Prospective SARS-CoV-2 Booster Vaccination in Immunosuppressant-Treated Systemic Autoimmune Disease Patients in a Randomized Controlled Trial

Background.Autoimmune disease patients on immunosuppressants exhibit reduced humoral responses to primary COVID-19 vaccination. Booster vaccine responses and the effects of holding immunosuppression around vaccination are less studied. We evaluated the efficacy and safety of additional vaccination in mycophenolate mofetil/mycophenolic acid (MMF/MPA)-, methotrexate (MTX)-, and B cell-depleting therapy (BCDT)-treated autoimmune disease patients, including the impact of withholding MMF/MPA and MTX. Methods.In this open-label, multicenter, randomized trial, 22 MMF/MPA-, 26 MTX-, and 93 BCDT-treated autoimmune disease patients with negative or suboptimal antibody responses to initial COVID-19 vaccines (BNT162b2, mRNA-1273, or AD26.COV2.S) received a homologous booster. MMF/MPA and MTX participants were randomized (1:1) to continue or withhold treatment around vaccination. The primary outcome was the change in anti-Wuhan-Hu-1 receptor-binding domain (RBD) concentrations at 4 weeks post-additional vaccination. Secondary outcomes included adverse events, COVID-19 infections, and autoimmune disease activity through 48 weeks. Results.Additional vaccination increased anti-RBD concentrations in MMF/MPA and MTX patients, irrespective of whether immunosuppression was continued or withheld. BCDT-treated patients also demonstrated increased anti-RBD concentrations, albeit lower than MMF/MPA- and MTX-treated cohorts. COVID-19 infections occurred in 30-46% of participants, were predominantly mild, and included only two non-fatal hospitalizations. Additional vaccination was well-tolerated, with low frequencies of severe disease flares and adverse events. Conclusion.Additional COVID-19 vaccination is effective and safe in immunosuppressant-treated autoimmune disease patients, regardless of whether MMF/MPA or MTX is withheld. Trial Registration. ClinicalTrials.gov (NCT#05000216)