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ACR 2017 | Daily Highlights
Temporary Methotrexate Discontinuation for 2 Weeks Improves Immunogenicity of Seasonal Influenza Vaccination in Patients with Rheumatoid Arthritis: A Randomized Clinical Trial
Authors: Jin Kyun Park1, Kichul Shin2, You-Jung Ha3, Yun Jong Lee4, Eun Young Lee5, Yeong Wook Song6, Yunhee Choi7, Kevin Winthrop8 and Eun Bong Lee9, 1Division of Rheumatology, Seoul National University Hospital, Seoul, Korea, Republic of (South), 2Kyungnam villa #102, Division of Rheumatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea, Republic of (South), 3Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 4Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic of (South), 5Division of Rheumatology, Department of Internal Medicine, Seoul National University, Seoul, Korea, Republic of (South), 6Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Seoul National University, Seoul, Korea, The Republic of, Seoul, Korea, Republic of (South), 7Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University College of Medicine, Seoul, Korea, Republic of (South), 8Oregon Health & Science University, Portland, OR, 9Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea, Republic of (South)
Methotrexate (MTX), a widely used immune-suppressive agent, decreases vaccine response in patients with rheumatoid arthritis (RA). We investigated whether a temporary MTX discontinuation for 2 weeks after vaccination improves the efficacy of seasonal influenza vaccination in RA patients.
In this prospective, multicenter, randomized, parallel-group trial, RA patients taking stable dose of MTX were randomly assigned at a ratio of 1:1 to continue MTX (MTX-continue group) or to suspend MTX for 2 weeks after vaccination (MTX-hold group). All participants were vaccinated with seasonal quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria. The primary outcome was frequency of satisfactory vaccine response, defined as ?4-fold increase in hemaglutination inhibition (HI) antibody titer at 4 weeks after vaccination against ?2 of 4 vaccine strains. Secondary endpoints included seroprotection rate, fold-change in antibody titers relative to baseline in geometric mean titer (GMT).
We enrolled 320 patients between Oct 7, 2016 and Jan 9, 2017. The modified intention-to-treat population consisted of 316 patients (156 in the MTX-continue group and 160 in the MTX-hold group). Higher proportion of patients in MTX-hold group achieved satisfactory vaccine response compared to MTX-continue group (75.5% vs. 54.5%, p < 0.001) (Figure). Post-vaccination seroprotection rate was higher for all 4 antigens in the MTX-hold group than the MTX-continue group (H1N1: 75.6% vs. 86.3%, p=0.016; H3N2: 62.2% vs.78.1%, p=0.002; B-Yamagata: 74.4% vs. 88.1%, p=0.002; B-Victoria: 60.9% vs. 75.6%, p= 0.005). Similarly, the MTX-hold group achieved higher fold increase of post-vaccination HI antibody titer in GMT [95% CI] for each antigen (H1N1: 4.6 [3.7- 5.7] vs. 6.7 [5.4 – 8.3], p=0.017; H3N2: 4.3 [3.5 – 5.3] vs. 8.0 [6.4 – 9.9], p <0.001; B-Yamagata: 3.1 [2.6 – 3.8] vs. 5.6 [4.7- 6.6], p<0.001; B-Victoria: 2.9 [2.4- 3.4] vs. 5.7 [4.9 – 6.7], p<0.001). Vaccine was well tolerated. Disease activity after vaccination did not differ between both groups.
Temporary MTX discontinuation for 2 weeks after vaccination improves the immunogenicity of seasonal influenza vaccination in RA patients without increasing RA disease activity.
Trial registration: [www.clinicaltrials.gov, protocol number NCT02897011].
J. K. Park, None; K. Shin, None; Y. J. Ha, None; Y. J. Lee, None; E. Y. Lee, None; Y. W. Song, None; Y. Choi, None; K. Winthrop, Pfizer, UCB, Abbvie, Eli Lilly and Company, Amgen, BMS, 5,Pfizer, BMS, 2; E. B. Lee, Green Cross Corp, 2,Pfizer Inc, 5.
This Korean trial has examined an important practical question, namely what to do with common antirheumatic drugs when vaccinating our patients. It was known from previous studies, conducted among others in Switzerland, that methotrexate (MTX) decreases the immunogenic response to common vaccines, like the flu vaccine, and it was suggested that patients on MTX should get two separate vaccinations instead of one. In this trial, the authors explore another pragmatic approach and proposed to temporarily discontinue MTX for 2 weeks after vaccination. They show that a higher proportion of patients randomized to the ‘MTX-hold arm’ achieved a sufficient vaccine response compared to patients in the ‘MTX-continue arm’ (75.5% vs. 54.5%, p < 0.001). Patients in the ‘MTX-hold arm’ also achieved statistically significant higher titers of anti-flu antibodies. No significant difference in number of flares occurred due to the 2 week temporary hold of MTX, which makes this approach a practical and feasible approach for our patients on MTX.
Prof. Dr. Axel Finckh
Geneva University Hospital