2273: Waning Vaccine Response After Primary Vaccine Series: Results from the Covid19 Vaccine Response in Rheumatology Patients (COVER) Study

Amy Mudano¹, Gary Cutter², Ted Mikuls³, Geoffrey Thiele⁴, Mark Law⁴, Bart Hamilton⁴, Michael Zikry⁵, Kelly Y. Chun⁶, Monique Bastidas⁷, Michael George⁸, Lisa Williams⁹, Kevin Winthrop¹⁰, Mark Busch¹¹, Stanley Cohen¹², Roman Czubatyj¹³, Rajesh Kataria¹⁴, Reshma Khan¹⁵, Soha Mousa¹⁶, Jose Pando¹⁷, Elizabeth Perkins¹⁸, Shanmugapriya Reddy¹⁹, Delfin Santos²⁰, Joy Schechtman²¹, Frank Scott²², Sucharitha Shanmugam²³, Atul Singhal²⁴, John Tesser²⁵, John Tower²⁶, Swamy Venuturupalli²⁷, Sean Joseph Wollaston²⁸, Conrad Ziembinski²⁹ and Jeffrey Curtis³⁰, ¹Illumination Health, Hoover, AL, ²University of Alabama at Birmingham, Birmingham, AL, ³Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, ⁴University of Nebraska Medical Center, Omaha, NE, ⁵LabCorp, Burlington, NC, ⁶Labcorp, Calabasas, CA, ⁷LabCorp, Northridge, CA, ⁸University of Pennsylvania, Philadelphia, PA, ⁹Illumination Heath, Hoover, AL, ¹⁰Oregon Health & Science University, Portland, OR, ¹¹Family Arthritis Center-Jupiter, Jupiter, FL, ¹²Metroplex Clinical Research Center, Pittsburgh, PA, ¹³Arthritis Physicians LLC, Rochester Hills, MI, ¹⁴Southern Ohio, Wheelersburg, OH, ¹⁵Palm Beach Rheumatology and Wellness, Jupiter, FL, ¹⁶Arthritis and Rheumatology of Southwest Ohio, Liberty Township, OH, ¹⁷Rheumatology Consultants of DE, Lewes, DE, ¹⁸Rheumatology Care Center, Hoover, AL, ¹⁹Southwest Florida Rheumatology, Riverview, FL, ²⁰Rochester Rheumatology, Rochester Hills, MI, ²¹SunValley Arthritis Center, Peoria, AZ, ²²Arthritis Medical Center, Arroyo Grande, CA, ²³Rheumatology and Arthritis Care Center, Exton, PA, ²⁴Southwest Rheumatology Research, Mesquite, TX, ²⁵Arizona Arthritis & Rheumatology Associates, Phoenix, AZ, ²⁶Arthritis Physicians LLC, Rochester, MI, ²⁷Cedars-Sinai Medical Center, Los Angeles, CA, ²⁸Rheumatology Associates, North Hollywood, CA, ²⁹CZ Rheumatology, Coral Springs, FL, ³⁰Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL

Background/Purpose: Given possible increased risk of COVID-19 in patients with autoimmune conditions, there is a need to better understand the immunogenicity and safety of SARS-CoV-2 vaccines in people living with rheumatic disease. We are currently conducting the Covid VaccinE Response (COVER) trial, a multicenter, randomized controlled trial to evaluate the response to a SARS-CoV-2 booster in patients with confirmed rheumatic disease on immunomodulatory therapies. In this analysis, we examined response to the primary mRNA vaccine series in relation to the time since vaccination, and therapy.

Methods: COVER randomizes rheumatoid arthritis (RA) or spondyloarthritis (SpA) patients in a large practice-based research network of U.S. rheumatologists to continue their current immunomodulatory therapy regimen or briefly interrupt (ie, hold for 2 weeks) following administration of a 3^rd or 4^th dose (booster) of SARS-CoV-2 vaccine. In this analysis, baseline vaccine response was examined cross-sectionally in relation to time since the primary vaccine series. LabCorp Cov2Quant IgG™ Spike assay was used to measure levels of anti-Receptor Binding Domain (RBD) IgG antibodies in response to vaccination and or/natural infection. Anti-Nucleocapsid antibodies were measured to identify prior SARS-CoV-2 infection and evidence of prior COVID-19 infection was also classified using self-report. Demographic characteristics were reported, and COVID-19 RBD antibody levels examined in relation to time since primary vaccination. Linear regression was used to evaluate determinants of mean log anti-RBD antibody titers and compared by drug categories.

Results: A total of 352 participants completed a baseline visit and were eligible for analysis (Table 1). Participants were 75% women, 90% white, 20% Hispanic. Mean age: 57.4 (13.8), mean BMI 32.2 (9.4). The majority had RA (77%); 46% TNFi use, 28% JAKi, 27% others (abatacept, IL-17i) at primary vaccine series. Among those with no prior COVID-19 infection, anti-RBD IgG antibody titers showed a clear decrease with time since receipt of prior vaccination (Figure 1). In adjusted linear regression, referent to TNFi, JAKi (p=0.02) and abatacept (p=0.05) patients had lower mean titers, even after accounting for time since vaccine, number of vaccine doses and Anti-Nucleocapsid status. Table 2 shows the comparison of anti-Nucleocapsid status at baseline with participant self-report of prior COVID-19 infection, specificity was 78% (95% CI: 72%-83%) and sensitivity was 65% (55%-73%).

Conclusion: A clear decrease of anti-RBD IgG antibody levels in patients with RA or SpA taking immunomodulatory therapy was seen with increasing time following previous vaccine receipt. This effect was more pronounced in those who reported no prior COVID-19 infection, and who were receiving JAKi or abatacept (referent to TNFi). Self-report of prior COVID infection substantially misclassified prior COVID-19 infection and may confound immunogenicity outcomes in vaccine studies. Future analysis of the randomized trial results will look at the effect of holding or continuing immunomodulatory treatment at the time a SARS-CoV-2 booster is given.





Disclosures: A. Mudano, None; G. Cutter, AI Therapeutics, AMO Pharma., Astra-Zeneca,, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring,, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Pharmaceuticals, mmunic, Mapi Pharmaceuticals LTD, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics, Prothena Biosciences, Novartis, Regeneron,, Sanofi-Aventis, Reata Pharmaceuticals, Alexion, Antisense Therapeutics, Biogen, Clinical Trial Solutions LLC, Genzyme, Genentech, GW Pharmaceuticals/Jazz, Klein-Buendel Incorporated, Merck/Serono, Osmotica Pharmaceuticals, Perception Neurosciences, Protalix Biotherapeutics,, Recursion/Cerexis Pharmaceuticals, Roche, SAB Biotherapeutics; T. Mikuls, Gilead Sciences, Bristol-Myers Squibb, Horizon, Sanofi, Pfizer Inc; G. Thiele, None; M. Law, None; B. Hamilton, None; M. Zikry, Labcorp, labcorp; K. Chun, None; M. Bastidas, LabCorp; M. George, AbbVie, GlaxoSmithKlein(GSK), Chemocentryx; L. Williams, None; K. Winthrop, AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer, Roche, Regeneron, Sanofi, UCB, AstraZeneca, Novartis; M. Busch, Amgen, AbbVie/Abbott, GlaxoSmithKlein(GSK), UCB, horizon; S. Cohen, AbbVie/Abbott, Amgen, Gilead, Eli Lilly, Pfizer; R. Czubatyj, AbbVie/Abbott, Amgen, Horizon, Exagen, Janssen; R. Kataria, AbbVie/Abbott, Amgen, Horizon, Scipher; R. Khan, Amgen, Janssen, GlaxoSmithKlein(GSK); S. Mousa, None; J. Pando, AbbVie/Abbott, Novartis; E. Perkins, AbbVie/Abbott, Novartis, Janssen; S. Reddy, AbbVie/Abbott, Amgen, Bristol-Myers Squibb(BMS), Janssen, Novartis, Pfizer, UCB; D. Santos, Pfizer, Amgen, AbbVie/Abbott; J. Schechtman, Exagen, Mallinckrodt, Horizon, Pfizer, UCB, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Lilly, Myriad, Boehringer-Ingelheim, Genentech, Scipher, Janssen, Radius, Amgen, ChemoCentryx; F. Scott, None; S. Shanmugam, AstraZeneca; A. Singhal, None; J. Tesser, AbbVie, Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb (BMS), Eli Lilly, GlaxoSmithKlein (GSK), Janssen, Gilead, Merck/MSD, Novartis, Pfizer, UCB, Aurinia, Genentech, Sanofi-Genzyme, Biogen, Celgene, CSL Behring, Horizon, R-Pharma, Regeneron, Roche, Sandoz, Scipher, Takeda, Sun Pharma, Selecta, Vorso; J. Tower, Amgen; S. Venuturupalli, Horizon Pharma USA, Inc., Kezar Life Sciences, Inc., Mallinckrodt, Inc., Navidea Biopharmaceuticals, Inc., Pfizer (Current), Bristol-Myers Squibb(BMS), Argenx, Janssen; S. Wollaston, None; C. Ziembinski, UCB, Scipher, CorEvitas; J. Curtis, Amgen, Bristol-Myers Squibb (BMS), CorEvitas, IlluminationHealth, Janssen, Lilly, Myriad, Novartis, Pfizer, Sanofi, UCB, Aqtual, Bendcare, FASTER, GlaxoSmithKlein (GSK), Labcorp, Scipher, Setpoint, United Rheumatology, AbbVie, ArthritisPower.