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. 2025 Nov 25:e191266.
doi: 10.1172/jci.insight.191266. Online ahead of print.

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

Meggan Mackay  1 , Catriona A Wagner  2 , Ashley Pinckney  3 , Jeffrey A Cohen  4 , Zachary S Wallace  5 , Arezou Khosroshahi  6 , Jeffrey A Sparks  7 , Sandra Lord  8 , Amit Saxena  9 , Roberto Caricchio  10 , Alfred Hj Kim  11 , Diane L Kamen  12 , Fotios Koumpouras  13 , Anca D Askanase  14 , Kenneth Smith  2 , Joel M Guthridge  2 , Gabriel Pardo  2 , Yang Mao-Draayer  2 , Susan Macwana  2 , Sean McCarthy  15 , Matthew A Sherman  15 , Sanaz Daneshfar Hamrah  15 , Maria Veri  15 , Sarah Walker  3 , Kate York  3 , Sara K Tedeschi  7 , Jennifer Wang  16 , Gabrielle E Dziubla  16 , Mike Castro  16 , Robin Carroll  16 , Sandeep R Narpala  16 , Bob C Lin  16 , Leonid Serebryannyy  16 , Adrian B McDermott  16 , William T Barry  3 , Ellen Goldmuntz  15 , James McNamara  15 , Aimee S Payne  17 , Amit Bar-Or  17 , Dinesh Khanna  18 , Judith A James  2
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Free article

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

Meggan Mackay et al. JCI Insight. .
Free article

Abstract

Background: Individuals with autoimmune diseases (AD) on immunosuppressants often have suboptimal responses to COVID-19 vaccine. 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.

Methods: 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 post-additional vaccination. Secondary outcomes included adverse events, COVID-19 , and AD activity through 48 weeks.

Results: 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 three 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 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).

Keywords: Autoimmune diseases; Autoimmunity; COVID-19; Clinical practice; Rheumatology; Vaccines.

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