Efficacy, immunogenicity and safety of monovalent (H1N1) pandemic influenza vaccination in patients with AIIRD (October 2009–August 2018)
| First author +ref. | Year | Study design | No. cases | Efficacy | Immunogenicity | Safety | Influence of IS on eff./ imm. | LoE | ||
| Eff. | Imm. | Saf. | ||||||||
| Milanetti41
Both seasonal and pandemic, adj. (MF59) | 2014 | Cohort | 30 RA 13 HC | – | No difference | More mild AE in patients | No effect of anti-TNF or ABA | – | 2b | 4 |
| Kapetanovic62
Adj. (AS03) | 2014 | Cohort | 50 RA-MTX 38 RA-anti-TNF 53 RA-anti-TNF+MTX 5 RA-ABA- 10 RA-RTX 2 RA TCZ 41 SpA-anti-TNF 51 SpA-anti-TNF+MTX Two doses in 58% | – | Reduced in RA-RTX Increased in SpA-anti-TNF Increased after two doses, except for RA-MTX and RA- RTX | One pneumonia 8.2% of patients reported that vaccination influenced their rheumatic disease | Reduced on RTX and ABA (only five pts) | – | 2b | 4 |
| Ribeiro82
Non-adj. Subanalysis of 58 | 2013 | Cohort | 11 RA-ABA 33 RA-MTX DC 55 HC | – | Reduced in RA-ABA | No difference AE. | Reduced on ABA | – | 2b | 4 |
| Adler59
AS03 adjuvanted | 2012 | Cohort | 47 RA 59 SpA 15 vasculitis 28 CTD 40 HC | – | Reduced in patients (but not in SpA and CTD) | No difference in AE. Increase disease activity in 32 patients | Reduced on ABA, RTX (n=8) and MTX 2 responders in RTX group: 1 and 3 mo after RTX | – | 2b | 4 |
| França60
Non-adj. | 2012 | Cohort | 41 RA-anti-TNF 79 SpA-anti-TNF 41 RA-DC 75 SpA-DC 117 HC | – | Reduced in SpA-anti-TNF but not for etanercept | More mild systemic AE in patients on anti- TNF | Reduced on MTX (RA). Reduced on anti-TNF (SpA) (except etanercept) | – | 2b | 4 |
| Iwamoto61
Mostly non-adj. | 2012 | Cohort | 89 RA 14 HC | – | Reduced (non-significant) in RA Seroprotection 55.1% | 1 facial palsy | Lower (non-significant) on biologics | – | 2b | 5 |
| Saad54
Non-adj. | 2011 | Cohort | 1668 AIIRD* 234 HC | – | Reduced in AIIRD versus HC Reduced in SLE and RA | Overall stable disease | No | – | 2b | 4 |
| Gabay55
Adj. (AS03) | 2011 | Cohort | 82 RA 45 SpA 46 other AIIRD 138 HC | – | Reduced in patients No difference after two doses in patients (seroprotection after 1 and 2 doses 75% and 85%, respectively) | Overall stable disease | Reduced on DMARDs and within 3 mo. after B cell depletion | – | 2b | 4 |
| Miraglia56
Non-adj. | 2011 | Cohort | 1152 Immunocompromised†: 260 RA 83 JIA | – | Seroprotection in 61.5% of patients with RA and in 85.5% of patients with JIA | Mild systemic AE in more than 20% of RA and JIA | – | – | 2b | 4 |
| Elkayam57
Adj. (MF59) | 2011 | Cohort | 41 RA 21 SLE 17 PsA 15 AS 25 HC | – | Reduced in patients with RA/PsA Seroprotection in 60%–76% of patients | Overall stable disease | Reduced on leflunomide and infliximab | – | 2b | 4 |
| Ribeiro58
Non-adj. | 2011 | Cohort | 340 RA 234 HC | – | Reduced in RA No influence of disease activity | More local AE in HC. More mild systemic AE in RA | Reduced on MTX | – | 2b | 2b |
| Müller206
Adj. (AS03) | 2013 | Case series | 16 RA+SjS | – | SC in B cell depleted: 22%, non-depleted: 57% | More influenza-like symptoms in B cell depleted patients | Low response with RTX | – | 4 | 5 |
| Borba64
Non-adj. | 2012 | Cohort | 555 SLE 170 HC | – | Reduced in SLE with therapy (except for antimalarials) No difference in HC and SLE without therapy | Overall stable disease | Reduced for steroids and IS Restored when using concomitant antimalarials | – | 2b | 2b |
| Kostianovsky52
Both seasonal and pandemic, non-adj. | 2012 | Cohort | 74 systemic vasculitis 32 SSc 29 SLE 23 SjS 28 other AIIRD | – | No difference | 19 flares | No | – | 4 | 4 |
| Lu63
Non-adj. | 2011 | Cohort | 21 SLE 15 HC | – | No difference | Changes in autoantibody levels Overall stable clinical disease activity one flare | No | – | 2b | 4 |
| Urowitz207
Both adj. and non-adj. | 2011 | Cohort | 103 SLE: 51 adj. 52 non-adj. | – | – | No difference Overall stable disease | – | – | – | 2b |
| Mathian69
Non-adj. | 2011 | Cohort | 111 SLE | – | Increased after booster vaccination (seroprotection after 1 and 2 doses 67% and 80%, respectively) | No severe AE Overall stable disease | Reduced on IS | – | 2b | 4 |
| Brauner67 | 2017 | Cohort | 14 SjS 18 HC | Higher levels of influenza-specific IgG in patients, and higher avidity | Antibody titres to non-influenza (incl autoantigens Ro/SSA and La/SSB) antigen increased in patients, but not in HC. | – | – | 4 | 4 | |
| Sampaio-Barros68 | 2017 | Cohort | 92 SSc 92 HC | – | Higher GMT SSc Comparable SP and SC | No difference in AE No SAE | No | – | 2b | 4 |
| De Medeiros208
Non-adj. | 2014 | Cohort | 45 PAPS 33 HC | – | – | No change in overall frequencies of autoantibodies | – | – | – | 2b |
| Miossi66
Non-adj. | 2013 | Cohort | 69 MCTD 69 HC | – | No difference | Overall stable disease | No | – | 2b | 4 |
| Shinjo65
Non-adj. | 2012 | Cohort | 37 DM +21 PM 116 HC | – | No difference | No difference Overall stable disease | No | – | 2b | 4 |
The table is structured as follows: First studies in RA, then systemic lupus erythematosus (SLE) followed by other autoimmune inflammatory rheumatic diseases (AIIRD). Within this organisation, presented in order of publication year.
*Group consisted of patients with SLE (n=572), RA (n=343), psoriatic arthritis (n=101), ankylosing spondylitis (n=152), Behçet’s disease (n=85), dermatomyositis (n=45), systemic sclerosis (n=127), mixed connective tissue disease (n=69), primary antiphospholipid syndrome (n=54), primary Sjögren’s syndrome (n=36), Takayasu’s arteritis (n=30), polymyositis (n=28), granulomatosis with polyangiitis (n=26).
†Group consisted of patients with cancer (n=319), RA (n=260), HIV infection (n=256), kidney transplant recipients (n=85), juvenile idiopathic arthritis (n=83) and elderly persons (n=149).
ABA, abatacept; adj., adjuvanted; AS, ankylosing spondylitis; AS, adjuvant system; DC, disease control; DM, dermatomyositis; DMARD, disease-modifying antirheumatic drug; eff., efficacy; GMT, geometrical mean titre; HC, healthy controls; imm, immunogenicity; IS, immunosuppressives; JIA, juvenile idiopathic arthritis; LoE, level of evidence; (M)CTD, (mixed) connective tissue disease; mo., months; MTX, methotrexate; No., number; PAPS, primary antiphospholipid syndrome; PM, polymyositis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; ref., reference; RTX, rituximab; (S)AE, (serious) adverse event(s); saf., safety; SC, seroconversion; SjS, Sjögren’s syndrome; SP, seroprotection; SpA, spondyloarthropathy; SSc, systemic sclerosis; TCZ, tocilizumab; TNF, tumor necrosis factor.