ABSTRACT
Background. Vaccine-induced SARS-CoV-2 antibody responses are reduced in patients taking lymphocyte-depleting therapies, which are commonly prescribed for patients with idiopathic inflammatory myopathies (IIM). While a third vaccine dose (D3) augments the SARS-CoV-2 anti-spike response in some patients, there is a paucity of data on the humoral response following D3 in patients with IIM. Furthermore, the durability of antibody response is unknown. In this study, we evaluated serial antibody response for three months following a 3rd dose SARS-CoV-2 vaccination in IIM patients. Methods. Adults with a patient-reported diagnosis of idiopathic inflammatory myopathy who completed three-dose SARS-CoV-2 vaccination (two-dose BNT162b2 or mRNA-1273 followed by single mRNA or adenoviral vector dose) were recruited via social media campaign. Demographics and clinical characteristics were collected via patient report. Informed consent was provided electronically. Serial antibody responses were evaluated by the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures total antibody to the SARS-CoV-2 S-receptor binding domain (RBD) protein (range 0. 4-2500U/ mL;positive >0.8U/mL). Poor antibody response was defined as anti-RBD titer <500U/mL based on predicted correlates of protective plasma neutralizing capacity. Those with prior COVID-19 infection were excluded. Associations were evaluated using Fisher's exact and Wilcoxon rank-sum tests as appropriate. Results. We evaluated serial anti-RBD titers in 59 participants (Table I). Most (93%) were female with median (IQR) age of 51 (41-62) years. Mycophenolate mofetil was the most frequently prescribed medication (45.6%). Participants completed primary vaccination with two-dose BNT162b2(54%) or mRNA-1273(46%). Median pre-D3 anti-RBD titer (IQR) was 65.8U/mL (4.6,473) at 158 (136-183) days following primary vaccination. Dose 3 included BNT162b2(47%), mRNA-1273(47%) or Ad.26.COV2.S (6%). Most (89.9%) received homologous D3 vaccination. 39% of participants reported holding peri-D3 immunosuppression with mycophenolate mofetil being the most commonly held medication in the peri-D3 period. Repeat anti-RBD testing was performed at a median (IQR) 30 (28-32) days post-D3. A higher antibody titer was seen in 89.9% participants following D3 with median (IQR) titer of 2500 U/mL (92,2500). Thirty-seven percent remained <500U/mL following D3;a greater proportion of these participants reported use of rituximab and greater number of immunosuppressive therapies compared to those with anti-RBD >=500U (72.7% versus 5.4%, p<0.001;3 therapies versus 2 therapies, p=0.03). Furthermore, 13.5% (8/59) remained below the threshold of positivity following D3;7/8 reported use of rituximab, 5/8 mycophenolate mofetil, or combination of these agents (4/8). There was not a significant difference in antibody titers among recipients of homologous/heterologous vaccination (p=0.22). Dose 3 was well tolerated with only 2 (3.4%) participants reporting disease flare requiring treatment within one month of vaccination;neither required intravenous therapy or hospital admission. Thirty-four (57.6%) participants underwent repeat anti-RBD testing three months following D3 with median (IQR) 2500U/mL (456,2500);73.53% (25/34) remained above threshold of >=500U/mL. Limitations of this study include small sample size and absence of healthy control group. Diagnosis was based on participant report and we did not routinely collect information on disease activity. Conclusion. We observed an augmented humoral response in most IIM patients following 3rd dose SARS-CoV-2 vaccination;antibody response was durable at three months. Dose 3 was well tolerated. Over 1/3 participants failed to develop adequate response following D3, namely those on rituximab therapy and on higher number of immunosuppressive therapies. These patients should be prioritized for prophylactic therapies to enhance protection against COVID-19 infection.
ABSTRACT
Background: An attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with rheumatic and musculoskeletal diseases (RMD) (1). We sought to identify clinical factors associated with poor humoral response following primary (two-dose mRNA or single adenoviral vector dose) SARS-COV-2 vaccination in patients with RMD on immunosuppression. Objectives: To identify clinical predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination in RMD patients on immunosuppression. Methods: We included patients ≥18 years old with RMD on immunosuppres-sion who received either two-dose mRNA or single dose Janssen/Johnson and Johnson (J&J) vaccination. Demographics, diagnoses, and therapeutic regimens were collected via participant report;those with prior COVID-19 infection were excluded. One month after vaccination, participants underwent SARS-CoV-2 antibody testing on the semi-quantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures antibody to the SARS-CoV-2 S-recep-tor binding domain (RBD) protein (ceiling >250U/mL later expanded to >2500U/mL). Associations were evaluated using Fisher's exact and Wilcoxon rank sum tests. Logistic regression analyses were performed to evaluate for clinical factors associated with antibody response. We adapted survival methods to address right-truncation of titers;this methodology was used to calculate medians. Participants provided informed consent electronically and the study was approved by the local Institutional Review Board. Results: We studied 1138 RMD participants on immunosuppression;most were female (93%) and white (91%) (Table 1). One-hundred and ffteen (10%) had anti-RBD response in the negative range at a median (IQR) of 29 days (28-34) following completion of vaccine series. A greater proportion of participants with negative response were non-white, received J&J vaccine, reported use of myco-phenolate, rituximab, or glucocorticoids. Antibody response differed by immuno-suppressive regimen, with those receiving rituximab having poorest response (Figure 1). Use of mycophenolate (aOR 9.92, p=0.001), rituximab (aOR 56.99, p=0.001), glucocorticoids (aOR 2.99, p=0.001) or receipt of J&J (aOR 3.13, p=0.039) were associated with negative antibody response. Conclusion: Use of mycophenolate, glucocorticoids, rituximab and receipt of J&J vaccine were the strongest predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination;these data support use of an additional primary dose in RMD patients.