Background/Purpose:

Vaccines against influenza and streptococcus pneumonia are currently recommended for patients with rheumatoid arthritis (RA). This meta-analysis assesses current literature data on the impact of methotrexate (MTX), anti-TNF or rituximab (RTX) on the humoral response to pneumococcal and influenza vaccines in RA patients.

Methods:

Data sources were Medline, Embase and Cochrane databases and ACR 2011 abstracts. To be included, studies had to contain a group of RA patients treated with MTX, anti-TNF or RTX and a control group of RA patients without the treatment of interest. Both groups had to receive either pneumococcal or influenza vaccine. Results had to show rates of responders based on the antibody response ratio, corresponding to the level of antibodies measured at 1 month following vaccination as numerator and the level of antibodies at vaccination as denominator, for pneumococcal serotypes 6B and 23F or one of the 3 strains of influenza virus: H1N1, H3N2 and B. Out of 59 potentially relevant studies, 11 met inclusion criteria. Odds-ratios and their 95% confidence intervals were pooled using the generic inverse variance method. The heterogeneity between studies was assessed using the Cochran’s Q-test and the I²value, and a random effect model was performed if necessary. All the analyses were realized with the RevMan software 5.1 version. A significant statistical threshold of 0.05 was used.

Results: 

Following pneumococcal vaccination: response was reduced in patients treated with anti-TNF + MTX compared to those treated with anti-TNF not combined with MTX (pooled odds-ratio (OR) = 0.58; 95% confidence interval (CI) 0.36-0.94; p=0.03 for 23F and 0.33; 95% CI 0.20-0.54; p<0.0001 for 6B). Rates of responders were similar in patients under MTX alone and those treated with  MTX +anti-TNF (OR = 1.21; 95% CI 0.83-1.75 for 23F and 0.96; 95% CI 0.57-1.59 for 6B). The immune response was lower in patients treated with RTX, combined in most cases with MTX, than in patients under MTX as monotherapy (OR = 0.22; 95% CI 0.11-0.47; p<0.0001 for 23F and 0.25; 95% CI 0.11-0.58; p=0,001 for 6B).

Following influenza vaccination:proportion of responders was not different between patients treated with MTX and those not treated with MTX (OR= 1.36 ; 95%CI 0.69-2.68 for H1N1, 1.33; 95%CI 0.70-2.53 for H3N2, 1.28; 95%CI 0.64-2.56 for B). Response was decreased in patients under PBO+MTX versus patients under PBO not combined with MTX (OR for responders to at least 2 strains = 0.35; 95% CI 0.18-0.66; p=0.001). Patients treated with anti-TNF with or without MTX had same responders rates than patients whose treatment did not include anti-TNF (OR for responders to at least 2 strains = 0.42; 95% CI 0.17-1.09). Patients under RTX in monotherapy or in combination with DMARDs had a disminished humoral response compared to patients treated with DMARDs without RTX, significance being reached for H3N2 and B (OR = 0.11; 95% CI 0.04-0.31; p<0.0001 and 0.29; 95% CI 0.10-0.81; p=0.02).

Conclusion:

Immune response to both vaccines is reduced with RTX but not with anti-TNF. MTX decreased immunogenicity of pneumococcal vaccine whereas results about influenza vaccine are less homogeneous but suggest an impairment of the response due to MTX therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/meta-analysis-influence-of-methotrexate-anti-tnf-and-rituximab-on-the-immune-response-to-influenza-and-pneumococcal-vaccines-in-patients-with-rheumatoid-arthritis/