Table 3.
Studies of LAVs in a pediatric population on immunosuppressive therapy
| Year | Authors | Study design | Vaccine (n) | n | Age (range) | Disease | Biologics (n) | Safety | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| 2020 | Uziel et al. [53] | Retrospective study. 13 pediatric rheumatology centers in 10 countries | MMR-V booster | 234 | 5 ± 2.7 y |
211 JIA 11 JDM 5 Scle 5 isolated IU 1 NOMID 1 MKD 1 FMF |
MTX m (124) MTX + biologics (62): INX (1) ETN (33) ADA (22) TCZ (1) CAM (5) MTX + DMARDs (9): CsA (7) Salazopirin (1) LEF (1) Biologics (39): INX (1) ETN (16) ADA (6) TCZ (4) ANK (6) CAM (6) |
No vaccine-related infection of measles, rubella, mumps, or varicella was reported. Mild adverse effects were reported |
MMR-V booster vaccines were safe |
| 2018 | Jeyaratnam et al. [56] | Multicenter survey (85 physicians from 23 countries) |
1st dose: YF (4); MMR-V (1); Var (1) Booster: MMR (7); Var (3); oral polio (1) |
17 | 9 (1–58 y) |
7 JIA 5 CAPS 4 MKD 1 FMF |
Anti-IL-1 (10) Anti-IL-6 (7) |
SAE: 2 pts (needing hospitalization) | Study reflects the reluctance of physicians to administer LAVs to patients using biologicals. LAVs cannot be considered entirely safe in patients using IL-1 or IL-6 blockade |
| 2018 | Speth et al. [57] | Prospective study |
Var 1st dose (6): 3 LIIS 3 HIIS 1st + 2nd dose (9): 4 LIIS (6 wks apart) 5 HIIS (3 mo apart) Booster (9): 2 LIIS 7 HIIS |
23 |
LIIS: 8.3 (1.8-17.8 y) HIIS: 9.7 (2.7-17.8 y) |
LIIS: 8 JIA 1 SS HIIS: 11 JIA 2 JDM 1 MPA |
MTX m (1); MMF m (1); LEF m (1); ETN m (3) LEF + biologics: + ABA (1) + ANK + Cs (1) + ETN + Cs (1) + TCZ (1) MTX + biologics: ADA (1) ANK + Cs (1) TCZ (1) |
No vaccine-induced varicella disease symptoms. No other AEs within 4 wk after vaccination |
Var vaccination is safe in children 5 out of the 6 pts naïve to Var vaccination had only one dose due to an increase in Var-IgG-level |
| 2017 | Groot et al. [58] | Prospective study | Var (1st and 2nd doses) | 67 |
G1: 28 pts—5 (2–15 y) received 1 dose 21 pts—3.5 (2–17 y) received 2 doses CG: 8.5 (3–18 y) received one dose |
G1: 39 JIA 5 JDM 5 JScle CG: 18 HP |
MTX m (25) MTX + Cs (18) Biologics (3): ADA—received only the 1st dose Received 2 doses: ETN—responded to 2nd dose ABA—unresponsive |
Pt on ABA developed chicken pox | Biologics affected the immunogenicity of the vaccine in contrast to immunosuppressive drugs |
| 2015 | Toplak and Avcin [59] | Prospective study | Var (1st and 2nd doses) | 6 | 4.7 (2.5–7 y) | JIA |
ETN (3) INX (1) TCZ (2) |
SAE: 0 Mild Var infection (4 mo after the 2nd dose)—1 Pt [81] with low protective levels of Ab |
Variable humoral response to vaccination, which did not always provide adequate protection 5 pts (83%) had protective Ab levels 6 wk after the 2nd dose |
| 2013 | Heijstek et al. [55] | RCT | MMR booster | 131 |
Vg: 6.3 (5.9–6.7 y) CG: 6.5 (6.2–6.9 y) |
Vg: 63 CG: 68 (no vaccination) |
ETN (5) ADA (1)* ANK (3) 2 pts took oral Cs concomitantly |
SAE: 0 None showed disease caused by attenuated viruses |
Biologics did not affect humoral responses when stopped 5 half-lives before administration MMR booster induced high seroprotection rates in all pts At 12 mo after vaccination, Ab concentrations were significantly higher |
| 2009 | Borte et al. [54] | Prospective study | MMR booster | 15 | 6–17 y |
15 JIA: G1: 5 G2a: 5 G2b: 5 CG: 20 HP |
G2b: low-dose MTX in combination with anti-TNF |
No mumps, measles, and rubella infections were seen 6 mo after the booster | MMR booster was effective as virus specific IgG levels were not affected |
Ab antibody, ABA abatacept, ADA adalimumab, AE adverse event, ANK anakinra, CAM canakinumab, CAPS cryopyrin-associated periodic syndrome, CG control group, Cs corticosteroids, CsA cyclosporine, DMARDs disease modifying antirheumatic drugs, ETN etanercept, FMF familial Mediterranean fever, G group, HIIS high-intensity immunosuppression including biological therapy, HP healthy persons, Ig immunoglobulin, IL interleukin, INX infliximab, IU idiopathic uveitis, JDM juvenile dermatomyositis, JIA juvenile idiopathic arthritis, JScle juvenile scleroderma, LAVs live attenuated vaccines, LEF leflunomide, LIIS low-intensity immunosuppression including biological therapy, m monotherapy, MKD mevalonate kinase deficiency, MMF mycophenolate mofetil, MMR measles, mumps, and rubella, MMR-V measles, mumps, rubella, and varicella, mo months, MPA microscopic polyangiitis, MTX methotrexate, NOMID neonatal onset multi-inflammatory disease, pt(s) patient(s), RCT randomized controlled trial, SAE serious adverse event, Scle scleroderma, SS Sjögren syndrome, TCZ tocilizumab, Var varicella, Vg vaccinated group, wk weeks, y years, YF yellow fever.
*Were stopped before vaccination at 5 times their half-lives