The safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade: an international survey

Abstract

BackgroundWithholding live-attenuated vaccines in patients using interleukin (IL)-1 or IL-6 blocking agents is recommended by guidelines for both pediatric and adult rheumatic diseases, since there is a risk of infection in an immune suppressed host. However, this has never been studied. This retrospective, multicenter survey aimed to evaluate the safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade.MethodsWe contacted physicians involved in the treatment of autoinflammatory diseases to investigate potential cases. Patients were included if a live-attenuated vaccine had been administered while they were on IL-1 or IL-6 blockade.ResultsSeventeen patients were included in this survey (7 systemic juvenile idiopathic arthritis (sJIA), 5 cryopyrin associated periodic syndrome (CAPS), 4 mevalonate kinase deficiency (MKD) and 1 familial Mediterranean fever (FMF). Three patients experienced an adverse event, of which two were serious adverse events (a varicella zoster infection after varicella zoster booster vaccination, and a pneumonia after MMR booster). One additional patient had diarrhea after oral polio vaccine. Further, seven patients experienced a flare of their disease, which were generally mild. Eight patients did not experience an adverse event or a flare.ConclusionWe have described a case series of seventeen patients who received a live-attenuated vaccine while using IL-1 or IL-6 blocking medication. The findings of this survey are not a reason to adapt the existing guidelines. Prospective trials are needed in order to acquire more evidence about the safety and efficacy before considering adaptation of guidelines.

A practical approach for vaccinations including COVID-19 in autoimmune/autoinflammatory rheumatic diseases: a non-systematic review

“…As a general rule, live-attenuated vaccines are not recommended for both pediatric and adult patients using IL-1 blocking agents [67][68][69]. A recent retrospective, multicenter survey evaluated the safety and efficacy of live-attenuated vaccines in patients using IL-1 or IL-6 blocking agents [70] and reported disease activation in some patients after vaccination. Discontinuation of IL-1 blockers before vaccination was seemingly the cause, and the authors concluded that the current data is inadequate to draw any conclusions about the safety of these vaccines in patients using IL-1 and physicians should balance the risk of infections versus the risk of disease flares and adverse events for each patient.…”

Recommendations for Vaccination in Children with Atopic Dermatitis Treated with Dupilumab: A Consensus Meeting, 2020

“…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.…”

Human Autoinflammatory Diseases Mediated by NLRP3-, Pyrin-, NLRP1-, and NLRC4-Inflammasome Dysregulation Updates on Diagnosis, Treatment, and the Respective Roles of IL-1 and IL-18

“…The administration of canakinumab to healthy subjects 2 weeks prior to influenza and meningococcal vaccinations demonstrated that similar protective antibody titers developed in subjects receiving canakinumab and those who did not ( 63 ). Vaccination of 17 CAPS patients with polysaccharide or conjugate pneumococcal vaccines, led to disease flares in 12 patients, who all received polysaccharide vaccines ( 64 ) and a retrospective survey in 17 patients (5 CAPS, 4 MKD, 1 FMF, 7 sJIA) on IL-1 or IL-6 blockade who received live vaccines (varicella, MMR, oral polio, and yellow fever), recorded disease flares when IL-1 blocking treatment was held for vaccination and possible vaccine-induced infections (one of 5 developed varicella zoster, one of 8 post-MMR pneumonia and 1 of 1 diarrhea post-oral polio vaccination) ( 65 ). In the absence of larger studies providers need to balance the risks and benefits.…”