Background: To explore the long-term safety and dynamics of the immune response induced by the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRD) compared with healthy controls. Methods: This international prospective study included adolescents with AIIRD and controls vaccinated with two (AIIRD n=124; controls n=80) or three (AIIRD n=64; controls n=30) doses of the BNT162b2 vaccine, evaluated for vaccine side-effects, disease activity, COVID-19 breakthrough infection rates and severity, and anti-spike S1/S2 IgG antibody titres in a sample from both groups. Results: The vaccination safety profile was favourable, with most patients reporting mild or no side-effects. The rheumatic disease remained stable among 98% and 100% after the second and third doses, respectively. The two-dose vaccine induced comparable seropositivity rates among patients (91%) and controls (100%), (p=0.55), which declined within 6 months to 87% and 100%, respectively (p=0.3), and increased to 100% in both groups, after the third vaccine dose. The overall post-vaccination COVID-19 infection rate was comparable between patients and controls, 47.6% (n=59) and 35% (n=28), respectively; p=0.5278, with most infections occurring during the Omicron surge. In relation to the last vaccination, time-to-COVID-19 infection was similar between patients and controls, at a median of 5.5 vs. 5.2 months, respectively (log-rank p=0.1555). Conclusion: The safety profile of three doses of the BNT162b2 mRNA vaccine was excellent, with an adequate humoral response and similar efficacy among patients and controls. These results support the recommendation for vaccinating adolescents with juvenile-onset AIIRD against COVID-19.

Biologics have revolutionized the treatment of inflammatory arthritis, but their impact on T cell function is unknown. We evaluated the effect of tumor necrosis factor-alpha (TNF-α), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMCs) from PsA patients (n=111) and healthy controls (n=20) were co-cultured with adalimumab (ADA), ixekizumab (IXE), tocilizumab (TCZ), or medium alone for 5 days. T cell activation and proliferation were determined by flow cytometry and cytokines in supernatants were measured by ELISA. Activated CD4+CD25+ T cells were significantly down-regulated by ADA in naïve, conventional disease-modifying anti-rheumatic drug (cDMARD)- and biologic-treated PsA patients compared to medium (p < 0.04, p < 0.01, respectively), IXE, and TCZ. In healthy, ADA reduced the activated CD4+CD25+ T cells proportion but non-significantly as compared to the other groups. Inhibition of PsA patients derived lymphocytes proliferation by the biologics was determined in response to phytohemagglutinin (PHA). The strongest ability to suppress the extent of PHA-induced proliferation was exerted by ADA (p < 0.01) compared to IXE and TCZ. IL-1β, IL-17A, and MMP-3 levels were down-regulated by ADA compared to medium (p < 0.02, p < 0.0001, p < 0.002, respectively). IXE reduced IL-17A (p < 0.0001) but not IL-1β or MMP-3 levels. TNF and IL-17A blockades are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.