Reactogenicity, safety and disease flares following BNT162b2 mRNA COVID-19 vaccine in patients with chronic immune-inflammatory arthritis treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs

Objectives: The safety of COVID-19 vaccination in rheumatic patients treated with biological (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) remains poorly explored. Methods: Reactogenicity, safety and disease flares following each of the two doses of the BNT162b2 mRNA vaccine was evaluated in 186 patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis treated with b/tsDMARDs, who discontinued anti-rheumatic treatments around vaccination. A group of 53 healthy controls was used for comparison. Results: The frequency and severity of systemic events was similar to that reported in the general population, and no particular safety concerns emerged. The use of methotrexate reduced systemic reactogenicity (adjORs [95% CI] 0.49 [0.25-0.94] and 0.63 [0.32-0.99] after each vaccine dose), whilst no specific effects of different b/tsDMARDs were seen. Flares around vaccination were reported by 24.5% of the patients. Factors associated with flares were active disease (adjORs [95% CI] 2.8 [1.01-8.09] and 1.86 [0.99-6.03] after each vaccine dose) and use of JAKi (adjORs [95% CI] 3.96 [1.39-11.27] and 3.10 [0.99-7.85]). The percentage of cases requiring change or increase in DMARD therapy due to persistent worsening of disease activity at follow-up visits was low (3.2%). Conclusions: The safety of mRNA COVID-19 vaccination in arthritis patients on treatment with b/tsDMARDs is reassuring. In a regimen of peri-vaccine drug interruption, transient flares of the disease more commonly occur in association with active arthritis and use of shorter half-life drugs. Most flares do not require treatment escalation or change.