Table 3.
Overview of real-world evidence investigating the incidence of adverse events and disease flares after administration of the recombinant zoster vaccine in patients with immune-mediated diseases.
| Publication | Study type/period | Follow-up | Population | Sample size | Principal underlying conditions, n (%) | Concomitant medication, n (%) | Flare incidencea | AE incidencea,b |
|---|---|---|---|---|---|---|---|---|
| Gupta et al. J Clin Rheumatol 202245 | Medical records review Jan 2018–Mar 2020 |
3 months | Adults with rheumatic disease | RZV – one dose: 31 RZV – two doses: 34 |
RA, 20 (31) Polymyalgia rheumatica, 11 (17) Sjögren syndrome, 6 (9) SLE, 5 (8) PsA, 5 (8) Scleroderma, 4 (6) IBD arthropathy, 3 (5) AS, 2 (3) Other, 8 (15) |
Biologic DMARD, 16 (24.6) Nonbiologic DMARD, 29 (44.6) No DMARD, 20 (30.8) |
Baseline period: n = 8 (12.3%) After RZV: n = 3 (9.2%) |
Minor, systemic AEs: n = 4 (6.2%) |
| Venerito et al. Int J Mol Sci 202349 | Prospective study at the RA clinic of a tertiary center Feb−Jun 2022 |
3 months | Patients with RA on JAK inhibitors or biologic DMARD who received two doses of RZV | JAK inhibitors: n = 26 Biologic DMARD: n = 26 | RA, 52 (100) | JAK inhibitors, 26 (50) Biologic DMARD, 26 (50) |
After RZV: n = 0 | Local site reactions n = 45 (86.5%) Most frequent systemic AEs: fatigue (n = 13, 25%); fever (n = 11, 21.2%); headache (n = 11, 21.2%) No serious AEs |
| Khan et al. J Crohns Colitis 202242 | Retrospective cohort study using Veterans Affairs Healthcare System data Study period NR |
90 days | Patients with IBD | RZV – 1677 Unvaccinated matched controls –1677 |
IBD, 1677 (100) | Mesalamine, 1450 (86) Anti-TNF agents, 109 (7) Thiopurines, 105 (6) Anti-TNF and thiopurines, 6 (<1) Vedolizumab, 7 (<1) |
Cumulative 90-day incidence of IBD flare: 1.2% (vaccinated) vs. 1.0% (unvaccinated); p = 0.503 | NR |
| Lenfant et al.Rheumatology (Oxford) 202143 | Single-center review of electronic medical records Feb 2018–Mar 2020 |
Median 36 weeks | Adults with (n = 359) or without (n = 263) IMID | RZV – one dose: 146 RZV – two doses: 476 | RA, 88 (25)c Vasculitis, 50 (14)c PMR, 29 (8)c Gout, 28 (8)c SLE, 24 (7)c |
Non-biologic DMARD, 176 (49) Glucocorticoids, 125 (35) Biologic DMARD, 68 (19) Other biologics, 47 (13) |
In the IMID subgroupd
n = 59/359 (16.4%): RA, 21/88 (24%) Vasculitis, 5/50 (10%) PMR, 5/29 (17%) Gout, 5/28 (18%) SLE, 4/24 (17%) |
In the entire population, n = 54 (8.7%): most frequently, injection-site reactions (n = 19, 3%); general fatigue (n = 12, 2%); myalgia (n = 12; 2%); and fever (n = 6; 1%) |
| Leung et al.Arthritis Rheumatol 202241e | SCCS analysis of medical claims data from the IBM MarketScan (patients aged 50–64 years; 2017–2019) and Centers for Medicare and Medicaid Services Medicare (patients aged ≥ 65 years; 2017–2020) databases | ≥ 6 months | Aged ≥ 50 years, with IMID | At least one RZV dose: MarketScan, n = 7207; Medicare, n = 72,468 | Marketscan: RA, 3415 (47.4) PsO, 1039 (14.4) PsA, 992 (13.8) IBD, 1477 (20.5) UC, 916 (12.7) CD, 594 (8.2) SLE, 507 (7.0) AxSpA, 216 (3.0) AS, 166 (2.3) Medicaid: RA, 45,851 (63.3) IBD, 12,679 (17.5) UC, 7416 (10.2) PsA, 6678 (9.2) PsO, 5993 (8.3) CD, 5384 (7.4) SLE, 4205 (5.8) AxSpA, 86 (<1) AS, 72 (<1) |
NR | At least one RZV dose: risk window – MarketScan 9%, Medicare 11–12%; control window –MarketScan 10%, Medicare 13%f | NR |
| Raza et al. South Med J 202244 | Single-center, retrospective study 2018 |
4.78 months after second vaccine | Patients with rheumatic disease who received two doses of RZV | N = 47 | RA, 36 (76.6) SLE, 5 (10.6) Fibromyalgia, 3 (6.4) Vasculitis, 2 (4.2) Sjögren syndrome, 2 (4.2) |
Conventional DMARD, 28 (59) Biologic/targeted DMARD, 23 (49) Both conventional and biologic/targeted DMARD, 12 (25) |
Four events of disease flare occurred at subsequent post-vaccination follow-up visits | Mild AEs: 6.4% |
| Satyam et al. Dig Dis Sci 202039 | Prospective, observational study at tertiary IBD referral center Feb 2018–Jul 2019 |
Median (IQR) 207 days (169–304.5) days | Patients with IBD | At least one RZV dose: n = 67 | UC, n = 28 CD, n = 39 | Prednisone, 7 (10.4) Immunomodulator (6-mercaptopurine, azathioprine, or methotrexate), 11 (16.4) Anti-TNF inhibitor, 9 (13.4) Vedolizumab, 15 (22.4) Ustekinumab, 9 (13.4) Tofacitinib, 3 (4.5) |
1/67 (1.5%) | Local AEs: 74.6% Systemic AEs: 56.7% |
| Stevens et al. ACR Open Rheumatol 202040 | Retrospective chart review at a rheumatology outpatient center Feb 2018–Feb 2019 |
Mean (range): 13.2 (1.0–50.0) weeks | Patients with RA or other SRD | At least one RZV dose: n = 403 | RA, n = 239 (59.3) SRD, n = 164 (40.7) PsA, n = 28 (6.9) SLE, n = 16 (3.9) Spondylitis, n = 12 (2.9) Sjögren syndrome, n = 12 (2.9) Giant cell arteritis, n = 8 (1.9) Other, n = 88 (21.8) |
Any immunosuppressant, n = 316 (78.4) MTX, n = 143 (35.5) Prednisone, n = 106 (26.3) Tofacitinib, n = 52 (12.9) TNF inhibitor, n = 105 (26.1) Other biologic, n = 49 (12.2) Other immunosuppressant, n = 49 (12.2) |
After first RZV dose: 23 (5.7%) After second RZV dose: 5 (2.3%) After both RZV doses: 1 (0.2%) |
Mild AEs: n = 51 (12.7%) After first RZV dose: 43 (10.7%) After second RZV dose: 12 (5.4%) After both RZV doses: n = 4 (<1%) |
aUnless otherwise stated, n = number of patients.
bAfter RZV.
cUnderlying conditions in the IMID subgroup.
dMultivariable analysis revealed that glucocorticoid use at the time of RZV dosing was the only factor significantly associated with flares (odds ratio 2.31; 95% CI: 1.30–4.10; p = .004).
eFlare rate for each IMID can be found in Leung et al. Arthritis Rheumatol 2022.41
fFor specific values for flare incidence according to IMID, the reader is referred to the original Leung et al. paper.41
AE, adverse event; AS, ankylosing spondylitis; axSpA, axial spondyloarthritis; CD, Crohn’s disease; DMARD, disease-modifying antirheumatic drug; IBD, inflammatory bowel disease; IMID, immune-mediated inflammatory disease; JAK, Janus kinase; MTX, methotrexate; NR, not recorded; PMR, polymyalgia rheumatica; PsA, psoriatic arthritis; pts, patients; PsO, psoriasis; RA, rheumatoid arthritis; RZV, recombinant zoster vaccine; SCCS, self-controlled case series; SLE, systemic lupus erythematosus; SRD, systemic rheumatic disease; TNF, tumor necrosis factor; UC, ulcerative colitis.