Background/Purpose: There is a paucity of data regarding response to vaccinations in patients with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). It is also unclear whether biologic agents affect vaccination response. Data was previously reported on the secondary response to protein vaccination with tetanus. This study investigates the primary response to polysaccharide vaccination in this same cohort.

Methods: Patients with a diagnosis of polyarticular JIA on stable doses of NSAIDS and/or MTX for a minimum of 3 months were enrolled into this prospective study. All patients were naïve to both Pneumovax and Prevnar (7-valent) vaccines. All patients received 0.5 cc Pneumovax (23-valent) subcutaneously. Serum was obtained at vaccination and after 4-6 weeks. 12 Pneumoccocal serotypes were measured (1, 3, 4, 6b, 7f, 8, 9n, 12f, 14, 18c, 19f, 23) by standard EIA. Positive response was considered a 2-fold increase in titer. 200 ng Ab N/mL was considered clinically protective by the clinical laboratory. Serum was subjected to C4 allotyping, immunoglobulin and complement levels to examine alternative causes for non-response. Statistical analysis was performed using parametric and non-parametric methods when appropriate.

Results: 50 patients were included for analysis. 3 additional patients were excluded because of reaction to vaccination requiring steroid treatment. Patients were subdivided into MTX and non-MTX groups for primary analysis. 38 patients were on MTX (n=16 on MTX + etanercept) & 12 patients were on NSAIDS. There was no statistical difference between the 2 groups in the 2-fold response for all serotypes. In addition, there was no difference in 2-fold response in the etanercept+MTX vs MTX vs non-MTX groups. The number of serotypes each group responded to was similar. 39 patients had a response to at least 1 serotype (36 to at least 2). In 11 patients who did not respond, there were no differences in proportion of patients on MTX or etanercept. For each serotype, the pre-dose geometric mean concentrations (GMC) were all greater than 200 ng Ab N/ml. Post immunization GMCs were similar in 9 of 12 serotypes between the MTX and non-MTX groups. Etanercept use did not influence this result. In the other 3 serotypes (1, 6b, 23), the MTX group had significantly higher post-GMCs. There were significant increases in post-GMCs for all serotypes. There was no difference in geometric mean ratio (GMR) for 10 of 12 serotypes between the 2 groups. Of interest, for the other serotypes (1, 18c), the MTX group had a significantly higher GMR when compared to the non-MTX group. Serotype 14 was the most immunogenic (GMR 2.57, 95% CI 1.92, 3.44) while serotype 3 was the least (GMR 1.37, 95% CI 1.08,1.74). Baseline age, MTX dose, or etanercept use did not predict response to pneumococcal vaccine.

Conclusion: In a non-immunized population of patients that were Prevnar naive, with only environmental exposure to Pneumoccocus, use of MTX and etanercept did not diminish humoral response to Pneumovax. All serotypes had post GMCs that were clinically protective. In addition, despite extended use of MTX and etanercept, most patients had protective pre-immunization titers. Future studies will address response to live virus vaccines.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunologic-responsiveness-in-patients-with-juvenile-idiopathic-arthritis-on-methotrexate-and-etanercept-23-valent-pneumococcal-vaccination/