Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: A prospective, open-label, parallel-cohort, single-center study

Abstract

Objective. To identify the determinants of antibody responses to adjuvanted split influenza A (H1N1) vaccines in patients with inflammatory rheumatic diseases.Methods. One hundred seventy-three patients (82 with rheumatoid arthritis, 45 with spondylarthritis, and 46 with other inflammatory rheumatic diseases) and 138 control subjects were enrolled in this prospective single-center study. Controls received 1 dose of adjuvanted influenza A/09/H1N1 vaccine, and patients received 2 doses of the vaccine. Antibody responses were measured by hemagglutination inhibition assay before and 3-4 weeks after each dose. Geometric mean titers (GMTs) and rates of seroprotection (GMT >40) were calculated. A comprehensive medical questionnaire was used to identify the determinants of vaccine responses and adverse events.Results. Baseline influenza A/09/H1N1 antibody levels were low in patients and controls (seroprotection rates 14.8% and 14.2%, respectively). A significant response to dose 1 was observed in both groups. However, the GMT and the seroprotection rate remained significantly lower in patients (GMT 146 versus 340, seroprotection rate 74.6% versus 87%; both P < 0.001). The second dose markedly increased antibody titers in patients, with achievement of a similar GMT and seroprotection rate as elicited with a single dose in healthy controls. By multivariate regression analysis, increasing age, use of disease-modifying antirheumatic drugs (DMARDs) (except hydroxychloroquine and sulfasalazine), and recent (within 3 months) B cell depletion treatment were identified as the main determinants of vaccine responses; tumor necrosis factor ␣ antagonist treatment was not identified as a major determinant. Immunization was well tolerated, without any adverse effect on disease activity.Conclusion. DMARDs exert distinct influences on influenza vaccine responses in patients with inflammatory rheumatic diseases. Two doses of adjuvanted vaccine were necessary and sufficient to elicit responses in patients similar to those achieved with 1 dose in healthy controls.

Effect of Methotrexate, Anti–Tumor Necrosis Factor α, and Rituximab on the Immune Response to Influenza and Pneumococcal Vaccines in Patients With Rheumatoid Arthritis: A Systematic Review and Meta‐Analysis

“…In their study, Kapetanovic et al found similar or better seroconversion rates after influenza vaccination in a group of 62 patients receiving anti-TNF␣ without MTX (50% for H1N1, 51.6% for H3N2, and 58.1% for B) than in 18 healthy controls (50% for H1N1, 44.4% for H3N2, and 5.6% for B) (17). Moreover, in 3 studies that could not be included in the meta-analysis because the population included a combination of several inflammatory diseases, anti-TNF␣ did not reduce vaccine responsiveness (28,29,33).…”

“…Injection of a second dose, 1 month after the first dose, of pandemic H1N1 influenza vaccine was found to be more efficient than an injection of a single dose in patients with rheumatic inflammatory diseases (29). However, additional studies assessing the need of second booster doses in RA patients receiving treatments responsible for an impaired immune response are needed.…”

Vaccinations for rheumatoid arthritis

“…HI titers of 1:40 or greater have been shown to be protective against influenza in the general population [9]. Most of the studies evaluated suggest that RA patients using methotrexate and/or anti-TNF therapy (adalimumab, etanercept, infliximab) achieve an acceptable humoral response, although their response is lower than in healthy controls [10][11][12][13][14][15][16][17][18]. A recent study, in 2012, involving RA patients receiving tocilizumab, methotrexate (MTX) or the combination of the two suggest that there was no decreased effects of TCZ, and post-vaccination GMTs increased significantly for all strains of the influenza vaccine [19].…”

Vaccination in Rheumatology: Current Aspects

“…В боль-шинстве работ показано, что у больных РА, получавших метотрексат (МТ) и/или ингибиторы фактора некроза опу-холи α (иФНОα), достигаются приемлемые уровни гумо-рального поствакцинального ответа, хотя и более низкие, чем в контроле [24][25][26][27][28][29][30][31][32].…”