 0.05). A ≥4-fold increase of the baseline titers to ≥5 vaccine serotypes was observed in 50% and 75% of the anti-TNF and control patients, respectively (p = 0.0697). No patient developed vaccine-associated serious adverse events or disease flares.

Introduction

The production and application of anti-TNF agents has offered new perspectives in the treatment of patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA) [1], [2]. However, patients receiving these factors have increased susceptibility to infections, including pneumococcal respiratory tract infections [2], [3], [4]. Additionally, there is evidence that pneumococcal infections are associated with higher mortality rates during treatment with anti-TNF agents [4], [5]. These clinical data are supported by experimental studies. TNF-α has been shown to be increased in the serum and lung of mice infected with Streptococcus pneumoniae. Administration of anti-TNF in those mice resulted in a significant increase of the microbial load and mortality rate suggesting that TNF-α may play an important role in prevention and development of pneumococcal infection [6].

Based on these data, it has recently been proposed that patients with RA under anti-TNF or other immunosuppressive treatment should be vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) [7], [8]. After adopting this policy, a small number of studies on adults with chronic rheumatic diseases (CRD) have demonstrated controversial results regarding the effect of anti-TNF agents on the immunogenicity of PPV23 [9], [10], [11], [12], [13]. No relevant data have been published so far, for the 7-valent pneumococcal conjugate vaccine (PCV7) either in adults with RA or in children with JIA.

PCV7, a relatively new vaccine, offers new opportunities for protection in subjects at risk for invasive disease. Although, it has a relatively narrow spectrum of protection compared to the PPV23, it has been shown to be more effective due to its improved immunogenicity, duration of protection and the induction of immune memory [14]. Its administration in other groups of immunocompromised children (children with asplenia, HIV infection, solid organ or haematopoietic stem cell transplantation, and chronic renal disease) has shown that this vaccine is safe and immunogenic [15], [16], [17], [18], [19], [20], [21], [22].

In order to protect children with JIA who were followed up by our Center against severe pneumococcal infections we scheduled to vaccinate them with PCV7 and at the same time to investigate the effect of anti-TNF treatment on the safety and immunogenicity of this vaccine.

Section snippets

Inclusion criteria

Children with JIA who were followed up by our Pediatric Rheumatology Referral Center and treated with Disease Modifying Anti-Rheumatic Drugs (DMARDs, mainly methotrexate or cyclosporine) and anti-TNF agents with or without prednisone for at least 6 months were enrolled in the study.

Exclusion criteria

Children previously vaccinated against S. pneumoniae were excluded from the study.

Study population

Sixty-three children with different types of JIA were studied. Children were assigned into two groups (the study and the control

Results

The characteristics of the study and control groups of patients are shown in Table 1. No significant differences in gender, age, type of the disease, kind of DMARDs received and percentage of patients receiving prednisone were found between the two groups, except for the disease duration which was significantly longer in the study group (8.58 ± 4.25 vs 5.12 ± 3.24, p = 0.0024).

Discussion

To our knowledge, this is the first study to evaluate the immunogenicity and safety of PCV7 in children with JIA receiving immunosuppressive treatment including or not anti-TNF agents. It was found that after a single dose of PCV7, GMTs were significantly increased and above the cut-off level of 0.35 mg/ml for all 7 VS, regardless of anti-TNF treatment, the disease type and duration and baseline titers. GMTs to all VS were found to be lower – although above the cut-off level of 0.35 mg/ml – in

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