Clinical trial NCT00542776: Impact of Immunosuppression in IBD Patients on Response to Influenza Vaccine
Official title: Impact of Immunosuppression in Patients With Inflammatory Bowel Disease on Responsiveness to Influenza Vaccine
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Disease (IBD)
Immunosuppressed or Non-Immunosuppressed
Influenza Vaccine
Antibody Titers
Seroprotective Titers
Keywords: inflammatory bowel disease (IBD)
immunosuppressed or non-immunosuppressed
influenza vaccine
antibody titers
seroprotective titers
vaccine-associated adverse events
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2007-10-11
Enrollment: 146
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 5 years and older with documented inflammatory bowel disease (Crohn's disease, ulcerative colitis, indeterminate colitis)

Brief summary: The purpose of this study is to compare the efficacy and safety of influenza vaccine in patients with inflammatory bowel disease (IBD) on immunosuppressive therapy with IBD patients on aminosalicylates and healthy historical controls.

Detailed description: Influenza is an extremely contagious airborne disease caused by influenza viruses. It can cause mild to severe illness, and even death. Patients who have inflammatory bowel disease (IBD) have a higher risk of getting serious complications if they are infected. Current guidelines recommend the influenza vaccine for IBD patients. However, many IBD patients take immunosuppressive agents and we are uncertain as to their capacity to mount a truly protective response after vaccination. This is an important area of research because if IBD patients do not have an adequate immunological response, then we may need to enhance their response by increasing the dosage or giving booster shots.

Many clinicians who treat patients with autoimmune diseases are asking if the vaccine is safe and effective. Many IBD patients will receive the vaccine without proper studies being performed to answer these questions. The study we are proposing has important clinical and public health significance. It is a step toward answering the question whether vaccination with the influenza vaccine is safe in patients with IBD and if patients on different types of immunosuppressive medications respond similarly and if they respond as well as healthy controls to the vaccine. There are more than one million people in the United States who have been diagnosed with IBD. Thus, the information gained from this clinical study will provide important knowledge to physicians caring for immunocompromised patients who are considering vaccination.

Studies on the immunological response of immunocompromised patients (e.g., transplant, HIV, oncology, chronic renal failure, SLE) to the influenza vaccine have demonstrated that some of these patients develop antibody titers at a protective level within 4-6 weeks. However, the titers were decreased compared to healthy controls, especially if the immunocompromised patients were on immunosuppressive agents. The frequency of influenza in immunocompromised patients was lower after immunization and there were almost no major side effects from the vaccine.

There is little data on immune response to vaccination in children with IBD. One recently published study compared influenza titers before and after vaccination among 3 pediatric groups: IBD patients who received immunosuppressive therapy, IBD patients who did not receive immunosuppressive therapy, and healthy controls. All IBD patients in the study had a decrease in response to one of three influenza strains when compared to controls. IBD patients who received both immunomodulators and infliximab had a lower immune response rate to two influenza strains when compared to controls. There was no difference in immune response among IBD patients on immunomodulators only, IBD patients on ASA, and controls. There was no difference in rates of adverse events between IBD patients and controls

The primary aim of this research are to measure seroprotection in IBD patients who are on or off immunosuppressive agents after receiving the influenza vaccine. The hypothesis is that IBD patients on immunosuppression have impaired immunity, and therefore, will have a lower seroprotection rate after immunization compared to IBD patients not on immunosuppression. If data is available, we will also compare each group to historical healthy controls given the same vaccine. The secondary aims are to determine the antibody titer levels and side effects these patients have.

The patient population includes IBD patients who are off immunosuppression and IBD patients who are on immunosuppression. Recruiting approximately 75 patients per group will provide adequate power for the study. A blood sample will be taken from all IBD patients to evaluate baseline antibody levels and markers (e.g., CBC, ESR, albumin) before or immediately after immunization with the influenza vaccine. Lab tests will be redrawn at Month 1 (3-8 weeks) to evaluate the level of antibody titers and follow the markers. During the study, we will track basic laboratory measures, disease status by using the Pediatric Crohn's Disease Active Index or Modified Harvey-Bradshaw Score for UC, side effects and adverse events from the vaccinations.

Eligibility criteria: Inclusion Criteria:

1. Crohn's disease, ulcerative colitis, or indeterminate colitis diagnosed by standard clinical, radiographic, endoscopic, and histologic criteria.
2. Age 5 years and older
3. Actively or previously followed by a gastroenterologist at Children's Hospital Boston
4. On non-immunosuppressants (aminosalicylates, antibiotics, or no medications) and/or immunosuppressants (steroids, immunomodulators, TNF-alpha inhibitors) for the past 30 days. Standard concomitant medications (e.g. antihistamines, acetaminophen) will be allowed.

Exclusion Criteria:

1. History of bleeding disorder that would make hematoma likely (eg hemophilia, von Willebrand's disease)
2. Received influenza vaccination during the current influenza season
3. Contraindications to the influenza vaccine (such as severe allergic reaction to prior influenza vaccine)
4. Fever within 48 hr prior to injection
5. Receipt of another vaccination within 2 days of influenza vaccine dose (and no other vaccines planned for 2 days after influenza vaccine)

Primary outcomes:
measure: seroprotection rate
timeFrame: 3-8 weeks after vaccination
Secondary outcomes:
measure: vaccine-associated adverse events
timeFrame: up to 8 weeks after vaccination
measure: antibody titer levels
timeFrame: 3-8 weeks after vaccination
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Ying Lu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blumberg EA, Albano C, Pruett T, Isaacs R, Fitzpatrick J, Bergin J, Crump C, Hayden FG. The immunogenicity of influenza virus vaccine in solid organ transplant recipients. Clin Infect Dis. 1996 Feb;22(2):295-302. doi: 10.1093/clinids/22.2.295.
citation: Soesman NM, Rimmelzwaan GF, Nieuwkoop NJ, Beyer WE, Tilanus HW, Kemmeren MH, Metselaar HJ, de Man RA, Osterhaus AD. Efficacy of influenza vaccination in adult liver transplant recipients. J Med Virol. 2000 May;61(1):85-93.
citation: Banic S, Koren S, Tomazic J, Vidmar L, Ihan A, Poljak M, Avsic-Zupanc A. Influenza vaccination of human immunodeficiency virus 1-infected patients receiving antiretroviral therapy. Acta Virol. 2001 Feb;45(1):39-44.
citation: Matsuzaki A, Suminoe A, Koga Y, Kinukawa N, Kusuhara K, Hara T. Immune response after influenza vaccination in children with cancer. Pediatr Blood Cancer. 2005 Nov;45(6):831-7. doi: 10.1002/pbc.20470.
citation: Cavdar C, Sayan M, Sifil A, Artuk C, Yilmaz N, Bahar H, Camsari T. The comparison of antibody response to influenza vaccination in continuous ambulatory peritoneal dialysis, hemodialysis and renal transplantation patients. Scand J Urol Nephrol. 2003;37(1):71-6. doi: 10.1080/00365590310008749.
citation: Suga T, Niki H, Niikura M, Matsumoto Y, Nishimura T, Nakajima K, Miyazaki M, Endoh M, Nomoto Y, Sakai H. Influenza antibody titers after vaccination of chronic renal failure patients; before and during hemodialysis, or on continuous ambulatory peritoneal dialysis. Tokai J Exp Clin Med. 1990 May;15(2-3):245-51.
citation: Holvast A, Huckriede A, Wilschut J, Horst G, De Vries JJ, Benne CA, Kallenberg CG, Bijl M. Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease. Ann Rheum Dis. 2006 Jul;65(7):913-8. doi: 10.1136/ard.2005.043943. Epub 2005 Dec 1.
citation: Abu-Shakra M, Press J, Varsano N, Levy V, Mendelson E, Sukenik S, Buskila D. Specific antibody response after influenza immunization in systemic lupus erythematosus. J Rheumatol. 2002 Dec;29(12):2555-7.
citation: Mamula P, Markowitz JE, Piccoli DA, Klimov A, Cohen L, Baldassano RN. Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Jul;5(7):851-6. doi: 10.1016/j.cgh.2007.02.035. Epub 2007 Jun 4.