Rheumatoid arthritis
The Effect of Infliximab and Timing of Vaccination on the Humoral Response to Influenza Vaccination in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

https://doi.org/10.1016/j.semarthrit.2008.12.002Get rights and content

Objectives

To assess the effect of the timing of vaccination in relation to administration of infliximab on the efficacy and safety of influenza vaccine in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS).

Methods

The study population comprised 38 patients treated with infliximab at a mean dosage of 3 mg/kg (20 RA patients; 18 AS patients; 23 RA controls (treated with disease modifying antirheumatic drugs other than anti-tumor necrosis factor-α; and 17 healthy controls). Split-virion inactivated vaccine containing 15 μg hemagglutinin/dose of each of A/New Caledionan/20/1999 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (M) was used. Patients treated with infliximab were divided into 2 groups: 22 were vaccinated on the day of administration of infliximab, while 16 received the vaccine 3 weeks after infliximab. Baseline and 4- to 6-week clinical assessment of disease activity included erythrocyte sedimentation rate and C-reactive protein for all patients, the 28-joint disease-activity score for RA patients, and Bath Ankylosing Spondylitis Disease Activity Index for AS patients. Hemagglutination inhibition (HI) antibodies were tested by a standard World Health Organization procedure. Response was defined as ≥4-fold rise in HI antibodies 4 to 6 weeks after vaccination, or seroconversion in patients with a nonprotective baseline level of antibodies (<1/40). Geometric mean titers (GMT) were calculated to assess the immunity of the whole group.

Results

At baseline, RA patients and controls had similar occurrence of protective levels of HI antibodies and GMT, while AS patients had lower levels reflecting lower rates of previous vaccination. Four weeks after vaccination, a significant and similar increase in GMT for each antigen was observed in all groups (P < 0.004) except in the RA-infliximab group, vaccinated 3 weeks after administration of infliximab, in whom the increase in GMT was not significant for H1N1 (P = 0.12) and H3 (P = 0.06). AS patients demonstrated an increase in GMT, independently of the time of vaccination. The percentage of responders was similar in all groups. The response was not affected by variables such as age, gender, methotrexate, or prednisone use. Parameters of disease activity remained unchanged. No adverse effects other than injection site pain were recorded.

Conclusions

Influenza virus vaccine generated a good humoral response in RA and AS patients treated with infliximab.

Section snippets

Subjects

Forty-three consecutive outpatients routinely treated at our department of rheumatology who fulfilled the American College of Rheumatology criteria for RA (9), 18 patients with AS according to the modified New York criteria (10), and 17 healthy hospital personnel matched for age and gender to the RA group participated in the study. Twenty of the 43 RA patients and 18 AS patients had been treated with infliximab at a dosage of 3 mg/kg, for more than 6 months, every 6 to 8 weeks. The remaining 23

Characteristics of Patients and Control Subjects

The RA groups and healthy controls were statistically similar in age and gender and comprised mostly women (Table 1), while AS patients were younger and mostly men. The mean disease duration was 22 years for the RA-infliximab treated patients, 17 years for the RA control group, and 16 years for the AS group. At the time of vaccination, all RA patients were being treated with at least 1 DMARD (Table 2). Eighty-two percent of the noninfliximab RA subjects and 85% of the infliximab RA subjects

Discussion

The current study demonstrated that vaccination against influenza generated a satisfactory humoral response for the 3 antigens tested in RA and AS, including patients treated with infliximab. When the timing of vaccination was studied, a trend toward lower immunity was observed in RA patients vaccinated 3 weeks after the infusion of infliximab as compared with those vaccinated on the day of infliximab treatment. The humoral response was not affected by the different clinical and demographic

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