Previous Biologic DMARD Use Lowers Yellow Fever Vaccine Response in Spondyloarthritis

Researchers sought to determine whether previous use of biologic DMARDs impacted the overall performance of 17DD-YF vaccination in patients with spondyloarthritis.

Previous use of biologic disease-modifying antirheumatic drugs (bDMARD) lowered immune responsiveness to 17DD-YF vaccination for yellow fever (YF) in patients with spondyloarthritis (SpA), according to study findings published in Vaccine.

Researchers conducted a prospective, non-interventional study between March and July 2017 of 51 patients with SpA and 23 healthy control participants to determine whether bDMARD use impacted patient immune response to 17DD-YF vaccination.

Of the 51 patients with SpA, 26 (51%) used bDMARDs without immunosuppression or non-biologic immunotherapy, including non-steroidal anti-inflammatory drugs (NSAIDs), prednisone, methotrexate, leflunomide, and sulfasalazine, while 25 (49%) patients reported a history of previous biologic immunotherapy, including adalimumab, etanercept, and infliximab.

The researchers collected serum samples prior to and following 17DD-YF vaccination at 8 different time points on days 0 (baseline prior to vaccination), 3, 4, 5, 6, 7, 14, and 28. Serum analysis of each patient’s immune response to vaccination included titration of YF-specific neutralizing antibodies, quantification of YF viremia, and concentrations of immunological biomarkers such as chemokines, pro-inflammatory cytokines, regulatory cytokines, and growth factors.

Patients in the SpA group demonstrated decreased titers of YF-specific neutralizing antibodies compared with the control group (P <.0001). They also demonstrated a 73% seropositivity rate after 28 days compared with the 96% seropositivity rate in the control group (P =.0221). Patients in the biologic group had lower seroconversion rates compared with controls (64% vs 96%; P =.0070), whereas the immune response rate was similar in the non-biologic immunotherapy and control groups (81% vs 96%; P =.112).

Patients in the SpA group who either used biologic or non-biologic immunotherapies exhibited lower YF-specific neutralizing antibody titers compared with controls 28 days after vaccination (P < .0001). The researchers did not observe any difference in neutralizing antibody titers between patients using non-biologic versus biologic immunotherapies, or any differences in YF viremia throughout all subgroups.

Patients with SpA did not report significant changes in disease activity up to 6 months following 17DD-YF vaccination per Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, which remained comparable to baseline scores.

Serum concentrations of immunological biomarkers were higher at baseline and throughout the post-vaccination time points in the SpA biologic group and in those whose BASDAI scores were 4 or greater compared with those in the non-biologic immunotherapy group and those with BASDAI scores less than 4.

Limitations of the study included a lack of analysis of cellular immune response and a lack of sex- and age-matched controls, as female sex has been found to impact vaccine-induced immunity.

The study authors concluded, “[T]hese findings suggested that the use of [bDMARDs] impacts the response to the 17DD-YF vaccine, even after planned washout…. [P]revious [bDMARD] therapy, the inflammatory status prior to vaccination, and impairment of the IFN-ϒ/IL-10 axis at the peak of viremia may determine the immunogenicity of 17DD-YF vaccination in patients with SpA.”


Casagrande TZ, Costa-Rocha IA da, Gavi MBR de O, et al. Previous biological therapy and impairment of the IFN-γ/IL-10 axis are associated with low immune response to 17DD-YF vaccination in patients with spondyloarthritis. Vaccine. Published online June 18, 2022:S0264-410X(22)00703-4. doi:10.1016/j.vaccine.2022.05.071