Background: Female patients receiving immunosuppressive therapy may be at increased risk for human papillomavirus (HPV) infection and cervical neoplasia.
Methods: We administered the 3-dose HPV vaccine Gardasil to 37 females aged 9 to 26 years with inflammatory bowel disease (IBD) prescribed immunosuppressive therapy (prospective cohort). Geometric mean titers (GMT) in milli-Merck (mMu/mL) units were determined before dose 1 and 1 month after dose 3 by competitive Luminex immunoassay (cLIA) and qualitatively compared with healthy females of similar age from Merck’s database. Side effects and adverse events were evaluated. Concurrently, in 15 similar patients with inflammatory bowel disease previously vaccinated by their primary care provider, we assessed antibody titers by competitive Luminex immunoassay and total immunoglobulin G LIA after dose 3 of vaccine (range, 0.5–27 months).
Results: Mean age of prospective patients was 15 years with 51% on anti–tumor necrosis factor therapy and 49% on immunomodulators: 33 of 37 completed all 3 doses. Seropositivity after dose 3 was 100% for types 6, 11 and 16 and 96% for type 18. Geometric mean titers for HPV-6, HPV-11, HPV-16 and HPV-18 was 1080, 1682, 3975 and 858, respectively and did not qualitatively differ from healthy females. No serious adverse events were attributable to the vaccine. In the previously vaccinated cohort, seropositivity was 100% for types 6, 11, and 16, and 40% for type 18 by competitive Luminex immunoassay (93% for HPV-18 by immunoglobulin G LIA). Titers decreased with time since dose 3.
Conclusions: In this small study of patients with inflammatory bowel disease prescribed immunosuppressive therapy, Gardasil was immunogenic and there were no clinically significant vaccine-associated adverse events.
Article first published online 4 April 2013
*Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts;
†Division of Gastroenterology, Hepatology and Nutrition, Inflammatory Bowel Disease Center, Boston Children’s Hospital, Boston, Massachusetts;
‡Pediatric Gastroenterology, Maine Pediatric Group, Portland, Maine;
§Division of Adolescent/Young Adult Medicine;
‖Division of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts; and
¶Division of Pediatric Gastroenterology and Nutrition, Cohen Children’s Medical Center, New Hyde Park, New York.
Reprints: Denise Jacobson, PhD, MPH, Center for Biostatistics in AIDS Research, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115 (e-mail: firstname.lastname@example.org).
Supported by an investigator-initiated grant from Merck and Co., Inc. (IISP 33063), a grant for Training in Pediatric Gastroenterology and Nutrition (T32DK07477), and MO1-RR02172 from the National Center for Research Resources, National Institutes of Health to the Children's Hospital Boston General Clinical Research Center. The sponsor, Merck and Co, Inc. assisted in study design, measured all of the titers, and provided some references to aid in interpretation of some of the results and saw the final manuscript.
The current study was an investigator-initiated protocol written by Drs. Jacobson, Lu and Bousvaros, and research support was provided by Merck and Co., Inc. During the same time the study was conducted, Dr. Bousvaros was a site investigator for studies sponsored by UCB pharmaceuticals, Abbott pharmaceuticals, and a consultant to Millenium Pharmaceuticals.
Received September 20, 2012
Accepted September 22, 2012