Hepatitis B Virus Immunity Often Compromised in Pediatric Patients on Biologics for Inflammatory Bowel Disease
October 21, 2010 (San Antonio, Texas) — Children with inflammatory bowel disease (IBD) who have been vaccinated against hepatitis B virus (HBV) still might not carry adequate antibodies to protect them from infection. This appears to be due to biologic therapy for IBD, according to research presented here at the American College of Gastroenterology 2010 Annual Scientific Meeting and Postgraduate Course.
Biologic drugs, such as infliximab, although considered revolutionary in their ability to treat IBD, are potent immunosuppressants and can reactivate hepatitis B in chronic carriers of the disease. Now it appears that they can also block the effectiveness of HBV immunization.
An evaluation of 100 children who were being treated with infliximab for IBD, including 61 who had received an HBV vaccination, indicated that as many as 33 (54%) of the vaccinated children did not have adequate HBV immunity, defined as 10 mIU/mL or more of antibodies to the hepatitis B surface antigen (anti-HBs).
"First, we showed that no one was a chronic carrier, so that was good, but about half of the children who had been vaccinated for hepatitis B did not have adequate immunity against the disease," said Naim Alkhouri, MD, a coauthor on the study and a gastroenterology fellow at The Cleveland Clinic in Ohio.
"That's very concerning because these patients were on immunosuppressant therapy, and therefore could be at a higher risk for reactivation if they had been chronic carriers, or could be at a greater risk for complications and becoming acutely infected."
The mean age of patients in the study was 17.8 years, and none were positive for the surface antigen of HBV or the antihepatitis B core antigen. The mean concentration of anti-HBs in immune patients was 295.6 ± 350.6 mIU/mL.
The presence of pancolitis and lower albumin levels due to IBD were associated with greater loss of hepatitis B immunity; for each 0.5 g/dL decrease in albumin levels, the likelihood of losing immunity was increased by 62%.
The concurrent use of infliximab, however, did not affect immunity levels, nor did dose or duration. Immunity appears to have been established prior to the initiation of immunosuppressant therapy in the children who exhibited HBV immunity.
"We initially thought that if you were on a higher dose or were taking the drugs more frequently, it could affect your immunity, but we found that that was not the case," said Dr. Alkhouri.
Dr. Alkhouri and his team are now looking into the effect of vaccinating patients with boosters when they are already taking immunosuppressants.
"There is evidence that you do not respond the same way if you are immunosuppressed, so our next step will be to determine the effects of vaccination while on infliximab."
The findings underscore that need to check IBD patients' hepatitis B immunity before considering immunosuppressant drugs like infliximab, said Steven J. Czinn, MD, chair of pediatrics at the University of Maryland Medical Center in Baltimore.
"When you make a diagnosis of IBD, you want to treat it aggressively, but it's important to move slowly before starting on biologic therapy, which is exceedingly immunosuppressant," he cautioned.
"Once you start the biologics and suppress the immune system of a patient, it's much more difficult for that patient to develop immunity, so the time to deal with immunizations is at the time of diagnosis."
"The take-home message from these findings is to screen for antibodies and get a good immunization before starting patients on these powerful drugs."
The study did not receive any funding. Dr. Alkhouri and Dr. Czinn have disclosed no relevant financial relationships.
American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Abstract 2. Presented October 18, 2010.
October 21, 2010 (San Antonio, Texas) — Children with inflammatory bowel disease (IBD) who have been vaccinated against hepatitis B virus (HBV) still might not carry adequate antibodies to protect them from infection. This appears to be due to biologic therapy for IBD, according to research presented here at the American College of Gastroenterology 2010 Annual Scientific Meeting and Postgraduate Course.
Biologic drugs, such as infliximab, although considered revolutionary in their ability to treat IBD, are potent immunosuppressants and can reactivate hepatitis B in chronic carriers of the disease. Now it appears that they can also block the effectiveness of HBV immunization.
An evaluation of 100 children who were being treated with infliximab for IBD, including 61 who had received an HBV vaccination, indicated that as many as 33 (54%) of the vaccinated children did not have adequate HBV immunity, defined as 10 mIU/mL or more of antibodies to the hepatitis B surface antigen (anti-HBs).
"First, we showed that no one was a chronic carrier, so that was good, but about half of the children who had been vaccinated for hepatitis B did not have adequate immunity against the disease," said Naim Alkhouri, MD, a coauthor on the study and a gastroenterology fellow at The Cleveland Clinic in Ohio.
"That's very concerning because these patients were on immunosuppressant therapy, and therefore could be at a higher risk for reactivation if they had been chronic carriers, or could be at a greater risk for complications and becoming acutely infected."
The mean age of patients in the study was 17.8 years, and none were positive for the surface antigen of HBV or the antihepatitis B core antigen. The mean concentration of anti-HBs in immune patients was 295.6 ± 350.6 mIU/mL.
The presence of pancolitis and lower albumin levels due to IBD were associated with greater loss of hepatitis B immunity; for each 0.5 g/dL decrease in albumin levels, the likelihood of losing immunity was increased by 62%.
The concurrent use of infliximab, however, did not affect immunity levels, nor did dose or duration. Immunity appears to have been established prior to the initiation of immunosuppressant therapy in the children who exhibited HBV immunity.
"We initially thought that if you were on a higher dose or were taking the drugs more frequently, it could affect your immunity, but we found that that was not the case," said Dr. Alkhouri.
Dr. Alkhouri and his team are now looking into the effect of vaccinating patients with boosters when they are already taking immunosuppressants.
"There is evidence that you do not respond the same way if you are immunosuppressed, so our next step will be to determine the effects of vaccination while on infliximab."
The findings underscore that need to check IBD patients' hepatitis B immunity before considering immunosuppressant drugs like infliximab, said Steven J. Czinn, MD, chair of pediatrics at the University of Maryland Medical Center in Baltimore.
"When you make a diagnosis of IBD, you want to treat it aggressively, but it's important to move slowly before starting on biologic therapy, which is exceedingly immunosuppressant," he cautioned.
"Once you start the biologics and suppress the immune system of a patient, it's much more difficult for that patient to develop immunity, so the time to deal with immunizations is at the time of diagnosis."
"The take-home message from these findings is to screen for antibodies and get a good immunization before starting patients on these powerful drugs."
The study did not receive any funding. Dr. Alkhouri and Dr. Czinn have disclosed no relevant financial relationships.
American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Abstract 2. Presented October 18, 2010.
