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Immune response to influenza vaccination in rheumatoid arthritis patients taking methotrexate appears to depend most on stopping the next two weekly doses of the drug rather than any effect from the timing of the last dose, new research concludes.
The new finding, reported in Annals of the Rheumatic Diseases, stems from a post hoc analysis of a randomized, controlled trial that Jin Kyun Park, MD, of Seoul (Korea) National University, and his colleagues had conducted earlier on immune response when patients stopped methotrexate for either 2 or 4 weeks after vaccination. While the main endpoint of that study showed no difference in the improvement in vaccine response with either stopping methotrexate for 2 or 4 weeks and no increase in disease activity with stopping for 2 weeks, it was unclear whether the timing of the last dose mattered when stopping for 2 weeks.
In a bid to identify the optimal time between the last dose of methotrexate and administration of a flu vaccine, Dr. Park and his colleagues conducted a post hoc analysis of the trial, which involved 316 patients with RA receiving methotrexate for 6 weeks or longer to continue (n = 156) or to hold methotrexate (n = 160) for 2 weeks after receiving a quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria.
The study authors defined a positive vaccine response as a fourfold or greater increase in hemagglutination inhibition (HI) antibody titer. A satisfactory vaccine response was a positive response to two or more of four vaccine antigens.
Patients who stopped taking methotrexate were divided into eight subgroups according to the number of days between their last dose and their vaccination.
The research team reported that response to vaccine, fold increase in HI antibody titers, and postvaccination seroprotection rates were not associated with the time between the last methotrexate dose and the time of vaccination.
However, they conceded that “the absence of impact of the number of days between the last methotrexate dose and vaccination could be due to the small patient numbers in eight subgroups.”
Vaccine response also did not differ between patients who received the influenza vaccination within 3 days of the last methotrexate dose (n = 65) and those who received it between 4-7 days of the last methotrexate dose (n = 95).
Furthermore, RA disease activity, seropositivity, or use of conventional or biologic disease-modifying antirheumatic drugs did not have an impact on methotrexate discontinuation.
The authors concluded that vaccinations could be given irrespective of the time of the last methotrexate dose, and patients should be advised to skip two weekly doses following vaccination.
“This supports the notion that the effects of methotrexate on humeral immunity occur rapidly, despite the delayed effects on arthritis; therefore, the absence of methotrexate during the first 2 weeks postvaccination is critical for humoral immunity,” they wrote.
The study was sponsored by GC Pharma. One author disclosed serving as a consultant to Pfizer and receiving research grants from GC Pharma and Hanmi Pharma.
SOURCE: Park JK et al. Ann Rheum Dis. 2019 Mar 23. doi: 10.1136/annrheumdis-2019-215187.
Immune response to influenza vaccination in rheumatoid arthritis patients taking methotrexate appears to depend most on stopping the next two weekly doses of the drug rather than any effect from the timing of the last dose, new research concludes.
The new finding, reported in Annals of the Rheumatic Diseases, stems from a post hoc analysis of a randomized, controlled trial that Jin Kyun Park, MD, of Seoul (Korea) National University, and his colleagues had conducted earlier on immune response when patients stopped methotrexate for either 2 or 4 weeks after vaccination. While the main endpoint of that study showed no difference in the improvement in vaccine response with either stopping methotrexate for 2 or 4 weeks and no increase in disease activity with stopping for 2 weeks, it was unclear whether the timing of the last dose mattered when stopping for 2 weeks.
In a bid to identify the optimal time between the last dose of methotrexate and administration of a flu vaccine, Dr. Park and his colleagues conducted a post hoc analysis of the trial, which involved 316 patients with RA receiving methotrexate for 6 weeks or longer to continue (n = 156) or to hold methotrexate (n = 160) for 2 weeks after receiving a quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria.
The study authors defined a positive vaccine response as a fourfold or greater increase in hemagglutination inhibition (HI) antibody titer. A satisfactory vaccine response was a positive response to two or more of four vaccine antigens.
Patients who stopped taking methotrexate were divided into eight subgroups according to the number of days between their last dose and their vaccination.
The research team reported that response to vaccine, fold increase in HI antibody titers, and postvaccination seroprotection rates were not associated with the time between the last methotrexate dose and the time of vaccination.
However, they conceded that “the absence of impact of the number of days between the last methotrexate dose and vaccination could be due to the small patient numbers in eight subgroups.”
Vaccine response also did not differ between patients who received the influenza vaccination within 3 days of the last methotrexate dose (n = 65) and those who received it between 4-7 days of the last methotrexate dose (n = 95).
Furthermore, RA disease activity, seropositivity, or use of conventional or biologic disease-modifying antirheumatic drugs did not have an impact on methotrexate discontinuation.
The authors concluded that vaccinations could be given irrespective of the time of the last methotrexate dose, and patients should be advised to skip two weekly doses following vaccination.
“This supports the notion that the effects of methotrexate on humeral immunity occur rapidly, despite the delayed effects on arthritis; therefore, the absence of methotrexate during the first 2 weeks postvaccination is critical for humoral immunity,” they wrote.
The study was sponsored by GC Pharma. One author disclosed serving as a consultant to Pfizer and receiving research grants from GC Pharma and Hanmi Pharma.
SOURCE: Park JK et al. Ann Rheum Dis. 2019 Mar 23. doi: 10.1136/annrheumdis-2019-215187.
Immune response to influenza vaccination in rheumatoid arthritis patients taking methotrexate appears to depend most on stopping the next two weekly doses of the drug rather than any effect from the timing of the last dose, new research concludes.
The new finding, reported in Annals of the Rheumatic Diseases, stems from a post hoc analysis of a randomized, controlled trial that Jin Kyun Park, MD, of Seoul (Korea) National University, and his colleagues had conducted earlier on immune response when patients stopped methotrexate for either 2 or 4 weeks after vaccination. While the main endpoint of that study showed no difference in the improvement in vaccine response with either stopping methotrexate for 2 or 4 weeks and no increase in disease activity with stopping for 2 weeks, it was unclear whether the timing of the last dose mattered when stopping for 2 weeks.
In a bid to identify the optimal time between the last dose of methotrexate and administration of a flu vaccine, Dr. Park and his colleagues conducted a post hoc analysis of the trial, which involved 316 patients with RA receiving methotrexate for 6 weeks or longer to continue (n = 156) or to hold methotrexate (n = 160) for 2 weeks after receiving a quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria.
The study authors defined a positive vaccine response as a fourfold or greater increase in hemagglutination inhibition (HI) antibody titer. A satisfactory vaccine response was a positive response to two or more of four vaccine antigens.
Patients who stopped taking methotrexate were divided into eight subgroups according to the number of days between their last dose and their vaccination.
The research team reported that response to vaccine, fold increase in HI antibody titers, and postvaccination seroprotection rates were not associated with the time between the last methotrexate dose and the time of vaccination.
However, they conceded that “the absence of impact of the number of days between the last methotrexate dose and vaccination could be due to the small patient numbers in eight subgroups.”
Vaccine response also did not differ between patients who received the influenza vaccination within 3 days of the last methotrexate dose (n = 65) and those who received it between 4-7 days of the last methotrexate dose (n = 95).
Furthermore, RA disease activity, seropositivity, or use of conventional or biologic disease-modifying antirheumatic drugs did not have an impact on methotrexate discontinuation.
The authors concluded that vaccinations could be given irrespective of the time of the last methotrexate dose, and patients should be advised to skip two weekly doses following vaccination.
“This supports the notion that the effects of methotrexate on humeral immunity occur rapidly, despite the delayed effects on arthritis; therefore, the absence of methotrexate during the first 2 weeks postvaccination is critical for humoral immunity,” they wrote.
The study was sponsored by GC Pharma. One author disclosed serving as a consultant to Pfizer and receiving research grants from GC Pharma and Hanmi Pharma.
SOURCE: Park JK et al. Ann Rheum Dis. 2019 Mar 23. doi: 10.1136/annrheumdis-2019-215187.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Response to vaccine, fold increase in HI antibody titers, and postvaccination seroprotection rates were not associated with the time between the last methotrexate dose and the time of vaccination.
Study details: A post hoc analysis of a randomized, controlled trial involving 316 patients with rheumatoid arthritis who continued or stopped methotrexate for 2 weeks following influenza vaccination.
Disclosures: The study was sponsored by GC Pharma. One author disclosed serving as a consultant to Pfizer and receiving research grants from GC Pharma and Hanmi Pharma.
Source: Park JK et al. Ann Rheum Dis. 2019 Mar 23. doi: 10.1136/annrheumdis-2019-215187