AB1298 SAFETY AND EFFICACY OF PRIMARY YELLOW FEVER VACCINATION IN AUTOIMMUNE DISEASE: A PROSPECTIVE CONTROLLED STUDY

Abstract

Background: Alive vaccines should be used with caution in autoimmune diseases (AID).1 Objectives: To evaluate prospectively adverse events and efficacy of the Yellow Fever vaccine in patients with AID. Methods: Prospective study, including 190 individuals, 47 with Rheumatoid Arthritis (RA), 36 primary Sjogren’s Syndrome (SS), 48 Ankylosing Spondylitis (AS), 8 Systemic Sclerosis (SSc), 24 Systemic Lupus Erythematosous (SLE), and 29 Healthy Controls (HC). All individuals received 17DD (Biomanguinhos-FIOCRUZ) YF vaccine, for the first time during the 2017 Brazilian Campaign, aged > 18 years, had no or low disease activity, low immunossupression. Exclusion Criteria: previous vaccination for yellow fever or PRNT > 1:50 at baseline, primary or secondary immunodeficiency, under treatment with cyclophosphamide, chlorambucil, mycophenolate mofetil, calcineurin inhibitors, azathioprine> 2mg/kg/day, prednisone ≥20mg/day, methotrexate >20mg/week or any immunobiological drug. Viremia (CRP) and plaque reduction neutralization test (PRNT; GeoMean title) were measured before (D0) and D3, D4, D5, D6, D7, D14, D28 after vaccine. Adverse events (AE) were registered through patient report diary and medical interview at D7, D14 and D28. Results: Mean age was 52 years old for AID and 56 for HC. No serious adverse event was reported. However, mild local AE was more reported in AID as compared to HC (34.2% vs 3.4%, p=0.000). The frequency of AE was higher in AID compared to HC (34.1 vs. 3.4%). The Risk (Odds Ratio; 95%CI) for AE was 14.53 (1.9-109.7, p=0.000) and AID subgroups: RA=14.5 (1.8-116.2, p=0.0016), AS= 9.3 (1.1-76.2, p=0.0248), SS 25.1 (3.1-204.5, p<0.0001), SLE 9.3 (1.0-84.1, p=0.0377), SSc 56.0 (4.1-769.0, p=0.0014). The PRNT levels expressed in reverse of serum dilution was lower in AID 181 (144-228, p=0.04) as well in AS 112 (73-170, p<0.001), and in SLE 143 (61-332, p=0.01) as compared to HC 440 (291-665). The seropositivity rates were lower in AID after 28 days (78% vs. 96%, p=0.04) as well as in AS (73%, p=0.02) and SLE (73%, p=0.03) as compared to HC (Figure 1). Viremia peak was slightly late and low in AID (D6=5.8 x 103) compared to HC (D5= 8.3 x 103. Seropositivity was statistically lower at D14 in AID as compared HC (21% vs. 75%, p=0.04) and remained lower at D28 in AS and SLE subgroups. Conclusion: Efficacy was lower in AID, especially in SLE and AS, in spite of viremia peak at D5-D6 similar to HC. Taking together, results suggest that YF vaccine is safe in AID with low disease activity and under low immunossupression, but probably a booster dose should be necessary.