No Increased Risk of Intussusception After Rotavirus Vaccination

Abstract

Source: Shui IM, Baggs J, Patel M, et al. Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants. JAMA. 2012; 307(6): 598– 604; doi: 10.1001/jama.2012.97In a collaboration between the US Centers for Disease Control and Prevention (CDC) and 8 managed care organizations (the Vaccine Safety Datalink [VSD]), investigators from multiple sites evaluated the risk of intussusception following administration of pentavalent rotavirus (RV5) vaccine to infants aged 4 to 34 weeks between 2006 and 2010. Rates of intussusception among RV5 recipients were compared to those of control infants who received age-appropriate recommended vaccines other than RV5 as well as to background rates among historical control infants from 2001 to 2005 (prior to licensure of RV5). Data on infants who received RV5 outside the recommended age guidelines were excluded. An intussusception episode was identified using International Classification of Diseases, Ninth Revision (ICD-9) codes from hospital, emergency department, and outpatient visits, and then validated through medical record review. Investigators focused on 2 time periods after each RV5 dose, or other vaccine doses in controls, to examine intussusception risk: days 1–7 and days 1–30 after immunization.During the study period, 309,844 first RV5 doses, 257,915 second doses, and 218,966 third doses were administered (total 786,725 doses). There were 389,026 total non-RV5 vaccine doses administered to infants in the control group during the same period. A total of 56 cases of intussusception were identified using ICD-9 codes during the study period in the 30 days following either an RV5 dose (n=30) or a comparison vaccine dose in control infants (n=26). Among the 22 confirmed cases of intussusception, 14 occurred in infants who received RV5 and 8 occurred in the comparison group (relative risk, 0.95; 95% CI, 0.37–2.63). Analysis by dose number (first, second, or third) and time after dose (1–7 or 1–30 days) revealed no significant differences between infants in the RV5 group and those in the comparison group.Compared to historical background rates established from 2001 to 2005, there were no significant increases in the expected rate of intussusception following any RV5 dose for 1–7 or 1–30 day risk windows.The authors conclude that there is no evidence of increased risk of intussusception in US infants receiving RV5 at the recommended ages.Dr Tolan has disclosed no financial relationship relevant to this commentary. Dr Tolan is on the Speaker’s Bureau for Novartis. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The first rotavirus vaccine was removed from the US market when an increased risk of intussusception, particularly in the first week after receipt of the first dose, was recognized during post-licensure monitoring. Subsequently, RV5 and a monovalent rotavirus vaccine were approved for use based upon pre-licensure evaluations of approximately 70,0001 and 60,0002 infants, respectively. Furthermore, an early post-licensure VSD evaluation following approximately 200,000 RV5 doses demonstrated no increased risk of intussusception.3 However, 2 recent international studies demonstrated an increased risk in their populations (Australia4 and Mexico5), raising concern that such a risk might, in fact, exist.With the inclusion of the additional 780,000 doses in this study, the total number of doses now included in US pre- and post-licensure rotavirus RV5 evaluations stands at more than 1 million. These evaluations have detected no evidence of an increased intussusception risk. One of the limitations of the current study is that it only evaluated RV5 doses given to infants with health insurance from one of the participating managed care organizations. It is conceivable that the evidence thus generated may not be generalizable to all US infants. Socioeconomic and demographic differences may help to explain the increased rate of intussusception observed in Mexico, for example.5 Additionally, only those doses given in the recommended time frames were analyzed, and therefore risk of intussusception following late doses cannot be addressed by this study. In the VSD population, 6.5% of first doses were given late.A predominant cause of intussusception is likely wild-type rotavirus infection. Perhaps the background rate will fall as uptake of rotavirus vaccine increases. As we wait for evidence of this, current data are nonetheless overwhelming that RV5 does not increase the risk of intussusception.This is good news. It is hard to ignore the fact that rotavirus vaccination prevented 42,000 to 62,000 infant hospitalizations in 2008.6 The public health impact of this decrease is enormous. The results of this study reinforce that the risk:benefit ratio of rotavirus vaccination is unequivocally positive.