(AQ) Vaccination and Acute Flares in Rheumatoid Arthritis: A Nationwide Case-Crossover Study Using the French SNDS Health Care Databases

Publication Number: 1041

Background: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune disease. Patients with RA have a significant increased risk of serious infection following treatment with disease-modifying antirheumatic drugs, and clinical guidelines strongly recommend pneumococcal and influenzae vaccines; recurring allegations on their association with disease incidence are raised. The role of vaccination on the occurrence of flares of the disease is not fully known. Associations with vaccines have been reported, such as those against tetanus, hepatitis B, and influenza, but causality has not been confirmed.

Objectives: This study aimed the association between vaccination and the occurrence of acute flares in patients diagnosed with RA.

Methods: A case-crossover study was conducted within a cohort of RA. All patients with a diagnosis of RA were identified between 1st Jan. 2008 and 31st Dec. 2018 in a nationwide linked health care database covering 97% of the French population. A RA flare was defined as either a new pharmacy dispensing claim for high-dose corticosteroid or hospitalization with an RA-related primary discharge diagnosis (ICD-10 codes). Vaccine exposure in the 2 months prior to the date of flare (risk window) was compared with prior exposure in up to 4 control time windows per patient (each of 2 months). GEE models were used to account for the occurrence of multiple flares within an individual, adjusting for health care utilization. Stratification by first or subsequent flares and by type of vaccine (bacterial or viral) was conducted.

Results: A total of 223,612 patients with RA were identified. The mean age of patients at study entry was 56.1 years [SD:14.8] and 72.6% were females. A total of 799,634 acute RA flares were identified over the study period, among which 79,417 (9.9%) were first episodes in incident RA patients. Overall, 81.9% of RA patients were vaccinated at least once during the study period, distributed as follows (non-mutually exclusive): vaccine combinations (46.1%), flu (53.0%), pneumococcus (41.7%), hepatitis B (2.4%), tetanus (5.9%) and others ( < 1%). In patients with prevalent flares, 57,218 (7.49%) vaccinations occurred during the risk window compared to 168,234 (7.11%) occurring in the control windows (odds ratio (OR): 1.13; 95% confidence interval (CI): [1.12-1.14]). The OR for viral vaccines was OR=1.19 [1.18 - 1.21]), for bacterial vaccines OR=0.96 [0.94 – 0.98] and for combinations: OR= 0.93 [0.91-0.96]. Findings were similar for incident flares.

Conclusions: From this large-scale study, we observed a small association between vaccination and flares in RA patients. Further research is needed to confirm this association notably the role of circulating viral epidemics and disease activity on vaccination and flares.