AB1596 REAL-LIFE STUDY OF IMMUNOGENECITY AND SAFETY OF THE RECOMBINANT VACCINE AGAINST VARICELLA ZOSTER VIRUS IN PATIENTS WITH RHEUMATIC DISEASES TREATED WITH JANUS KINASE INHIBITORS

Abstract

BackgroundAdjuvanted recombinant varicella zoster virus subunit vaccine (ARZVV) has been recently approved for preventing reactivation of latent varicella zoster virus in selected groups of patients. Patients with chronic inflammatory diseases are at major risk of this reactivation, developing herpes zoster (HZ) infection (shingles). This risk is further increased under immunosuppressive treatment with janus kinase inhibitors (JAKi). ARZVV is available in Spain since March 2021 for patients treated with JAKi, among other indications. At the present, no real-life post commercialization studies have been published in patients with rheumatic diseases and JAKi vaccinated with ARZVV.ObjectivesTo assess humoral immunogenicity and safety of ARZVV in patients with rheumatic diseases treated with JAKi.MethodsImmunogenicity and short-term safety were evaluated in a cohort of patients treated with Janus Kinase inhibitors in a descriptive prospective study. Participants received two intramuscular doses of the vaccine two months apart. Blood was sampled prior to first and 2-6 weeks after the second vaccine dose. Humoral immune response was tested through a chemiluminescence immunoassay (CLIA), using varicella zoster virus glycoprotein E (gE) as the antigen to measure anti-gE levels. The cut-off for the vaccine response assessment was considered an antibody concentration four times higher in the second measure, compared with the first one, according to the results of the clinical trialNCT01165177. The influence of the different treatments on the humoral response to the vaccine was evaluated. JAKi were separated in three groups, according to their mechanism of action: inhibition of JAK 1 (Upadacitinib and Filgotinib), inhibition of JAK 1 and JAK 2 (Baricitinib) and panJAK inhibition (Tofacitinib). Concomitant treatment influence on the humoral response to the vaccine was also determined: classic disease modifying anti-rheumatic drugs (DMARDs) and corticosteroids. The data about adverse events to the vaccination, disease flare or reactivation on HZ infection were collected.ResultsWe enrolled 30 patients, 23 were woman (76,7%), with a mean age of 55±12 years. Fifteen (50%) were under treatment with upadacitinib, eleven (36,7%) with baricitnib, two (6,7%) with filgotinib and two (6,7%) with tofacitinib. Six (20%) had concomitant treatment with methotrexate and 5 (16,7%) with leflunomide. Ten (33%) had low dose prednisone. Four (13%) reported clinically HZ previously.We found that 16 patients (53,3%) reached the response assessment marked initially of quadrupling their initial antibody count. Type of JAKi did not significantly influence the humoral response, neither did the concomitant treatment with disease-modifying antirheumatic drug or low dose glucocorticoid. Fiftheen patients (50%) presented mild adverse effects; 7 (23%) of them consisted in injection-side pain, and 8 (26,7%) were systemic (myalgia, fatigue or fever). One patient (3,3%) had an ischemic cerebrovascular complication 2 weeks after the first dose. None of the patients presented a disease flare in the following 4 weeks postvaccination, neither HZ infection after 7 months of follow-up.ConclusionLightly more than half of the patients (53%) with rheumatic diseases treated with JAKi reached the immune response assessment stablished. In clinical trials with non-rheumatic immunosuppressed patients, the response was ranged between 65-96%. This difference could be explained due to that it is a real-life study and in the type of disease and immunosuppression. Safety and prevention of HZ infection was high. To confirm these results higher number of patients is needed.