# Prospective SARS-CoV-2 additional vaccination in immunosuppressant-treated individuals with autoimmune diseases in a randomized controlled trial

## TL;DR

An additional COVID-19 vaccine improved antibody levels in autoimmune disease patients on immunosuppressants, regardless of whether they paused their medication.

## Contribution

Demonstrated that additional vaccination is effective and safe in immunosuppressed autoimmune disease patients, even without medication withholding.

## Key findings

- Additional vaccination increased anti-RBD concentrations in MMF/MPA and MTX-treated participants regardless of treatment continuation.
- BCDT-treated participants also showed increased anti-RBD concentrations, though lower than MMF/MPA and MTX groups.
- Vaccination was well tolerated with low severe adverse events and mild COVID-19 infections.

## Abstract

Individuals with autoimmune diseases (ADs) on immunosuppressants often have suboptimal responses to COVID-19 vaccines. We evaluated the efficacy and safety of additional COVID-19 vaccines in those treated with mycophenolate mofetil/mycophenolic acid (MMF/MPA), methotrexate (MTX), and B cell–depleting therapy (BCDT), including the impact of withholding MMF/MPA and MTX.

In this open-label, multicenter, randomized trial, 22 participants taking MMF/MPA, 26 taking MTX, and 93 treated with BCDT who had suboptimal antibody responses to initial COVID-19 vaccines (2 doses of BNT162b2 or mRNA-1273 or 1 dose of AD26.COV2.S) received an additional homologous vaccine. Participants taking MMF/MPA and MTX 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 after additional vaccination. Secondary outcomes included adverse events, COVID-19, and AD activity through 48 weeks.

Additional vaccination increased anti-RBD concentrations in participants taking MMF/MPA and MTX, irrespective of immunosuppressant withholding. BCDT-treated participants also demonstrated increased anti-RBD concentrations, albeit lower than MMF/MPA- and MTX-treated cohorts. COVID-19 occurred in 33% of participants; infections were predominantly mild and included only 3 nonfatal hospitalizations. Additional vaccination was well tolerated, with low frequencies of severe disease flares and adverse events.

Additional COVID-19 vaccination is effective and safe in individuals with ADs treated with immunosuppressants, regardless of whether MMF/MPA or MTX is withheld.

ClinicalTrials.gov (NCT05000216; registered August 6, 2021: https://clinicaltrials.gov/ct2/show/NCT05000216).

The NIH/NIAID supported the study through the Autoimmunity Centers of Excellence and the Intramural Research Program

In a clinical trial, additional COVID-19 vaccination was effective and safe in autoimmune patients on immunosuppressants, increasing antibody levels regardless of treatment continuation.