Kinrix offers safe, effective immune response with one less dose

Some differences were noted in combination vaccine, including grade-3 pains.

Issue: August 2008

ATLANTA – The newly licensed diphtheria and tetanus toxoids and acellular pertussis vaccine combined with the poliovirus vaccine inactivated delivers an immune response comparable with DTaP vaccine coadministered with IPV with one less injection. It has been added to the Advisory Committee on Immunization Practices’ routine childhood immunization schedule.

Data on the newly licensed vaccine (Kinrix, GlaxoSmithKline) were presented at the Advisory Committee on Immunization Practices meeting in June.

“To complete the recommended childhood immunization schedule in the United States, about 50 doses of vaccine are needed to vaccinate a child from birth to age 18 years. During some office or clinic visits, the administration of up to five separate injections can be indicated,” Greg Wallace, MD, MPH, of the CDC’s National Immunization Program, told Infectious Diseases in Children. “The use of combination vaccines is a practical way to overcome the constraints of multiple injections, especially for starting the immunization series for children behind schedule.”

The combination vaccine first received licensure in France in 1996 and is now available in 33 countries worldwide. The vaccine is indicated for children aged 4 to 6 years as a fifth dose of DTaP (Infanrix, GlaxoSmithKline) and as a fourth dose of invasive pneumococcal disease vaccine (IPOL, GlaxoSmithKline).

“By reducing the number of injections needed by multiple vaccinations, combination vaccines have been associated with improvement in vaccine coverage and vaccine delivery timeliness,” Leonard Friedland, MD, executive director, head of clinical and medical affairs at GlaxoSmithKline Biologicals, said during the meeting.

Supporting licensure

According to Friedland, the bulk of data were derived from a phase-3 pivotal study including more than 4,000 U.S. children; 3,156 of these children received the combination vaccine.

Primary objectives were to assess the safety and immunogenicity as well as lot consistency of the vaccine.

“Following vaccination with the combination vaccine, results indicated geometric mean concentrations increased many fold, and recourses of substance antibody values exceeded cutoffs approaching 100%,” Friedland said. “A high percentage of children with booster responses to diphtheria and tetanus were also found.”

In respect to the three poliovirus antigens, the upper limit of the 95% CI for each ratio was less than the predefined limit of 1.5. Therefore, the researchers were able to conclude noninferiority of the combination vaccine to the invasive pneumococcal disease vaccine regarding the immunogenicity of the vaccine’s poliovirus components.

“Other potential advantages of the combination vaccine include reducing the cost of stocking and administering separate vaccines, reducing the cost for extra health care visits and facilitating the addition of new vaccines into immunization programs,” Wallace said. “The price of a new combination vaccine can sometimes exceed the total price of separate vaccines for the same diseases, however the combination vaccine may represent a better economic value if one considers the direct and indirect costs of extra injections, delayed or missed vaccinations and additional handling and storage.”

Pain, redness, swelling and an increased arm circumference occurring within four days following vaccination were recorded; 57% of children in the combination vaccine group reported injection site pain compared with 53% of children in the DTaP vaccine and invasive pneumococcal disease vaccine group.

“A significant difference was also found for grade-3 pains, with 1.6% of children in the combination group reporting grade-3 pains vs. 0.6% in the DTaP vaccine and invasive pneumococcal disease vaccine group,” Friedland said.

Furthermore, a statistically significant difference was found for fever. Temperature grades in the combination vaccine group reached 38ºC. No fevers greater than 38.5ºC occurred in either group.

Safety

Angela Calugar, MD, MPH, member of the combination vaccines ACIP working group, presented information on the major topics concerning the new DTaP-IPV combination vaccine at the meeting.

“The ACIP-combined working group reviewed the safety and immunogenicity of the combination vaccine and its components,” Calugar said. “On the basis of these data, the expert opinions of the working group members as well as feedback from our partnered organizations, the working group formulated a summary of indications for use of the new licensed vaccine.”

Based on this information, the working group proposed a notice to readers, which will be published in an upcoming issue of Morbidity and Mortality Weekly Report, according to Calugar. – by Jennifer Southall

For more information:

Friedland L. Combination vaccines: Kinrix.

Calugar A. Kinrix safety, immunogenicity, indications and use.

Both presented at: ACIP meeting; June 25-26, 2008; Atlanta.