ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0457

Immunosuppression Attenuates Antibody and Neutralization Titers in Patients with Chronic Inflammatory Disease Following SARS-CoV-2 Vaccination

Michael Paley1, Parakkal Deepak2, Wooseob Kim2, Monica Yang3, Alex Carividi3, Emanuel Demissie3, Alia A. El-Qunni,2, Alem Haile2, Katherine Huang2, Baylee Kinnett2, Mariel Liebeskind2, Zhouming Liu2, Lily E. McMorrow2, Diana Paez3, Niti Pawar3, Dana Perantie2, Rebecca E. Schriefer2, Shannon Sides2, Mahima Thapa2, Sewuese Akuse4, Samantha Burdess2, Abbey Rose2, Lynne Mitchell2, Salim Chahin2, Matthew Ciorba2, Jonathan Graf5, Patricia Katz3, Mehrdad Matloubian3, Jane O'Halloran2, Rachel Presti2, Gregory Wu2, Sean Whelan2, William Buchser2, Lianne Gensler6, Mary Nakamura7, Ali H Ellebedy2 and Alfred Kim2, 1Washington University in St. Louis, Olivette, MO, 2Washington University School of Medicine, St. Louis, MO, 3University of California San Francisco, San Francisco, CA, 4Washington University School of Medicine, St Louis, MO, 5Ucsf, San Francisco, CA, 6Department of Rheumatology, University of California San Francisco, San Francisco, CA, 7UCSF/SFVAHCS, San Francisco, CA

Meeting: ACR Convergence 2021

Keywords: , ,

Session Information

Date: Saturday, November 6, 2021

Title: Plenary I (0453–0457)

Session Type: Plenary Session

Session Time: 11:45AM-12:00PM

Background/Purpose: Individuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in these patients is essential to risk-stratify them with impaired protection and provide clinical guidance regarding medication management.

Methods: We initiated the COVID-19 Vaccine Responses in Patients with Autoimmune Disease (COVaRiPAD) study, a prospective assessment of mRNA-based vaccine immunogenicity and reactogenicity in patients with CID. We collected blood from 197 adults with CIDs and 53 immunocompetent controls before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+ binding and neutralizing antibody titers were quantified to assess the magnitude and quality of the humoral response following vaccination.

Results: Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.0046) and SARS-CoV-2 neutralization (P< 0.0001) to the D614G common variant were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 13-fold reduction in humoral responses, respectively (p< 0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analyses (P< 0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization.

Conclusion: CID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses. We are currently determining cross-variant neutralization, long-term antibody and neutralization titers, and T cell responses in this cohort.

Table 1. Demographic and Clinical Characteristics of Participants with Chronic Inflammatory Diseases

Figure 1

Disclosures: M. Paley, None; P. Deepak, Abbvie, 1, Takeda Pharmaceuticals LLC, 5, Janssen Pharrmaceuticals, 1, Pfizer, 1, Prometheus Biosciences, 1, Boehringer Ingelheim, 1, 5, Arena Pharmaceuticals, 1, 5, Bristol-Myers Squibb-Celgene, 5; W. Kim, None; M. Yang, None; A. Carividi, None; E. Demissie, None; A. El-Qunni,, None; A. Haile, None; K. Huang, None; B. Kinnett, None; M. Liebeskind, None; Z. Liu, None; L. McMorrow, None; D. Paez, None; N. Pawar, None; D. Perantie, None; R. Schriefer, None; S. Sides, None; M. Thapa, None; S. Akuse, None; S. Burdess, None; A. Rose, None; L. Mitchell, None; S. Chahin, None; M. Ciorba, Abbvie, 2, Pfizer, 2, 5, BMS, 2, Theravance, 2, Incyte, 5, Janssen, 5; J. Graf, None; P. Katz, None; M. Matloubian, Virtuoso Therapeutics Inc., 2; J. O'Halloran, None; R. Presti, None; G. Wu, Novartis, 2, Genentech, 2, Biogen, 5, EMD Serono, 5, Roche, 5; S. Whelan, Vit Biotechnology, 5, Abbvie, 5, SAb Therapeutics, 5; W. Buchser, None; L. Gensler, Novartis, 5, UCB, 5, Eli Lilly, 2, Gilead, 2, Pfizer, 2, Pfizer, 5, Janssen, 2, UCB, 2; M. Nakamura, None; A. Ellebedy, Emergent BioSolutions, 5, Abbvie, 5; A. Kim, Kypha, Inc., 5, GlaxoSmithKline, 2, 5, 6, Alexion Pharmaceuticals, 2, Annexon Biosciences, 2, Aurinia Pharmaceuticals, 2, 6.

To cite this abstract in AMA style:

Paley M, Deepak P, Kim W, Yang M, Carividi A, Demissie E, El-Qunni, A, Haile A, Huang K, Kinnett B, Liebeskind M, Liu Z, McMorrow L, Paez D, Pawar N, Perantie D, Schriefer R, Sides S, Thapa M, Akuse S, Burdess S, Rose A, Mitchell L, Chahin S, Ciorba M, Graf J, Katz P, Matloubian M, O'Halloran J, Presti R, Wu G, Whelan S, Buchser W, Gensler L, Nakamura M, Ellebedy A, Kim A. Immunosuppression Attenuates Antibody and Neutralization Titers in Patients with Chronic Inflammatory Disease Following SARS-CoV-2 Vaccination [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/immunosuppression-attenuates-antibody-and-neutralization-titers-in-patients-with-chronic-inflammatory-disease-following-sars-cov-2-vaccination/. Accessed .

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