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Table 1 Sociodemographic characteristics, humoral and cellular responses from cohort 1 (immunosuppressed IMRD ISP+), cohort 2 (immunocompetent IMRD ISP−) and cohort 3 (healthy controls) IMRD ISP+ (immunosuppressed) (n=100) IMRD ISP− (immunocompetent) (n=47) Healthy controls (n=50) P value (cohorts 1/2) P value (cohorts 2/3)
Median age Female (n, %)
66.6 (60.5–75)
68.5 (63–75)
51.2 (32–66)
0.36 0.06
0.09 0.18
60 (60)
36 (77)
32 (64)
Glucocorticoid cumulative dose 9901±1162 Methotrexate cumulative dose 3570±4500
5083±9820 1193±2550
NA NA
0.001* 0.004*
NA NA
Seroconversion rate (n, %) IgG anti-spike (BAU/mL) CD4 T-cell responders (n, %) CD8 T-cell responders (n, %)
55 (55)
38 (80)
50 (100)
0.02*
0.03* 0.18 0.02* 0.04*
254±280
458.6±2960
526.3±2078 0.007*
52 (52) 53 (53)
35 (75) 36 (77)
50 (100) 46 (92)
0.01* 0.01*
BAU, binding antibody unit; IMRD, immune-mediated inflammatory rheumatic disease.
and CD8 T-cell responses was observed in either IMRD group (r=0.70, p<0.001) (figure 2B).
Effect of different immunotherapies on the immunogenicity of the vaccine in patients with IMRD Since decreased vaccine’s immunogenicity was observed in both IMRD cohorts, we next sought to investigate differences that might be due to treatment. Thus, we compared immune responses in patients with IMRD receiving different therapies (table 2). Humoral response The lowest seroconversion rate was observed in patients receiving abatacept (10% of 10 patients) compared with patients with IMRD ISP− ( β =−0.8, 95% IC −1.8 to −0.2, p=0.001) and the rest of patients with IMRD ISP+ ( β =−0.33, 95% IC −0.75 to −0.08, p=0.008). Monotherapy with RTX and BMB was associated with lower seroconver- sion rates than patients with IMRD ISP− ( β =−0.18, 95% IC −0.63 to −0.25, p=0.007 and β =−0.4, 95% IC −0.08 to −0.91, p=0.04, respectively) and the rest of patients with IMRD ISP+ ( β =−0.31, 95% IC −0.72 to −0.09, p=0.03). In the case of RTX, serum IgG levels in patients vacci- nated within 9 months after treatment were below 33.8 BAU/mL in about 75% of patients, but titres increased in correlation with mean time after RTX treatment (r=0.49, p=0.015). Regarding MTX, we found a reduction in anti-spike antibodies (313±291 vs 458.6±2960, p=0.02), and sero- conversion rates (p=0.04) compared with IMRD ISP−, suggesting that MTX modestly impairs humoral response to mRNA-based vaccines. Interestingly, monotherapy with MFM, LFM and AZA did not significantly affect sero- conversion rates. However, antibody titres were dimin- ished with AZA (178.5±142, p=0.01), MFM (323±250,
Figure 2 Correlation between humoral and cellular responses. (A) CD4 T-cell response prediction as a function of humoral response. (B) CD8 T-cell response as a function of CD4 T-cell response.
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Sieiro Santos C, et al . RMD Open 2022; 8 :e001898. doi:10.1136/rmdopen-2021-001898
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