Ann Rheum Dis. 2018;77(6):898-904.

Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial.

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제1저자 박진균 · 교신저자 이은봉

PMID 29572291 PMC5965360 DOI 10.1136/annrheumdis-2018-213222 IF 24 류마티스내과

소속 (5)

Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.
Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA.

Abstract

OBJECTIVE To determine whether a 2-week methotrexate (MTX) discontinuation after vaccination improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA).

METHODS In this prospective randomised parallel-group multicentre study, patients with RA on stable dose of MTX were randomly assigned at a ratio of 1:1 to continue MTX or to hold MTX for 2 weeks after 2016-2017 quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B-Yamagata and B-Victoria. The primary outcome was frequency of satisfactory vaccine response, defined as greater than or equal to fourfold increase of haemagglutination inhibition (HI) antibody titre at 4 weeks after vaccination against ≥2 of four vaccine strains. Secondary endpoints included seroprotection (ie, HI titre ≥1:40) rate, fold change in antibody titres.

RESULTS The modified intention-to-treat population included 156 patients in the MTX-continue group and 160 patients in the MTX-hold group. More patients in MTX-hold group achieved satisfactory vaccine response than the MTX-continue group (75.5% vs 54.5%, p<0.001). Seroprotection rate was higher in the MTX-hold group than the MTX-continue group for all four antigens (H1N1: difference 10.7%, 95% CI 2.0% to 19.3%; H3N2: difference 15.9%, 95% CI 5.9% to 26.0%; B-Yamagata: difference13.7%, 95% CI 5.2% to 22.4%; B-Victoria: difference 14.7%, 95% CI 4.5% to 25.0%). The MTX-hold group showed higher fold increase in their antibody titres against all four influenza antigens (all p<0.05). Change in disease activity was similar between groups.

CONCLUSIONS A temporary MTX discontinuation for 2 weeks after vaccination improves the immunogenicity of seasonal influenza vaccination in patients with RA without increasing RA disease activity.

TRIAL REGISTRATION NCT02897011.

Keywords

discontinuationinfluenzamethotrexaterheumatoid arthritisvaccination

Figures

**Figure 1** Patient flow. MTX, methotrexate; mITT, modified intention-to-treat.

**Figure 2** Frequency of vaccination responses to the influenza antigens. Satisfactory vaccine response, defined as greater than or equal to four fold increase of haemagglutination inhibition antibody titre at 4 weeks after vaccination against ≥2 of 4 vaccine strains (A) and against ≥1 of 4, ≥3 of 4 and 4 of 4 vaccine strains (B). Numbers in the bars indicate the percentage of satisfactory responders. Error bar represents 95% CI. P values were generated by Χ² test. MTX, methotrexate.

**Figure 3** Impact of baseline methotrexate (MTX) dose on vaccination responses to the influenza antigens. Log-transformed fold change in antibody titre against each vaccine strain relative to baseline was depicted according to the baseline MTX dose per week (mg/week). Bar and whiskers represent mean and SD, respectively. P values were generated by t-test.

그림 출처: PubMed Central 공개 논문 (PMC5965360)

Conflict of interest statement

Competing interests: EBL has acted as a consultant to Pfizer and received research grants from Green Cross Corporation and Hanmi Pharm.

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