Humoral response to the BNT162b2 second and third vaccine doses
After the second vaccine dose, 37 patients and 23 controls provided serum samples for immunogenicity; 36 patients and 14 controls provided serum samples 6 months later. A total of 9 patients and 9 controls provided samples after the third vaccine. The dynamics of the S1/S2 antibody level among both study groups are presented in Figures 1 and 2. Among the control group, the seropositivity rate was 100% at all three time points. Anti-S1/S2 antibody titres declined at 6 months after the second vaccine from a mean of 388.3 (SD 56.09) BAU/ml to 212.93 (SD 93.69) BAU/ml, and was restored shortly after the third vaccine dose, to 400 (SD 0) BAU/ml. As expected, the seropositivity rate was lower among AIIRD patients compared to controls, 91% at 2-8 weeks and 87% at 6 months after the second vaccination, and returned to 100% following the third dose. Anti-S1/S2 antibody titres declined at 6 months after the second vaccine from a mean of 243.1 (SD 140.8) BAU/ml to 216.9 (SD 157.6) BAU/ml, and increased shortly after the third vaccine dose to 355.8 (SD 126.4) BAU/ml. In comparison to the control group, anti-S1/S2 antibody titres among the patients were significantly lower only at 2–8 weeks after the second vaccine dose (p<0.0001) and comparable at the subsequent 6-month follow-up after the second, and 2-8 weeks after the third dose. Notably, the decline of the anti-S1/S2 antibody titres within 6 months after the second vaccine dose was significantly steeper among the controls compared to patients, with a mean of -197 (SD 87.4) vs. -61.2 (SD 151.4), p=0.0197, respectively. In the limited sample of controls (n=5) and patients (n=2) with available serologic data, the increase in the antibody titre after the third vaccine dose was comparable in both groups.
Patients with JIA maintained the highest level of anti-S1/S2 antibody at all time-points, whereas the lowest anti-S1/S2 antibody levels were found among patients with vasculitis and scleroderma (Supplement Table 2).
Analysis of humoral response according to the use of anti-rheumatic medications showed that patients treated with csDMARDs and bDMARDs developed a comparable humoral response at all points tested. Among 17 patients treated with TNFi, those treated with TNFi monotherapy achieved numerically higher anti-S1/S2 antibody levels than those treated with combination therapy. MMF was most strongly associated with blunted humoral response to vaccination after the second vaccine dose (115± 89). The humoral response following the third vaccine dose evaluated in 2 of 6 patients treated with MMF was completely restored. Notably, 4 patients treated with anti-CD20 therapy (RTX), 2 patients with AAV, 1 patient with SLE, and 1 with systemic sclerosis developed an adequate seropositive response after the second vaccine dose, with the steepest decline in anti-S1/S2 antibody levels within 6 months, compared to antibody kinetics of patients treated with other medications. The humoral response following the third vaccine dose evaluated in one of these patients was completely restored. Patients treated with RTX were vaccinated 6 months after the last RTX dose and before the next dose.