Introduction
Vaccine Immunogenicity in Paediatric Patients With Rheumatic Diseases
Immunogenicity in Relation to Immunosuppressive Drugs
Glucocorticosteroids
Reference | Medication | Vaccine | LoE | Immunogenicity | Safety |
---|---|---|---|---|---|
Glucocorticosteroids | |||||
Kanakoudi-Tsakalidou et al. [25] | 16 GC ≤0.5 mg/kg/day 16 GC ≤0.5 mg/kg/day + MTX 15–20 mg/m2/week 11 GC ≤0.5 mg/kg/day + CY 2.5–3.5 mg/kg/day 6 GC ≤0.5 mg/kg/day + AZA 2–2.5 mg/kg/day 8 GC ≤0.5 mg/kg/day + MTX + CY
Versus 13 ARD without GC (5 MTX, 4 CY, 4 MTX + CY) and 5 HC
| Influenza | 3 | No effect of GC on antibody concentrations or response rate compared to patients without GC. No flu-like symptoms in any of the patients until 6 months after vaccination. | – |
Kasapçopur et al. [26] | 20 GC 6.05 mg (2.5–10 mg/day)
Versus 19 JIA without GC and 41 HC
| HBV | 3 | No effect of GC on antibody concentration (GMT 109.7 IU/ml versus 141.1 IU/ml) or response rate. | No increase in disease activity. |
Kiray et al. [27] | 55 GC 2.5–40 mg/day
Versus 60 JIA without GC
| BCG | 3 | No effect of GC on PPD induration size (3.9 mm versus 4.7 mm) several years after BCG vaccination. PPD positivity rate similar in GC users and nonusers | – |
Lu et al. [28] | 12 GC <2 mg/kg/day Versus 19 non-immunosuppressed IBD
| Influenza | 3 | No effect of GC on seroprotection rate against 3 influenza strains. Higher post vaccination GMT for strain B compared to patients without IS drugs. | No difference in adverse events and disease activity compared to patients without IS drugs. |
Pileggi et al. [17] | 13 GC 0.1–0.7 mg/kg/day All combined with MTX 12–25 mg/m2/week 3 combined with CY 3–3.5 mg/kg/day 1 combined with leflunomide 10 mg/day 1 combined with penicillamine 13 mg/kg/day
Versus 12 ARD without GC
| VZV | 3 | Seroprotection 8/13 patients on GC versus 7/12 patients on MTX monotherapy. | 2/13 patients with GC + MTX + DMARD had mild self-limiting VZV-like rash, compared to 1/12 patient with MTX monotherapy. No increase in disease activity, no increase in medication use. |
Miyamoto et al. [20] | 12 GC 0.2–0.9 mg/kg/day post vaccination
Versus 7 SLE without GCs post vaccination
| MMR DTP | 3 | No effect of GC on established antibody concentrations or seroprotection rate. | – |
Ogimi et al. [29] | 14 GC 0.18 ± 0.17 mg/kg
Versus 36 HC
| Influenza | 3 | Similar anti-influenza antibody concentrations and seroconversion rate as HC. | – |
Aytac et al. [30] | 17 GC mean dose 6.25 mg/day 11 combined with AZA mean dose 100 mg/day 3 combined with MMF mean dose 1000 mg/day 2 combined with HCQ mean dose 200 mg/day 3 without medication
Versus 24 HC
| HBV | 3 | GMT not significantly lowered by GC or AZA; however, large proportion of patients used these medications and a control group was lacking. Not-significant negative correlation between prednisone use and anti-HBs titres. Differences in seroconversion or seroprotection were not reported. | – |
Heijstek et al. [18] | 23 oral GC <20 mg/day median dose 10 mg/day) 5 oral GC ≥20 mg/day 246 NSAID 93 MTX median dose 10 mg/m2/week 24 DMARD 8 anti-TNFα
Versus 2176 HC
| MMR | 3 | No effect of GC at time of sampling on level of antibodies or seroprotection rates several years after vaccination. | – |
Aikawa et al. [31]a
| 54 GC <20 mg/day 36 GC ≥ 20 mg/day 74 MTX 43 AZA 23 cyclosporin 13 MMF 6 leflunomide 3 CY
Versus 92 HC
| Influenza | 3 | No differences in the seroconversion rate, seroprotection rate were seen between treatment groups. Lower GMT were seen in patients who used AZA, MMF or GC, especially in a dose >20 mg, or patients who used GC and IS. | – |
Campos et al. [32] | 92 Antimalarials 43 GC <20 mg/day 40 GC ≥20 mg/day 44 AZA 15 MMF 14 MTX 3 CYC 2 CSP
Versus 102 HC
| Influenza | 3 | Non-seroconversion was associated with a higher prednisone dose in univariate analysis. No effect of medication in multivariate analysis. | – |
Methotrexate | |||||
Kasapçopur et al. [26] | 22 MTX 10 mg/m2/week
Versus 17 without MTX and 41 HC
| HBV | 3 | No effect of MTX on antibody concentration (GMT 114.4 versus 137 IU/ml) or response rate. | No increase in disease activity. |
Heijstek et al. [33] | 49 MTX 7–25 mg/m2/week
Versus 158 JIA without MTX
| MMR | 3 | – | No increase in disease activity. |
Kiray et al. [27] | 73 MTX 3–20 mg/week
Versus 42 JIA without MTX
| BCG | 3 | No effect of MTX on PPD induration size (4.3 versus 3.9 mm) several years after BCG vaccination. PPD positivity rate similar in MTX users and nonusers. | – |
Borte et al. [34] | 5 MTX 10 mg/m2/week 5 MTX 10 mg/m2/week + anti-TNFα 0.4 mg/kg
Versus 22 HC and 5 JIA with MTX 10 mg/m2/week 4 years post MMR
| MMR | 3 | No effect of MTX during vaccination on cellular or humoral immunity. | No increase in disease activity or medication use after MMR booster, irrespective of MTX use. No overt measles, mumps or rubella infection induced by vaccination. |
Woerner et al. [35] | 18 MTX 10 anti-TNFα 8 MTX + anti-TNFα 7 GC <0.5 mg/kg combined with MTX or anti-TNFα
Versus 16 HC
| Influenza | 2b | No significant difference in seroconversion, seroprotection or GMT between treatment groups. No effect of MTX on relative difference between pre- and post vaccination GMT in multivariate analysis. | – |
Aikawa et al. [36]a
| 47 MTX 5–50 mg/week 63 DMARD/IS (prednisone, leflunomide, CYC, SSZ) 16 anti-TNFα
Versus 91 HC
| Influenza | 3 | Seroconverted patients (83.2 %) and non-seroconverted patients (16.8 %) had similar types of therapy and doses of each therapy. | – |
Heijstek et al. [18] | 93 MTX median dose 10 mg/m2/week 23 oral GC <20 mg/day median dose 10 mg/day) 5 oral GC ≥20 mg/day 246 NSAID 24 DMARD 8 anti-TNFα
Versus 2176 HC
| MMR | 3 | No effect of MTX at time of sampling on level of antibodies or seroprotection rates several years after vaccination. | – |
Stoof et al. [22] | 108 MTX 60 biologicals 14 GC
Versus 1527 HC
| MenC | 3 | No effect of MTX on decline of antibody levels over time. | – |
IVIG | |||||
Tacke et al. [37] | 150 IVIG
Versus 92 HC
| MMR | 3 | Seroprotection and GMT reduced until 9 months after IVIG treatment | – |
Biologicals | |||||
Borte et al. [34] | 5 MTX 10 mg/m2/week + anti-TNFα 0.4 mg/kg
Versus 22 HC and 10 JIA without anti-TNFα
| MMR | 3 | No effect of anti-TNFα during vaccination on cellular or humoral immunity. | No increase in disease activity or medication use after MMR booster, irrespective of anti-TNFα. No overt measles, mumps or rubella infection induced by vaccination. |
Lu et al. [28] | 45 anti-TNFα
Versus 19 non-immunosuppressed IBD
| Influenza | 3 | Lower response rate to strain B in patients on anti-TNFα (14 %) compared with patients without IS drugs (39 %). | No difference in adverse events and disease activity compared to patients without IS drugs. |
Lu et al. [38] | 2 anti-TNFα (infliximab) + 6-MP
Versus 4 IBD with 6-MP monotherapy (1.5–2 mg/kg/day) | VZV | 4 | No effect of anti-TNFα during vaccination on seroprotection rate (100 %). Proper control group is lacking. | No serious adverse events after primary/booster VZV vaccination, despite anti-TNFα usage. |
Farmaki et al. [39] | 31 MTX/CY ± GC + anti-TNFα
Versus 32 MTX/CY ± GC
| PCV7 | 2B | Lower antibody concentrations against 3/7 serotypes in patients on anti-TNFα, but similar response and protection rate. | Mild adverse events in 6/31 patients on anti-TNFα versus 5/32 patients without anti-TNFα. |
Erguven et al. [40] | 4 anti-TNFα
Versus 43 JIA without anti-TNFα but with GC and/or DMARD and 67 HC
| HAV | 3 | 4 patients on anti-TNFα negative for anti-HAV antibodies after vaccination. 100 % response rate in all other patients and HC. | No adverse events. No increase in disease activity. |
Woerner et al. [35] | 10 anti-TNFα 8 MTX + anti-TNFα 18 MTX 7 GC <0.5 mg/kg combined with MTX or anti-TNFα
Versus 16 HC
| Influenza | 3 | No significant difference in seroconversion, seroprotection or GMT between treatment groups. Analysis of the effect of biologicals on relative difference between pre- and post vaccination GMT in multivariate analysis showed a trend towards a lower relative change. | – |
Dell’Era et al. [41] | 30 DMARD (unspecified) 18 DMARD + MTX mean dose 10 ± 1.4 mg/m2/week 30 anti-TNFα 14 anti-TNFα + MTX 10 ± 1.4 mg/m2/week
Versus 30 HC
| Influenza | 3 | Patients using anti-TNFα had significantly lower seroconversion rates and seroprotection rates against strain B, a significantly lower GMT against H1N1 and B, and showed a more rapid decline of GMT over time. | – |
Toplak et al. [24] | 7 DMARD + GC (<10 mg/day) 4 anti-TNFα 3 leflunomide 2 sulphasalazine
Versus 18 patients without therapy and 14 HC
| Influenza | 2b | All patients on anti-TNFα were seroprotected, but they had a smaller increase in GMT after vaccination. | – |
Aikawa et al. [36]a
| 16 anti-TNFα 63 DMARD/IS (prednisone, leflunomide, CYC, SSZ) 47 MTX 5–50 mg/week
Versus 91 HC
| Influenza | IG: 2b DAS: 3 | Seroconverted patients (83.2 %) and non-seroconverted patients (16.8 %) had similar types and doses of therapy. | – |
Carvalho et al. [23] | 31 MTX or leflunomide 6 GC dose 0.05–1 mg/kg/day 5 anti-TNFα 1 CSP
Versus 10 HC
| Influenza | 3 | Anti-TNFα users had lower seroconversion and seroprotection rates to the H1N1 strain (60 versus 100 % in HC). 80 % of patients were seroprotected against the H2N3 and B strains, compared to 80 % and 100 % of HC, respectively. | – |
Moses et.al. [21] | 78 anti-TNFα mean dose 6.9 ± 1.8 mg/kg 53 AZA 36 MTX 14 6-MP | HBV | 3 | 56 % of the 87 patients were still seroprotected after HBV vaccination in the past, and 76 % of the 34 patients who received the booster vaccine were seroprotected 1 month after administration. | – |
Heijstek et al. [15] | 37 NSAIDs 24 MTX mean dose 10.2 mg/m2/week 9 anti-TNFα median dose 45 mg/week 6 other DMARDs 1 anti IL-1R
Versus 55 HC
| bHPV | 3 | All patients using anti-TNFα were seropositive after 3 vaccines, with lower GMTs. | – |
Stoof et al. [22] | 108 MTX 60 biologicals 14 GC
Versus 1527 HC
| MenC | 3 | Use of biologicals accelerated the decline of antibody levels over time. | – |
Heijstek et al. [14••] | Vaccinated: 38 NSAIDs 29 MTX mean dose 10.6 mg/m2/week 6 anti-TNFα median dose 15 mg/week 3 anti IL-1R median dose 1.6 mg/kg 2 oral GC 1 leflunomide Unvaccinated: 36 NSAIDs 31 MTX mean dose 11.6 mg/m2/week 4 anti-TNFα median dose 21 mg/week 2 anti IL-1R median dose 1.4 mg/kg 1 oral GC 1 leflunomide | MMR | 3 | All patients using biologicals were seroprotected against measles, rubella and mumps. | No MMR infections induced by vaccine in patients on DMARDs or in patients on biologicals. |
Shinoki et al. [42] | 27 anti-IL6 24 GC (mean dose 7.3 mg/day)
Versus 17 HC
| Influenza | 3 | Seroconversion, seroprotection and GMTs similar in patients using anti-IL6 and healthy controls | – |
Methotrexate
Biologicals
Immunogenicity of Non-live Composite Vaccines
Human Papillomavirus Vaccine
Vaccine | Patients | Medication | LoE | Immunogenicity | Safety |
---|---|---|---|---|---|
Live-attenuated | |||||
Bacillus Calmette-Guérin | |||||
Hsu et al. [44] | 281 KD | Unknown | 3 | – | Local inflammation at BCG vaccination site in up to 50 % of KD patients. |
Kuniyuki et al. [45] | 1 KD | Unknown | 4 | – | Case report of local inflammation at BCG vaccination site. |
Antony et al. [46] | 2 KD | Unknown | 4 | – | Case report of local inflammation at BCG vaccination site. |
Weinstein [47] | 1 KD | Unknown | 4 | – | Case report of local inflammation at BCG vaccination site. |
Chalmers et al. [48] | 1 KD | Unknown | 4 | – | Case report of local inflammation at BCG vaccination site. |
Kiray et al. [27] | 115 JIA 45 HC | 55 GC 73 MTX 17 sulphasalazine | 2B | PPD reactivity several years after 1–2 BCG vaccinations: induration size smaller in JIA patients, 39 % JIA versus 84 % HC reacted to PPD. No influence of IS drugs. | – |
Uehara et al. [49] | 15,524 KD | Unknown | 3 | – | Local inflammation at BCG vaccination site in 50 % of KD patients. |
Measles, mumps, rubella | |||||
Drachtman et al. [50] | 1 ITP | None | 4 | – | Case report of a flare of ITP 7 weeks after MMR booster. |
Heijstek et al. [27] | 207 JIA | 49 MTX | 2B | – | No increase in disease activity. |
Borte et al. [34] | 15 JIA 22 HC | 5 MTX 4 years post MMR 5 MTX 5 MTX + anti-TNFα | 2B | No interference of MTX or anti-TNFα with cellular or humoral immunity. | No increase in disease activity or medication use after MMR booster. No influence of MTX or anti-TNFα. |
Korematsu et al. [51] | 1 JIA | NSAIDS | 4 | – | Case report of a flare of systemic JIA 5 days after rubella vaccination. |
Miyamoto et al. [20] | 30 JSLE 14 HC | 25 HCQ 19 oral GC 14 AZA 9 IV GC 2 CFMpulse 2 CY 2 MTX 1 MMF | 2B | At 7–16 years after vaccination, protective antibody levels against measles were similar in patients and controls. | – |
Heijstek et al. [18] | 400 JIA 2176 HC | 246 NSAID 93 MTX 28 oral GC (median dose 10 mg/day) 24 DMARD 8 anti-TNFα | 2C | Protective antibody levels against mumps and rubella in patients were lower after past vaccination (time since vaccination up to 10 years; adjusted OR for seroprotection between 0.1 and 0.4). Protective antibody levels against measles did not significantly differ from controls. | - |
Heijstek et al. [14••] | 68 JIA patients (vaccinated) 69 JIA patients, (unvaccinated) | Vaccinated: 38 NSAIDs 29 MTX 6 anti-TNFα 3 anti-IL1-R 2 oral GC 1 leflunomide Unvaccinated: 36 NSAIDs 31 MTX 4 anti-TNFα 2 anti-IL1-R 1 oral GC 1 leflunomide | 1B | All vaccinated patients had protective antibody levels against MMR, with a significant increase in GMC. Two patients became seronegative over time. | No MMR infections induced by vaccine. Frequency of flares was similar in vaccinated and unvaccinated patients. Patients on biologics did not show any MMR infections, flares or increase in disease activity. |
Varicella zoster virus | |||||
Pileggi et al. [17] | 17 JIA 4 JDM 4 other ARD 18 HC | 13 GC 4.2 mg/day 25 MTX 5 DMARD | 2B | Seroprotection 50 % in patients versus 72 % in HC (within range of historical healthy cohort). 2 of 8 patients that were exposed to VZV developed chickenpox, 1 of these patients was on anti-TNFα. | 3 patients with mild self-limiting VZV-like rash. No increase in disease activity. |
Lu et al. [38] | 6 IBD | 6 6-MP 2 anti-TNFα | 4 | Seroprotection in 5/6 patients shortly after VZV vaccination. | No serious adverse events after primary/booster VZV vaccination, despite anti-TNFα usage. |
Barbosa et al. [13••] | 28 JSLE patients (vaccinated) 26 JSLE patients (unvaccinated) 28 HC | Vaccinated: 27 HCQ 18 GC (mean dose 7.5 ± 3.9 mg) 9 AZA 2 MTX Unvaccinated: 22 HCQ 18 GC (mean dose 9.4 ± 4.8) 12 AZA 2 CFM | 1B | Patients showed a similar increase in GMT as healthy controls.
NB: seroprotection 100 % in patients and controls before vaccination. | Frequency of flares was similar in vaccinated and unvaccinated patients. |
Non-live composite | |||||
Human papilloma virus | |||||
Soybilgic et al. [52] | 27 JSLE | 27 HCQ 16 GC (mean dose 12.6 mg) 9 AZA 9 MMF 6 MTX | 3 | All but one patient seroconverted for all 4 HPV types. | No increase in disease activity after vaccination. |
Heijstek et.al. [16] | 6 JSLE 6 JDM 49 HC | 6 GC 2 HCQ 2 MTX 1 AZA 1 MMF | 2b | All but one JDM patient and all controls seroconverted after the third dose. The GMT in patients was lower than in HC. | No increase in disease activity after vaccination. |
Heijstek et al. [15] | 68 JIA 55 HC | 37 NSAIDs 24 MTX 9 anti-TNFα 6 other DMARDs 1 anti-IL-1R | 2b | All participants were seropositive after vaccination. The GMT in patients was lower than in HC. | No disease flares, no increase in disease activity after vaccination. |
Hepatitis A virus | |||||
Beran et al. [53] | 10 AIH | Unknown | 3 | 100 % response rate. | No severe adverse events. No increase in disease activity. |
Erguven et al. [40] | 47 JIA 67 HC | 12 GC 29 MTX 11 GC + MTX 19 sulphasalazine 4 anti-TNFα | 2B | 4 patients on anti-TNFα (systemic JIA) negative for anti-HAV antibodies after vaccination. 100 % response rate in all other patients and HC. | No adverse events. No increase in disease activity. |
Moses et al. [54] | 12 pIBD | 12 anti-TNFα 2 MTX | 3 | Seroconversion rate was 92 %. | – |
Hepatitis B virus (DNA) | |||||
Kasapçopur et al. [26] | 39 JIA 41 HC | 20 GC 22 MTX | 2B | Seroprotection in 38/39 patients vaccination, comparable to HC. No effect IS drugs. | No increase in disease activity. |
Beran et al. [53] | 10 AIH | Unknown | 3 | 100 % response rate in patients <15 years. 50 % response rate in 4 patients aged 16–20 year, 1 used GCs 5 mg/day. | No severe adverse events. No increase in disease activity. |
Aytac et al. [30] | 20 JSLE 24 HC | 17 GC (mean dose 6.25 mg/day) 11 AZA 3 MMF 2 HCQ 3 no medication | 2B | Seroconversion and seroprotection lower in patients than in controls (80 versus 100 %). The GMT in patients was lower than in HC. | No increase in disease activity after vaccination. |
Moses et al. [21] | 87 pIBD, of whom 34 received booster vaccine | 87 anti-TNFα (mean 6.9 ± 1.8 mg/kg/dose) 53 AZA 36 MTX 14 6-MP | 3 | 56 % of patients were protected after HBV vaccination in the past; 76 % of 34 patients had an adequate response to the booster vaccine. | – |
Maritsi et al. [19] | 89 newly diagnosed JIA 89 HC | None: study measured protective antibody levels from NVP | 2B | After a median time after vaccination of 5 years, the level of protective anti-HBs-antibody levels was significantly lower in JIA patients (55 %) than in HC (92 %). | – |
Seasonal influenza | |||||
Denman et al. [55] | 3 JIA 20 HC | 3 chlorambucil | 2B | Similar anti-influenza antibody concentrations. No effect of IS drugs. | – |
Malleson et al. [43] | 34 JIA 13 HC | 7 GC 9 DMARD | 2B | Similar anti-influenza antibody concentrations and seroconversion rate as HC. No effect of IS drugs. | Similar adverse events as healthy controls. 4 flares per 145 patient months before versus 3 flares per 34 patient months after vaccination. As a group, more patients improved than deteriorated. |
Kanakoudi-Tsakalidou et al. [25] | 49 JIA 11 SLE 3 JDM 7 other ARD 5 HC | 16 GC 16 GC + MTX 11 GC + CY 6 GC + AZA 8 GC + MTX + CY 5 MTX 4 CY 4 MTX + CY | 2B | 15 non-responders among patients. Similar immunogenicity between patients. | No severe adverse events. No increase in disease activity. |
Mamula et al. [56] | 51 IBD 29 HC | 12 GC 1 MTX 18 6-MP 10 6-MP + anti-TNFα 6 MTX + anti-TNFα | 2B | In general, lower responses to 1 strain compared with HC. Lower responses in patients on anti-TNFα + DMARDs towards 2 strains. | Similar non-severe adverse events as HC. No increase in disease activity. |
Lu et al. [28] | 146 IBD | 12 GC 59 MTX/AZA/6-MP 45 anti-TNFα 10 tacrolimus | 3 | In general good immunogenicity. Patients on anti-TNFα lower responses to 1 strain in contrast to other IS drugs. | No severe adverse events. No increase in disease activity. |
Ogimi et al. [29] | 23 JIA 12 SLE 6 JDM 2 KD 2 MCTD 4 other ARD 36 HC | 14 GC 7 GC + MTX 7 GC + MMF 4 GC + other DMARD 13 GC + 2 DMARD 2 CY 1 MTX 1 MTX + CFM + AZA | 2B | Similar anti-influenza antibody concentrations and seroconversion rate as HC. No effect of IS drugs. Of note, pre-vaccination anti-influenza antibody concentrations were higher in patients. | Similar non-severe adverse events as HC. 2 patients (1 JIA, 1 Takayasu arteritis) experienced a flare of disease within 2 weeks after vaccination. |
Woerner et al. [35] | 25 JIA 3 uveitis 2 IBD 2 RMO 1 vasculitis 1 JSLE 1 MCTD 16 HC | 18 MTX 10 anti-TNFα 8 MTX + anti-TNFα | 2B | Seroprotection and seroconversion were similar in patients and controls. The GMT in patients was lower than in HC. | – |
Dell’Era et al. [41] | 60 JIA 30 HC | 30 DMARD (unspecified) 32 MTX 30 anti-TNFα | 2B | Seroprotection and seroconversion were similar in patients treated with DMARDs and controls. | No increase in disease activity after vaccination. |
Shimizu et al. [57] | 1 soJIA | 1 anti-IL6 | 3 | – | Case report of disease flare after influenza vaccination. |
Shinoki et al. [42] | 27 soJIA 17 HC | 27 anti-IL6 24 GC (mean dose 7.3 mg/day) | 2B | Seroconversion, seroconversion and GMT were similar to healthy controls. | No increase in disease activity after vaccination. |
Toplak et al. [24] | 31 JIA (vaccinated) 31 JIA (unvaccinated) 17 HC | 18 without therapy 7 DMARD + GC (<10 mg/day) 4 anti-TNFα 3 leflunomide 2 sulphasalazine | 2B | Seroprotection similar to controls after 1 month, similar decline in protective antibodies after 6 months. | Flare rate in vaccinated group 36 %, in unvaccinated group 23 %, but the unvaccinated group had less active disease and selection of control group unclear. |
Aikawa et al. [31]a
| 99 JSLE 93 JIA 18 JDM 11 JScl 16 vasculitis 91 HC | 54 GC <20 mg/day 36 GC ≥20 mg/day 74 MTX 43 AZA 23 CY 13 MMF 6 leflunomide 3 CFM | 2B | Compared to HC, seroconversion, seroprotection and GMT were significantly lower in JSLE patients and lower in other pedRD. | – |
Guissa et al. [58]a
| 30 JDM 81 HC | 12 GC <20 mg/day 3 GC ≥20 mg/day 14 MTX 7 HCQ 6 CY 2 AZA | 2B | Similar seroprotection rate in patients and controls.
NB: 12 of these patients are also included in study of Aikawa et al. 2012. | No disease flares, no increase in disease activity after vaccination. |
Aikawa et al. [36]a
| 95 JIA 91 HC | 63 DMARD/IS (prednisone, leflunomide, CFM sulphasalazine) 47 MTX 16 anti-TNFα | 2B | Significantly lower seroconversion in patients, similar seroprotection and GMT in patients and controls.
NB: patients in this study are also included in study of Aikawa et al. 2012. | No disease flares, no increase in disease activity after vaccination. |
Campos et al. [32] | 110 JSLE 102 HC | 92 antimalarials 43 GC <20 mg/day 40 GC ≥20 mg/day 44 AZA 15 MMF 14 MTX 3 CFM 2 CY | 2B | Seroconversion, seroprotection and GMT were significantly lower in patients than in controls. A SLEDAI >8 was associated with non-response in multivariate analysis. | No increase in disease activity after vaccination. |
Carvalho et al. [23] | 44 JIA 10 HC | 31 MTX or leflunomide 6 GC (mean dose 0.3 mg/kg/day) 5 anti-TNFα 1 CY | 2B | Seroprotection in patients similar to controls. | No increase in disease activity after vaccination. |
Meningococcal (MenC) | |||||
Zonneveld-Huijssoon et al. [59] | 234 JIA | 36 MTX <10 mg/m2/week 15 MTX >10 mg/m2/week 7 sulphasalazine 8 anti-TNFα 1 CFM 2 MTX + sulphasalazine | 2B | In general, good protection in all JIA patients. Lower MenC-specific antibody responses in patients receiving IS drugs, but sufficient bactericidal activity as patients with high responses towards the MenC vaccination. | No increase in disease activity, no increased risk of a relapse after vaccination. |
Stoof et al. [22] | 127 JIA 1527 HC | 108 MTX 60 biologicals 14 GC | 2C | Highest post-vaccination antibody concentrations were seen in the eldest patients at time of vaccination. Antibody levels waned over time in all patients. The persistence over time was similar to healthy controls. | – |
Pneumococcal (PCV7) | |||||
Farmaki et al. [39] | 63 JIA | 32 DMARD ± C 31 DMARD + anti-TNFα ± GC | 2B | Lower antibody concentrations against 3/7 serotypes, but similar response and protection rate. No pneumococcal disease or respiratory tract symptoms during 2-year follow-up | No increase in disease activity. Similar mild adverse events in patients with and without anti-TNFα. |
Tetanus-diphtheria | |||||
Denman et al. (TT vaccine) [55] | 3 JIA 20 HC | 3 chlorambucil | 2B | Similar anti-TT antibody concentrations. No effect of IS drugs. | – |
Höyeraal et al. [60] | 34 JIA 34 HC | Unknown | 3 | Higher antibody humoral responses to TT and diphtheria, although not corrected for higher baseline antibody levels. | – |
Kashef et al. (TT vaccine) [61] | 40 SLE 60 HC | 10 GC + CFM 13 GC + AZA 5 GC + CFM + AZA 8 GC + MMF | 3 | Several years after vaccination, similar seroprotection rate (100 %) against TT. Influence IS drug unknown. | – |
Miyamoto et al. (TT vaccine) [20] | 30 JSLE 14 HC | 25 HCQ 19 oral GC 14 AZA 9 I.V. GC 2 CFMpulse 2 CY 2 MTX 1 MMF | 2B | Patients had protective antibody levels of tetanus antibodies than controls. No effect of IS drugs. | – |
Heijstek et al. (TD vaccine) [18] | 400 JIA 2176 HC | 246 NSAID 93 MTX 28 oral GC (median dose 10 mg/day) 24 DMARD 8 anti-TNFα | 2C | Protective antibody levels against diphtheria and tetanus in patients were lower after past vaccination (time since vaccination up to 10 years; adjusted OR for seroprotection between 0.1 and 0.4). |