Background Recommendations for vaccination in juvenile idiopathic arthritis mirror recommendations for healthy children except that live attenuated vaccines are withheld from those children treated with most disease modifying anti-rheumatic drugs (DMARDs) and chronic steroids. A new type of vaccine composed of four “vaccine-like particles” (VLPs) was approved for marketing to induce protection against four serotypes of human papilloma virus (HPV) (Gardasil®) in females. For patients on immune suppressive medications, HPV infection may not resolve spontaneously as frequently as in normals, making vaccination in JIA even more important.
Objectives The study was designed to determine the safety and efficacy of immunization with quadrivalent HPV vaccine (Gardasil®) in JIA females who were age 9-26 at study start. Response to vaccine was to be measured by geometric mean titers (GMTs) and compared to population controls. Bio-specimens were to be collected in order to perform future studies aimed at studying mechanism of vaccine response.
Methods Female subjects age 9-26 were recruited according to disease category (polyarticular (poly or sJIA onset), oligo (pauci)-articular onset, and serongative-24 per group planned). ILAR criterion were recorded. Subjects with active systemic JIA (sJIA) (as evidenced by fever, rash and labs) were excluded but SJIA subjects lacking systemic features were permitted to enroll. GMTs were measured at 0, 7, 12 and, where possible 24 months. Blood was collected for post-hoc analyses to be performed if GMTs from patients are found to be lower than age and sex-matched population controls. Adverse events (AEs) and serious adverse events (SAEs) were collected and evaluated at follow up. Subjects with a known history of HPV were excluded.
Results To date, 38 subjects are enrolled. One subject was excluded from GMT analysis because of baseline seropositivity. Of the 28 subjects with baseline and at least one measurement at 7 or 12 months, all but one subject had a rise in titers comparable to population controls in GMTs in response to the four HPV serotypes included in the vaccine. No SAEs were observed AEs observed to date include: URI/sinusitis (8), fever (2), nausea, emesis and/or diarrhea (5), injection site soreness (1), achiness/fatigue/flu (3), lightheadedness/dizziness (4), vasovagal syncope (1), healthy pregnancy >6 months post-last immunization (1), whiplash (1), herpes zoster (1), plantar warts (1), dry socket following wisdom tooth extraction (1), MVA (1), joint pain post-MVA (1), rash/urticaria (2), arthralgia/stiffness (4), arthritis flare (1), enthesitis flare (1), thrush (1), insomnia (1), shortness of breath (1), fatigue (2), strep throat (1), ecchymosis finger (1), otalgia (1).
Conclusions Immunization with quadrivalent HPV vaccine with Gardasil® appears to be safe and induced comparable levels of anti-HPV anitbodies to those observed in control populations in all but one subject to date. Minor disease flare was observed in 2 out of 38 following immunization with Gardasil® but was transient and readily controlled in our study to date.
Acknowledgements Funding for this study has been provided through an IIG from Merck to NGS. The trial is registered as NCT00573651 at Clinical Trials.gov. Merck provided support for GMT measurement that was performed by PPD. The authors thank D. Morus, M. Wallette, K. Krogstad, D. Latham, S. Milhalus, C. Mawhorter, B. Pulova and S. Dawson for study coordination and monitoring and Alfred Saah (Merck) for his support and helpful discussion.
Disclosure of Interest N. Singer Grant/research support: Merck IIG, L. Wagner-Weiner: None declared, K. Nanda: None declared, A. Robinson: None declared, S. Spalding: None declared, H. Bükülmez: None declared