Sujith Subesinghe1,2, Katie Bechman3,4, Andrew I Rutherford3,4, David Goldblatt3,4, James B Galloway3,4. 1. From the Department of Academic Rheumatology, King's College London, Weston Education Centre; Institute of Child Health, University College London, London, UK. ssubesinghe@nhs.net. 2. S. Subesinghe, BSc, MBBS, MSc, MRCP, Clinical Research Fellow and Rheumatology Registrar, Department of Academic Rheumatology, King's College London, Weston Education Centre; K. Bechman, BSc, MBBS, MRCP, Clinical Research Fellow and Rheumatology Registrar, Department of Academic Rheumatology, King's College London, Weston Education Centre; A.I. Rutherford, BSc, MBBS, MSc, MRCP, Clinical Research Fellow and Rheumatology Registrar, Department of Academic Rheumatology, King's College London, Weston Education Centre; D. Goldblatt, MBChB, FRCPCH, FRCP, PhD, Prof, Vaccinology and Immunology, Institute of Child Health, University College London; J.B. Galloway, MBChB, MSc, CHP, FRCP, PhD, FAcadMedEd, Senior Lecturer and Honorary Consultant Rheumatologist, Department of Academic Rheumatology, King's College London, Weston Education Centre. ssubesinghe@nhs.net. 3. From the Department of Academic Rheumatology, King's College London, Weston Education Centre; Institute of Child Health, University College London, London, UK. 4. S. Subesinghe, BSc, MBBS, MSc, MRCP, Clinical Research Fellow and Rheumatology Registrar, Department of Academic Rheumatology, King's College London, Weston Education Centre; K. Bechman, BSc, MBBS, MRCP, Clinical Research Fellow and Rheumatology Registrar, Department of Academic Rheumatology, King's College London, Weston Education Centre; A.I. Rutherford, BSc, MBBS, MSc, MRCP, Clinical Research Fellow and Rheumatology Registrar, Department of Academic Rheumatology, King's College London, Weston Education Centre; D. Goldblatt, MBChB, FRCPCH, FRCP, PhD, Prof, Vaccinology and Immunology, Institute of Child Health, University College London; J.B. Galloway, MBChB, MSc, CHP, FRCP, PhD, FAcadMedEd, Senior Lecturer and Honorary Consultant Rheumatologist, Department of Academic Rheumatology, King's College London, Weston Education Centre.
Abstract
OBJECTIVE: Vaccination is a key strategy to reduce infection risk in patients with rheumatoid arthritis (RA) and is advocated in internationally recognized rheumatology society guidelines. The aim was to evaluate to the effect of antirheumatic drugs on influenza and pneumococcal vaccine immunogenicity. METHODS: We conducted a systematic literature review and metaanalysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunit vaccines) and pneumococcal (23-valent pneumococcal polysaccharide vaccine, 7- and 13-valent pneumococcal conjugated vaccines) vaccination in adult patients with RA treated with antirheumatic drugs. Vaccine immunogenicity was assessed by seroprotection rates measured 3 to 6 weeks postimmunization. Risk ratios (RR) and 95% CI were pooled. RESULTS: Nine studies were included in the metaanalysis (7 studies investigating antirheumatic drug exposures and influenza humoral response, 2 studies investigating pneumococcal vaccine response). Influenza vaccine responses to all subunit strains (H1N1, H3N2, B strain) were preserved with methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) drug exposure. MTX but not TNFi drug exposure was associated with reduced 6B and 23F serotype pneumococcal vaccine response (RR 0.42, 95% CI 0.28-0.63 vs RR 0.98, 95% CI 0.58-1.67); however, limited data were available to draw any firm conclusions. Combination of MTX with tocilizumab or tofacitinib was associated with reduced pneumococcal and influenza vaccine responses. CONCLUSION: Antirheumatic drugs may limit humoral responses to vaccination as evidenced by pneumococcal responses with MTX exposure; however, they are safe and should not preclude immunization against vaccine-preventable disease. Vaccination should be considered in all patients with RA and encouraged as part of routine care. (Systematic review registration number: PROSPERO 2016: CRD42016048093.).
OBJECTIVE: Vaccination is a key strategy to reduce infection risk in patients with rheumatoid arthritis (RA) and is advocated in internationally recognized rheumatology society guidelines. The aim was to evaluate to the effect of antirheumatic drugs on influenza and pneumococcal vaccine immunogenicity. METHODS: We conducted a systematic literature review and metaanalysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunit vaccines) and pneumococcal (23-valent pneumococcalpolysaccharide vaccine, 7- and 13-valent pneumococcal conjugated vaccines) vaccination in adult patients with RA treated with antirheumatic drugs. Vaccine immunogenicity was assessed by seroprotection rates measured 3 to 6 weeks postimmunization. Risk ratios (RR) and 95% CI were pooled. RESULTS: Nine studies were included in the metaanalysis (7 studies investigating antirheumatic drug exposures and influenza humoral response, 2 studies investigating pneumococcal vaccine response). Influenza vaccine responses to all subunit strains (H1N1, H3N2, B strain) were preserved with methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) drug exposure. MTX but not TNFi drug exposure was associated with reduced 6B and 23F serotype pneumococcal vaccine response (RR 0.42, 95% CI 0.28-0.63 vs RR 0.98, 95% CI 0.58-1.67); however, limited data were available to draw any firm conclusions. Combination of MTX with tocilizumab or tofacitinib was associated with reduced pneumococcal and influenza vaccine responses. CONCLUSION: Antirheumatic drugs may limit humoral responses to vaccination as evidenced by pneumococcal responses with MTX exposure; however, they are safe and should not preclude immunization against vaccine-preventable disease. Vaccination should be considered in all patients with RA and encouraged as part of routine care. (Systematic review registration number: PROSPERO 2016: CRD42016048093.).
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