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Randomized Controlled Trial
. 2025 Aug 12;11(3):e005521.
doi: 10.1136/rmdopen-2025-005521.

Immunogenicity of adjuvanted recombinant zoster vaccine in patients with rheumatoid arthritis treated with upadacitinib: 60-week results from a randomised controlled trial substudy

Kevin L Winthrop  1 , Justin Klaff  2 , Sara K Penn  2 , Yanxi Liu  2 , Conrado García  3 , Eduardo Mysler  4 , Alvin F Wells  5 , Xianwei Bu  2 , Irina Fish  2 , Michael Chen  2 , Anthony L Cunningham  6
Affiliations
Randomized Controlled Trial

Immunogenicity of adjuvanted recombinant zoster vaccine in patients with rheumatoid arthritis treated with upadacitinib: 60-week results from a randomised controlled trial substudy

Kevin L Winthrop et al. RMD Open. .

Abstract

Objective: To evaluate the immunogenicity of adjuvanted recombinant zoster vaccine (RZV) in patients with rheumatoid arthritis receiving upadacitinib 15 mg once daily (QD) with background methotrexate.

Methods: Eligible patients in SELECT-COMPARE (NCT02629159) receiving upadacitinib 15 mg QD and background methotrexate received RZV at weeks 0 and 12. Antibody titres were collected at weeks 0, 4, 16 and 60 (prevaccination, 4 weeks after first dose, and 4 and 48 weeks after second dose). The primary endpoint was the proportion of patients achieving a satisfactory humoral response to RZV at week 16 (≥ 4-fold increase in prevaccination anti-glycoprotein E (gE) antibody titres). Cell-mediated immune (CMI) response to RZV (≥ 2-fold increase in prevaccination gE-specific CD4+ [2+] T-cell frequency) was assessed at each time point in a subcohort of 38 patients. Safety was assessed for 30 days after each vaccination.

Results: Overall, 93 patients received both RZV doses (78.5% female; mean age, 62.4 years). At baseline, 49.5% used concomitant corticosteroids (median daily dose, 5.0 mg). Satisfactory humoral responses to RZV were observed in 87.8% (95% CI 81.0 to 94.5) of patients at week 16. Age and concomitant corticosteroid use did not affect RZV antibody response. Over 60% of patients achieved a CMI response to RZV at all time points. No serious adverse events were reported. One patient developed herpes zoster 4 months after the second RZV dose.

Conclusions: Most patients receiving upadacitinib 15 mg QD with background methotrexate achieved satisfactory humoral and CMI responses 4 weeks after the second RZV vaccination (week 16).

Keywords: Antirheumatic Agents; Arthritis, Rheumatoid; Vaccination.

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Conflict of interest statement

Competing interests: KLW has received consulting fees and/or research grants from AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, Pfizer, Roche and UCB. CG has received medical fees to serve as principal investigator in AbbVie clinical trials. EM has received or has pending grants from Bristol Myers Squibb, Novartis, Pfizer and Roche. He has received honorarium from AbbVie, Amgen, AstraZeneca, GSK, Lilly, Pfizer, Roche, Sandoz and Sanofi; has provided writing assistance, medicines, equipment or administrative support to AbbVie, Pfizer and Roche; and has received payment for lectures including service on speakers bureaus from AbbVie, Alpine Immunology, Amgen, AZ, GSK, Hi Bio, Janssen, Lilly, Pfizer, Roche, Sandoz and Sanofi. AW has received honoraria from AbbVie, Amgen, Bristol Myers Squibb, Lilly, Novartis, Pfizer and Sanofi. ALC has received honoraria paid to his institution from AbbVie, BioCSL/Seqirus, GSK and Moderna. JK, SKP, YL, XB, IF and MC are full-time employees of AbbVie and may hold AbbVie stock or stock options.

Figures

Figure 1
Figure 1. Vaccine substudy design. aNumber of patients who received ≥1 RZV dose. csDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs; QD, once daily; RZV, adjuvanted recombinant zoster vaccine.
Figure 2
Figure 2. Proportion of patients achieving satisfactory humoral responses to RZV at weeks 4, 16 and 60. Error bars indicate 95% CI. Satisfactory humoral response was defined as a ≥4-fold increase in the concentration of anti-glycoprotein E antibody titres compared with the prevaccination concentration (week 0). The number of patients was based on the availability of blood samples collected at baseline and the substudy visits. RZV, adjuvanted recombinant zoster vaccine.
Figure 3
Figure 3. (A) The effect of age, (B) baseline concomitant CS use, (C) baseline concomitant CS dose and (D) baseline RA disease severity on humoral responses to RZV at weeks 16 and 60. Error bars indicate 95% CI. Satisfactory humoral response was defined as a ≥4-fold increase in the concentration of anti-glycoprotein E antibodies compared with the prevaccination concentration (week 0). The number of patients was based on the availability of blood samples collected at baseline and the substudy visits. Disease severity was classified by the CDAI. CS, corticosteroid; CDAI, Clinical Disease Activity Index; RA, rheumatoid arthritis; RZV, adjuvanted recombinant zoster vaccine.
Figure 4
Figure 4. GMFR in prevaccination anti-gE antibody levels at weeks 4, 16 and 60 after RZV vaccination. Error bars indicate 95% CI. The number of patients was based on the availability of blood samples collected at baseline and the substudy visits. gE, glycoprotein E; GMFR, geometric mean fold rise; RZV, adjuvanted recombinant zoster vaccine.
Figure 5
Figure 5. (A) Cell-mediated immune responses to RZV and (B) GMFR in prevaccination gE-specific CD4+ [2+] T-cell levels at weeks 4, 16 and 60. Error bars indicate 95% CI. Responders for cell-mediated immune response (figure 5A) were patients with a ≥2-fold increase in the frequencies of gE-specific CD4+ [2+] T cells compared with the prevaccination frequencies. A technical cut-off was assigned to non-positive frequency values of gE-specific CD4+ [2+] T cells to calculate the fold rise. The number of patients was based on the availability of blood samples collected at baseline and the substudy visits. gE, glycoprotein E; GMFR, geometric mean fold rise; RZV, adjuvanted recombinant zoster vaccine.
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