Shingrix in Patients With Rheumatic Diseases: a Double-blind Placebo-controlled RCT

A double-blind randomized controlled trial on the safety and immunogenicity of the recombinant subunit herpes zoster vaccine, Shingrix, in patients with rheumatic diseases undergoing immunosuppressive or biologic/targeted DMARD therapies.

Duration of study: 60 weeks

• recombinant subunit herpes zoster vaccine (Biological), also known as Shingrix: vaccine administration

Primary outcomes

• humoral immune response to Shingrix [week 12 (compared with baseline)]: proportion of patients with 4x fold increase in anti-gE antibody titer

Secondary outcomes

• Humoral immune response [week 52]: proportion of patients with 4x fold increase in anti-gE antibody titer
• adverse events [7 days after injection]: solicited
• adverse events [4 weeks after injection]: unsolicited
• flares of underlying diseases [week 26 and 60]: disease flares
• herpes zoster infection [week 60]: herpes zoster infection
• cell mediated response to vaccine [week 12 from baseline]: in 40 patients (20 from each arm); number of IFNγ-secreting CD4+ T cell colonies on ELISPOT assay

Sex: All, ages: 18 Years to any

Inclusion criteria for patients:

1. Patients with a diagnosis of rheumatic or immune-mediated diseases eg. SLE, RA, PSA, SpA, inflammatory myopathies, ANCA-related and large vessel vasculitides
2. Age ≥18 years
3. Stable or reducing doses of any the following immunosuppressive regimens within 4 weeks of study entry:

   1. Prednisolone ≥20mg/kg/day ± mycophenolate mofetil, azathioprine or the calcineurin inhibitors
   2. Cyclophosphamide (intravenous pulses or daily oral)
   3. B-cell depleting biological agents and their biosimilars eg. belimumab, anti-CD20 agents (next scheduled dose should be arranged to at least 12 weeks after study entry for rituximab or obinutuzumab)
   4. Anti-TNFα biological agents and their biosimilars eg. infliximab, etanercept, adalimumab, golimumab, certolizumab
   5. Anti-interleukin-6 biological agents eg. tocilizumab, sarilumab
   6. Other biological agents eg. abatacept, ustekinumab, secukinumab, ixekizumab
   7. The JAK inhibitors eg. tofacitinib, baricitinib, upadacitinib
4. Female patients with reproductive potential are allowed to participate in this study provided that they are willing to practice contraception for until at least 12 months after vaccination
5. Willing to comply with all study procedures

Exclusion criteria for patients:

1. Active infection, including upper respiratory tract infection
2. Active HZ infection
3. Active untreated tuberculosis
4. HIV infection
5. History of HZ or varicella vaccination in the past
6. History of allergy to any vaccines
7. Patients who are pregnant or plan to become pregnancy within one year of study entry
8. Lactating women
9. Patients who cannot give a written consent (mentally incapable or illiterate)

• Chi Chiu Mok, Principal investigator, Tuen Mun Hospital