Miriam E. Tucker

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). The onset interval was 2–33 days following immunization. Of the 19 cases, 17 involved patients aged 11–19 years old. Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, said Dr. Davis, director of the CDC's Immunization Safety Office.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11− to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected.

With use of two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively.

If these data accurately represent the true magnitude of increased risk following MCV4 vaccination, then there would be an excess of just 0.89 cases per every million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11− to 14-year-olds vs. 15− to 19-year-olds: For the younger group, the observed versus expected ratio is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15− to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season. Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11− to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15− to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution. Substantial uncertainty exists regarding the risk estimate, using the HCUP or the VSD background incidence rate,” he said.

However, he added, “the timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern.”

A larger study led by Harvard Pilgrim is expected to yield additional data regarding the risk for GBS following MCV4 in approximately 2 years.

Ongoing evaluation of GBS after MCV4 vaccination is also being performed within VSD, Dr. Davis said.

All cases of Guillain-Barré syndrome in a patient following receipt of Menactra should be reported to VAERS, online at http://vaers.hhs.gov

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). The onset interval was 2–33 days following immunization. Of the 19 cases, 17 involved patients aged 11–19 years old. Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, said Dr. Davis, director of the CDC's Immunization Safety Office.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11− to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected.

With use of two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively.

If these data accurately represent the true magnitude of increased risk following MCV4 vaccination, then there would be an excess of just 0.89 cases per every million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11− to 14-year-olds vs. 15− to 19-year-olds: For the younger group, the observed versus expected ratio is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15− to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season. Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11− to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15− to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution. Substantial uncertainty exists regarding the risk estimate, using the HCUP or the VSD background incidence rate,” he said.

However, he added, “the timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern.”

A larger study led by Harvard Pilgrim is expected to yield additional data regarding the risk for GBS following MCV4 in approximately 2 years.

Ongoing evaluation of GBS after MCV4 vaccination is also being performed within VSD, Dr. Davis said.

All cases of Guillain-Barré syndrome in a patient following receipt of Menactra should be reported to VAERS, online at http://vaers.hhs.gov

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). The onset interval was 2–33 days following immunization. Of the 19 cases, 17 involved patients aged 11–19 years old. Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, said Dr. Davis, director of the CDC's Immunization Safety Office.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11− to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected.

With use of two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively.

If these data accurately represent the true magnitude of increased risk following MCV4 vaccination, then there would be an excess of just 0.89 cases per every million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11− to 14-year-olds vs. 15− to 19-year-olds: For the younger group, the observed versus expected ratio is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15− to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season. Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11− to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15− to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution. Substantial uncertainty exists regarding the risk estimate, using the HCUP or the VSD background incidence rate,” he said.

However, he added, “the timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern.”

A larger study led by Harvard Pilgrim is expected to yield additional data regarding the risk for GBS following MCV4 in approximately 2 years.

Ongoing evaluation of GBS after MCV4 vaccination is also being performed within VSD, Dr. Davis said.

All cases of Guillain-Barré syndrome in a patient following receipt of Menactra should be reported to VAERS, online at http://vaers.hhs.gov

WASHINGTON — Autologous platelet concentrate may be helpful in treating difficult-to-heal wounds resulting from Mohs surgery, Dr. Dafnis C. Carranza said at the annual meeting of the American Academy of Dermatology.

Developed in the 1970s, autologous platelet concentrate is a by-product of platelet-rich plasma sequestration containing three to five times the native concentration of platelets. The technique is approved for management of chronic venous stasis wounds and has been used off label for a variety of acute wounds, including those resulting from dental, orthopedic, and plastic surgery.

With Mohs surgery defects, Dr. Carranza and her associates at the University of California, Los Angeles, have seen an average 50% decrease in wound size after one application of autologous platelet concentrate and complete healing after two applications.

"For a biological dressing to be effective, it must be safe and nontoxic to tissue, readily available and inexpensive, accelerate healing, and minimize wound care. We believe an autologous platelet concentrate dressing meets these criteria," said Dr. Carranza, who said that she has "no relevant relationships with industry."

At least two companies, Harvest Technologies and Cytomedix, make autologous platelet concentrate kits. The process involves several steps: First, 20 mL of blood is collected into a syringe containing a citrate-based anticoagulant. The blood is then centrifuged into platelet-rich and platelet-poor plasma and the platelet-poor plasma is discarded, leaving about 3 mL of platelet-rich plasma (PRP).

Next, using a 20G dual-cannula applicator tip, the PRP is combined with thrombin in 10% calcium chloride solution to activate it. The resulting flexible-tissue graft is then contoured to the debrided wound bed. Promogran is then applied over the graft site, followed by Adaptic and XCell cellulose antimicrobial dressing.

The limb is wrapped with sterile gauze roll, secured with Coban, and left in place for 4 days. The patient is seen every 3–4 days for wound cleansing and dressing changes. If the wound is healing well, another PRP application is applied at 2 weeks.

The anecdotal experience of Dr. Carranza and her colleagues suggests that the technique may speed healing of granulating defects of the lower extremities following Mohs micrographic surgery, particularly when healing by secondary intention is unsuccessful.

In one case, an 84-year-old man with multiple comorbidities had undergone Mohs surgery for basal cell carcinoma on the left pretibial area. At 2 months, the defect had excessive granulation tissue and was not healing. Autologous platelets were applied and 1 week later the wound size had decreased by 50%. By 2 weeks it was reduced by 75%. A second application of platelets was given at that time, and by week 3 the wound was healed.

This wound is shown before treatment with platelets.

Healing is evident 3 weeks after treatment with platelets was begun. Photos courtesy Dr. Dafnis C. Carranza

WASHINGTON — Autologous platelet concentrate may be helpful in treating difficult-to-heal wounds resulting from Mohs surgery, Dr. Dafnis C. Carranza said at the annual meeting of the American Academy of Dermatology.

Developed in the 1970s, autologous platelet concentrate is a by-product of platelet-rich plasma sequestration containing three to five times the native concentration of platelets. The technique is approved for management of chronic venous stasis wounds and has been used off label for a variety of acute wounds, including those resulting from dental, orthopedic, and plastic surgery.

With Mohs surgery defects, Dr. Carranza and her associates at the University of California, Los Angeles, have seen an average 50% decrease in wound size after one application of autologous platelet concentrate and complete healing after two applications.

"For a biological dressing to be effective, it must be safe and nontoxic to tissue, readily available and inexpensive, accelerate healing, and minimize wound care. We believe an autologous platelet concentrate dressing meets these criteria," said Dr. Carranza, who said that she has "no relevant relationships with industry."

At least two companies, Harvest Technologies and Cytomedix, make autologous platelet concentrate kits. The process involves several steps: First, 20 mL of blood is collected into a syringe containing a citrate-based anticoagulant. The blood is then centrifuged into platelet-rich and platelet-poor plasma and the platelet-poor plasma is discarded, leaving about 3 mL of platelet-rich plasma (PRP).

Next, using a 20G dual-cannula applicator tip, the PRP is combined with thrombin in 10% calcium chloride solution to activate it. The resulting flexible-tissue graft is then contoured to the debrided wound bed. Promogran is then applied over the graft site, followed by Adaptic and XCell cellulose antimicrobial dressing.

The limb is wrapped with sterile gauze roll, secured with Coban, and left in place for 4 days. The patient is seen every 3–4 days for wound cleansing and dressing changes. If the wound is healing well, another PRP application is applied at 2 weeks.

The anecdotal experience of Dr. Carranza and her colleagues suggests that the technique may speed healing of granulating defects of the lower extremities following Mohs micrographic surgery, particularly when healing by secondary intention is unsuccessful.

In one case, an 84-year-old man with multiple comorbidities had undergone Mohs surgery for basal cell carcinoma on the left pretibial area. At 2 months, the defect had excessive granulation tissue and was not healing. Autologous platelets were applied and 1 week later the wound size had decreased by 50%. By 2 weeks it was reduced by 75%. A second application of platelets was given at that time, and by week 3 the wound was healed.

This wound is shown before treatment with platelets.

Healing is evident 3 weeks after treatment with platelets was begun. Photos courtesy Dr. Dafnis C. Carranza

WASHINGTON — Autologous platelet concentrate may be helpful in treating difficult-to-heal wounds resulting from Mohs surgery, Dr. Dafnis C. Carranza said at the annual meeting of the American Academy of Dermatology.

Developed in the 1970s, autologous platelet concentrate is a by-product of platelet-rich plasma sequestration containing three to five times the native concentration of platelets. The technique is approved for management of chronic venous stasis wounds and has been used off label for a variety of acute wounds, including those resulting from dental, orthopedic, and plastic surgery.

With Mohs surgery defects, Dr. Carranza and her associates at the University of California, Los Angeles, have seen an average 50% decrease in wound size after one application of autologous platelet concentrate and complete healing after two applications.

"For a biological dressing to be effective, it must be safe and nontoxic to tissue, readily available and inexpensive, accelerate healing, and minimize wound care. We believe an autologous platelet concentrate dressing meets these criteria," said Dr. Carranza, who said that she has "no relevant relationships with industry."

At least two companies, Harvest Technologies and Cytomedix, make autologous platelet concentrate kits. The process involves several steps: First, 20 mL of blood is collected into a syringe containing a citrate-based anticoagulant. The blood is then centrifuged into platelet-rich and platelet-poor plasma and the platelet-poor plasma is discarded, leaving about 3 mL of platelet-rich plasma (PRP).

Next, using a 20G dual-cannula applicator tip, the PRP is combined with thrombin in 10% calcium chloride solution to activate it. The resulting flexible-tissue graft is then contoured to the debrided wound bed. Promogran is then applied over the graft site, followed by Adaptic and XCell cellulose antimicrobial dressing.

The limb is wrapped with sterile gauze roll, secured with Coban, and left in place for 4 days. The patient is seen every 3–4 days for wound cleansing and dressing changes. If the wound is healing well, another PRP application is applied at 2 weeks.

The anecdotal experience of Dr. Carranza and her colleagues suggests that the technique may speed healing of granulating defects of the lower extremities following Mohs micrographic surgery, particularly when healing by secondary intention is unsuccessful.

In one case, an 84-year-old man with multiple comorbidities had undergone Mohs surgery for basal cell carcinoma on the left pretibial area. At 2 months, the defect had excessive granulation tissue and was not healing. Autologous platelets were applied and 1 week later the wound size had decreased by 50%. By 2 weeks it was reduced by 75%. A second application of platelets was given at that time, and by week 3 the wound was healed.

This wound is shown before treatment with platelets.

Healing is evident 3 weeks after treatment with platelets was begun. Photos courtesy Dr. Dafnis C. Carranza

ATLANTA — Injection site pain is the most frequently reported adverse event following receipt of the quadrivalent human papillomavirus vaccine, Dr. Lauri Markowitz said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Through January 2007, the passive Vaccine Adverse Event Reporting System (VAERS) has received a total of 542 reports associated with Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil), of which 5% were considered serious. No deaths were reported, said Dr. Markowitz of the CDC's National Center for HIV, STD, and TB Prevention.

A total of 2.1 million doses of Merck's HPV vaccine had been distributed through December 2006. The adverse event reporting rate, 25/100,000 doses, is slightly higher than that seen with other vaccines but “not unexpected for a new vaccine,” she noted.

Injection site pain was the most commonly reported adverse event (18%), followed by dizziness (11%), syncope (11%), fever (9%), and nausea (9%). More than 99% occurred in females, reflecting the population for whom the vaccine currently is recommended. Nearly half (47%) of those reporting adverse events were aged 13–18 years, and another 38% were aged 19–26 years. Only 7% were aged 9–12 years, 6% were over 26 years of age, and the rest were less than 9 years.

There were three reported cases of Guillain-Barré syndrome (GBS), two of whom had simultaneously received the meningococcal conjugate vaccine (Menactra) 9 and 13 days earlier. It was not known whether the third GBS case had received other vaccines at the same time. An association between Menactra and GBS has been reported, although it is not yet clear whether the relationship is causal (MMWR 2006;55:1120–4).

Facial palsy was also reported in three cases, all within 1 day of receiving Gardasil. Two of those individuals had received influenza vaccine—one live attenuated and one inactivated—at the same time. The background rate of facial palsy in the general population is 30/100,000 per year.

“We can confidently say that the observed [rate] is much less than expected,” Dr. Markowitz commenteted.

Physicians are encouraged to report all clinically significant adverse events in patients following receipt of vaccines to VAERS, online at www.vaers.hhs.gov

ATLANTA — Injection site pain is the most frequently reported adverse event following receipt of the quadrivalent human papillomavirus vaccine, Dr. Lauri Markowitz said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Through January 2007, the passive Vaccine Adverse Event Reporting System (VAERS) has received a total of 542 reports associated with Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil), of which 5% were considered serious. No deaths were reported, said Dr. Markowitz of the CDC's National Center for HIV, STD, and TB Prevention.

A total of 2.1 million doses of Merck's HPV vaccine had been distributed through December 2006. The adverse event reporting rate, 25/100,000 doses, is slightly higher than that seen with other vaccines but “not unexpected for a new vaccine,” she noted.

Injection site pain was the most commonly reported adverse event (18%), followed by dizziness (11%), syncope (11%), fever (9%), and nausea (9%). More than 99% occurred in females, reflecting the population for whom the vaccine currently is recommended. Nearly half (47%) of those reporting adverse events were aged 13–18 years, and another 38% were aged 19–26 years. Only 7% were aged 9–12 years, 6% were over 26 years of age, and the rest were less than 9 years.

There were three reported cases of Guillain-Barré syndrome (GBS), two of whom had simultaneously received the meningococcal conjugate vaccine (Menactra) 9 and 13 days earlier. It was not known whether the third GBS case had received other vaccines at the same time. An association between Menactra and GBS has been reported, although it is not yet clear whether the relationship is causal (MMWR 2006;55:1120–4).

Facial palsy was also reported in three cases, all within 1 day of receiving Gardasil. Two of those individuals had received influenza vaccine—one live attenuated and one inactivated—at the same time. The background rate of facial palsy in the general population is 30/100,000 per year.

“We can confidently say that the observed [rate] is much less than expected,” Dr. Markowitz commenteted.

Physicians are encouraged to report all clinically significant adverse events in patients following receipt of vaccines to VAERS, online at www.vaers.hhs.gov

ATLANTA — Injection site pain is the most frequently reported adverse event following receipt of the quadrivalent human papillomavirus vaccine, Dr. Lauri Markowitz said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Through January 2007, the passive Vaccine Adverse Event Reporting System (VAERS) has received a total of 542 reports associated with Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil), of which 5% were considered serious. No deaths were reported, said Dr. Markowitz of the CDC's National Center for HIV, STD, and TB Prevention.

A total of 2.1 million doses of Merck's HPV vaccine had been distributed through December 2006. The adverse event reporting rate, 25/100,000 doses, is slightly higher than that seen with other vaccines but “not unexpected for a new vaccine,” she noted.

Injection site pain was the most commonly reported adverse event (18%), followed by dizziness (11%), syncope (11%), fever (9%), and nausea (9%). More than 99% occurred in females, reflecting the population for whom the vaccine currently is recommended. Nearly half (47%) of those reporting adverse events were aged 13–18 years, and another 38% were aged 19–26 years. Only 7% were aged 9–12 years, 6% were over 26 years of age, and the rest were less than 9 years.

There were three reported cases of Guillain-Barré syndrome (GBS), two of whom had simultaneously received the meningococcal conjugate vaccine (Menactra) 9 and 13 days earlier. It was not known whether the third GBS case had received other vaccines at the same time. An association between Menactra and GBS has been reported, although it is not yet clear whether the relationship is causal (MMWR 2006;55:1120–4).

Facial palsy was also reported in three cases, all within 1 day of receiving Gardasil. Two of those individuals had received influenza vaccine—one live attenuated and one inactivated—at the same time. The background rate of facial palsy in the general population is 30/100,000 per year.

“We can confidently say that the observed [rate] is much less than expected,” Dr. Markowitz commenteted.

Physicians are encouraged to report all clinically significant adverse events in patients following receipt of vaccines to VAERS, online at www.vaers.hhs.gov

ATLANTA — The investigational cervical cancer vaccine Cervarix remained 100% effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98.1%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia (CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

The vaccine also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains associated with cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of all cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women over 25 years of age, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections do decrease with age, the risk of persistence actually increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0-, 1-, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women over 25 years of age is also ongoing, while trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

Regulatory files for Cervarix were submitted to the European Union and internationally in 2006. In the United States, the biologic license application is “on target for submission by April 2007,” Dr. Dubin reported.

ATLANTA — The investigational cervical cancer vaccine Cervarix remained 100% effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98.1%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia (CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

The vaccine also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains associated with cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of all cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women over 25 years of age, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections do decrease with age, the risk of persistence actually increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0-, 1-, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women over 25 years of age is also ongoing, while trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

Regulatory files for Cervarix were submitted to the European Union and internationally in 2006. In the United States, the biologic license application is “on target for submission by April 2007,” Dr. Dubin reported.

ATLANTA — The investigational cervical cancer vaccine Cervarix remained 100% effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98.1%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia (CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

The vaccine also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains associated with cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of all cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women over 25 years of age, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections do decrease with age, the risk of persistence actually increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0-, 1-, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women over 25 years of age is also ongoing, while trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

Regulatory files for Cervarix were submitted to the European Union and internationally in 2006. In the United States, the biologic license application is “on target for submission by April 2007,” Dr. Dubin reported.

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). The onset interval was 2–33 days following immunization.

Seventeen of the 19 were aged 11–19 years old.

Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, said Dr. Davis, director of the CDC's Immunization Safety Office.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11- to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected.

With use of two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively. If these data accurately represent the true magnitude of increased risk after MCV4 vaccination, then there would be an excess of just 0.89 cases per million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11- to 14-year-olds vs. 15- to 19-year-olds: For the younger set, the observed vs. expected is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15- to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season.

Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11- to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15- to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution. Substantial uncertainty exists regarding the risk estimate, using the HCUP or the VSD background incidence rate,” he said.

However, he added, “the timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern.”

A larger study led by Harvard Pilgrim is expected to yield additional data regarding the risk for GBS following MCV4 in approximately 2 years.

Ongoing evaluation of GBS after MCV4 vaccination is also being performed within VSD, Dr. Davis said.

All cases of Guillain-Barré syndrome in a patient following receipt of Menactra should be reported to VAERS, online at http://vaers.hhs.gov

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). The onset interval was 2–33 days following immunization.

Seventeen of the 19 were aged 11–19 years old.

Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, said Dr. Davis, director of the CDC's Immunization Safety Office.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11- to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected.

With use of two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively. If these data accurately represent the true magnitude of increased risk after MCV4 vaccination, then there would be an excess of just 0.89 cases per million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11- to 14-year-olds vs. 15- to 19-year-olds: For the younger set, the observed vs. expected is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15- to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season.

Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11- to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15- to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution. Substantial uncertainty exists regarding the risk estimate, using the HCUP or the VSD background incidence rate,” he said.

However, he added, “the timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern.”

A larger study led by Harvard Pilgrim is expected to yield additional data regarding the risk for GBS following MCV4 in approximately 2 years.

Ongoing evaluation of GBS after MCV4 vaccination is also being performed within VSD, Dr. Davis said.

All cases of Guillain-Barré syndrome in a patient following receipt of Menactra should be reported to VAERS, online at http://vaers.hhs.gov

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). The onset interval was 2–33 days following immunization.

Seventeen of the 19 were aged 11–19 years old.

Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, said Dr. Davis, director of the CDC's Immunization Safety Office.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11- to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected.

With use of two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively. If these data accurately represent the true magnitude of increased risk after MCV4 vaccination, then there would be an excess of just 0.89 cases per million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11- to 14-year-olds vs. 15- to 19-year-olds: For the younger set, the observed vs. expected is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15- to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season.

Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11- to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15- to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution. Substantial uncertainty exists regarding the risk estimate, using the HCUP or the VSD background incidence rate,” he said.

However, he added, “the timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern.”

A larger study led by Harvard Pilgrim is expected to yield additional data regarding the risk for GBS following MCV4 in approximately 2 years.

Ongoing evaluation of GBS after MCV4 vaccination is also being performed within VSD, Dr. Davis said.

All cases of Guillain-Barré syndrome in a patient following receipt of Menactra should be reported to VAERS, online at http://vaers.hhs.gov

WASHINGTON — Preliminary data suggest no increased risk for adverse pregnancy outcomes in women exposed to either etanercept or adalimumab during the first trimester, Christina Chambers, Ph.D., reported in two posters at the annual meeting of the American Academy of Dermatology.

Although the numbers are small thus far, no worrisome pattern has emerged. “Based on preliminary data at the present time, we don't see any big red flags,” said Dr. Chambers, a perinatal epidemiologist at the University of California, San Diego, who specializes in drug safety during pregnancy.

The prospective cohort data come from the Organization of Teratology Information Specialists (OTIS), a network of telephone-based teratology counseling services based at hospitals and universities throughout the United States and Canada. Since 1999, network members have collaborated on the OTIS Autoimmune Diseases in Pregnancy Project, a registry study focused on the safety of medications used to treat a variety of autoimmune diseases. The project is sponsored in part by research grants from several pharmaceutical companies, including Amgen Inc., the manufacturer of etanercept (Enbrel), and Abbott Laboratories, maker of adalimumab (Humira).

Both etanercept and adalimumab are self-injectable anti-tumor necrosis factor-α monoclonal antibody medications approved in the United States for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis.

Etanercept is also approved for treating psoriasis and ankylosing spondylitis. Dr. Chambers presented early data from ongoing studies of both drugs.

A total of 82 women were enrolled in the etanercept study between March 2005 and October 2006. Of those, 48 were exposed to etanercept: 28 for RA, 14 for psoriasis or psoriatic arthritis, and 6 for ankylosing spondylitis.

Another 34 women who did not take etanercept were also enrolled: 18 with RA, 14 with psoriasis or psoriatic arthritis, and 2 with ankylosing spondylitis. Mean age was about 33 years in both groups, and mean gestational age at enrollment was 11.4 weeks for the etanercept-exposed group and 12.2 weeks for the disease-matched comparison group.

Outcome was known for 42 pregnancies as of October 2006. No stillbirths occurred in either group. There was one spontaneous abortion among the 22 in the etanercept group (4.5%), far below both the 3 of 20 (15%) in the disease-matched comparison group and the 10%–15% pregnancy loss rate in the general population, Dr. Chambers noted.

Gestational age was 37.5 weeks for the etanercept group, which was not significantly different from the 37.8 weeks for the disease-matched controls.

Gestational age in both groups, however, was about a week earlier than normal, a phenomenon that has been documented previously in patients with RA. Similarly, birth weights—3,323 g for the etanercept group and 3,317 g for the nonexposed disease-matched women—were slightly lower than the 3,400–3,500 g average birth weight in the general population, but were not increased in those with etanercept exposure, she said.

Of the 21 infants born alive in the etanercept group, three had major defects: One infant, a twin, was born with malrotation of the stomach, which required surgery; a preterm infant had a unilateral inguinal hernia that required surgery; and a third, whose mother had Hashimoto's thyroiditis, was born with congenital hypothyroidism.

In the comparison group, one pregnancy was terminated following a prenatal diagnosis of Down syndrome.

The adalimumab data set comprised a total of 130 women who were enrolled in the prospective cohort study: 23 exposed to adalimumab for the treatment of RA, 48 with disease who did not take adalimumab, and 26 without disease.

Another 33 women who did not meet the study cohort criteria were also enrolled in the adalimumab pregnancy registry. These included five women treated for Crohn's disease, two treated for psoriasis or psoriatic arthritis, and two others treated for nonspecific autoimmune disorders.

Rates of spontaneous abortion among the pregnancies with known outcome were higher among all the groups with RA or other autoimmune disease: 2 (11.8%) of the 17 in the adalimumab study cohort, 5 (20.0%) of the 25 from the registry, and 3 (7.1%) of the 42 in the diseased comparison group, versus 0 of 15 pregnancies with known outcomes among healthy women who were not exposed to adalimumab. The only stillbirth occurred in the healthy nonexposed group.

As with etanercept, no increased risks for preterm delivery or malformations were seen with adalimumab exposure. There was one preterm delivery among the 15 live births in the study cohort (7%), compared with 4 of the 14 in the registry (29%), 7 of the 37 in the disease comparison group (19%), and 0 of the 14 in the nondisease comparison group.

Malformations occurred in none of the 17 total known outcomes in the study (0%), in 1 of 14 in the registry (7%), in 1 of 42 disease comparison patients (2%), and in 1 of 15 of the healthy controls (7%).

In both of these drug studies, all of the infants will be evaluated up to 1 year of age for major and minor anomalies by pediatric specialists, Dr. Chambers said.

Final results for preterm delivery, birth weight, and congenital malformations should be available in 1–2 years. In the meantime, even these small preliminary numbers are reassuring because they don't show any particular pattern.

“All the major teratogens are associated with very specific patterns of abnormal outcomes. When you don't see a pattern and you just see one of this and one of that, it makes you a little more confident that this is not an Accutane,” Dr. Chambers said.

Physicians who prescribe etanercept and adalimumab to women of childbearing age are encouraged to enroll patients in OTIS. For more information, call 877-311-8972 or e-mail Dr. Chambers at chchambers@ucsd.edu

WASHINGTON — Preliminary data suggest no increased risk for adverse pregnancy outcomes in women exposed to either etanercept or adalimumab during the first trimester, Christina Chambers, Ph.D., reported in two posters at the annual meeting of the American Academy of Dermatology.

Although the numbers are small thus far, no worrisome pattern has emerged. “Based on preliminary data at the present time, we don't see any big red flags,” said Dr. Chambers, a perinatal epidemiologist at the University of California, San Diego, who specializes in drug safety during pregnancy.

The prospective cohort data come from the Organization of Teratology Information Specialists (OTIS), a network of telephone-based teratology counseling services based at hospitals and universities throughout the United States and Canada. Since 1999, network members have collaborated on the OTIS Autoimmune Diseases in Pregnancy Project, a registry study focused on the safety of medications used to treat a variety of autoimmune diseases. The project is sponsored in part by research grants from several pharmaceutical companies, including Amgen Inc., the manufacturer of etanercept (Enbrel), and Abbott Laboratories, maker of adalimumab (Humira).

Both etanercept and adalimumab are self-injectable anti-tumor necrosis factor-α monoclonal antibody medications approved in the United States for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis.

Etanercept is also approved for treating psoriasis and ankylosing spondylitis. Dr. Chambers presented early data from ongoing studies of both drugs.

A total of 82 women were enrolled in the etanercept study between March 2005 and October 2006. Of those, 48 were exposed to etanercept: 28 for RA, 14 for psoriasis or psoriatic arthritis, and 6 for ankylosing spondylitis.

Another 34 women who did not take etanercept were also enrolled: 18 with RA, 14 with psoriasis or psoriatic arthritis, and 2 with ankylosing spondylitis. Mean age was about 33 years in both groups, and mean gestational age at enrollment was 11.4 weeks for the etanercept-exposed group and 12.2 weeks for the disease-matched comparison group.

Outcome was known for 42 pregnancies as of October 2006. No stillbirths occurred in either group. There was one spontaneous abortion among the 22 in the etanercept group (4.5%), far below both the 3 of 20 (15%) in the disease-matched comparison group and the 10%–15% pregnancy loss rate in the general population, Dr. Chambers noted.

Gestational age was 37.5 weeks for the etanercept group, which was not significantly different from the 37.8 weeks for the disease-matched controls.

Gestational age in both groups, however, was about a week earlier than normal, a phenomenon that has been documented previously in patients with RA. Similarly, birth weights—3,323 g for the etanercept group and 3,317 g for the nonexposed disease-matched women—were slightly lower than the 3,400–3,500 g average birth weight in the general population, but were not increased in those with etanercept exposure, she said.

Of the 21 infants born alive in the etanercept group, three had major defects: One infant, a twin, was born with malrotation of the stomach, which required surgery; a preterm infant had a unilateral inguinal hernia that required surgery; and a third, whose mother had Hashimoto's thyroiditis, was born with congenital hypothyroidism.

In the comparison group, one pregnancy was terminated following a prenatal diagnosis of Down syndrome.

The adalimumab data set comprised a total of 130 women who were enrolled in the prospective cohort study: 23 exposed to adalimumab for the treatment of RA, 48 with disease who did not take adalimumab, and 26 without disease.

Another 33 women who did not meet the study cohort criteria were also enrolled in the adalimumab pregnancy registry. These included five women treated for Crohn's disease, two treated for psoriasis or psoriatic arthritis, and two others treated for nonspecific autoimmune disorders.

Rates of spontaneous abortion among the pregnancies with known outcome were higher among all the groups with RA or other autoimmune disease: 2 (11.8%) of the 17 in the adalimumab study cohort, 5 (20.0%) of the 25 from the registry, and 3 (7.1%) of the 42 in the diseased comparison group, versus 0 of 15 pregnancies with known outcomes among healthy women who were not exposed to adalimumab. The only stillbirth occurred in the healthy nonexposed group.

As with etanercept, no increased risks for preterm delivery or malformations were seen with adalimumab exposure. There was one preterm delivery among the 15 live births in the study cohort (7%), compared with 4 of the 14 in the registry (29%), 7 of the 37 in the disease comparison group (19%), and 0 of the 14 in the nondisease comparison group.

Malformations occurred in none of the 17 total known outcomes in the study (0%), in 1 of 14 in the registry (7%), in 1 of 42 disease comparison patients (2%), and in 1 of 15 of the healthy controls (7%).

In both of these drug studies, all of the infants will be evaluated up to 1 year of age for major and minor anomalies by pediatric specialists, Dr. Chambers said.

Final results for preterm delivery, birth weight, and congenital malformations should be available in 1–2 years. In the meantime, even these small preliminary numbers are reassuring because they don't show any particular pattern.

“All the major teratogens are associated with very specific patterns of abnormal outcomes. When you don't see a pattern and you just see one of this and one of that, it makes you a little more confident that this is not an Accutane,” Dr. Chambers said.

Physicians who prescribe etanercept and adalimumab to women of childbearing age are encouraged to enroll patients in OTIS. For more information, call 877-311-8972 or e-mail Dr. Chambers at chchambers@ucsd.edu

WASHINGTON — Preliminary data suggest no increased risk for adverse pregnancy outcomes in women exposed to either etanercept or adalimumab during the first trimester, Christina Chambers, Ph.D., reported in two posters at the annual meeting of the American Academy of Dermatology.

Although the numbers are small thus far, no worrisome pattern has emerged. “Based on preliminary data at the present time, we don't see any big red flags,” said Dr. Chambers, a perinatal epidemiologist at the University of California, San Diego, who specializes in drug safety during pregnancy.

The prospective cohort data come from the Organization of Teratology Information Specialists (OTIS), a network of telephone-based teratology counseling services based at hospitals and universities throughout the United States and Canada. Since 1999, network members have collaborated on the OTIS Autoimmune Diseases in Pregnancy Project, a registry study focused on the safety of medications used to treat a variety of autoimmune diseases. The project is sponsored in part by research grants from several pharmaceutical companies, including Amgen Inc., the manufacturer of etanercept (Enbrel), and Abbott Laboratories, maker of adalimumab (Humira).

Both etanercept and adalimumab are self-injectable anti-tumor necrosis factor-α monoclonal antibody medications approved in the United States for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis.

Etanercept is also approved for treating psoriasis and ankylosing spondylitis. Dr. Chambers presented early data from ongoing studies of both drugs.

A total of 82 women were enrolled in the etanercept study between March 2005 and October 2006. Of those, 48 were exposed to etanercept: 28 for RA, 14 for psoriasis or psoriatic arthritis, and 6 for ankylosing spondylitis.

Another 34 women who did not take etanercept were also enrolled: 18 with RA, 14 with psoriasis or psoriatic arthritis, and 2 with ankylosing spondylitis. Mean age was about 33 years in both groups, and mean gestational age at enrollment was 11.4 weeks for the etanercept-exposed group and 12.2 weeks for the disease-matched comparison group.

Outcome was known for 42 pregnancies as of October 2006. No stillbirths occurred in either group. There was one spontaneous abortion among the 22 in the etanercept group (4.5%), far below both the 3 of 20 (15%) in the disease-matched comparison group and the 10%–15% pregnancy loss rate in the general population, Dr. Chambers noted.

Gestational age was 37.5 weeks for the etanercept group, which was not significantly different from the 37.8 weeks for the disease-matched controls.

Gestational age in both groups, however, was about a week earlier than normal, a phenomenon that has been documented previously in patients with RA. Similarly, birth weights—3,323 g for the etanercept group and 3,317 g for the nonexposed disease-matched women—were slightly lower than the 3,400–3,500 g average birth weight in the general population, but were not increased in those with etanercept exposure, she said.

Of the 21 infants born alive in the etanercept group, three had major defects: One infant, a twin, was born with malrotation of the stomach, which required surgery; a preterm infant had a unilateral inguinal hernia that required surgery; and a third, whose mother had Hashimoto's thyroiditis, was born with congenital hypothyroidism.

In the comparison group, one pregnancy was terminated following a prenatal diagnosis of Down syndrome.

The adalimumab data set comprised a total of 130 women who were enrolled in the prospective cohort study: 23 exposed to adalimumab for the treatment of RA, 48 with disease who did not take adalimumab, and 26 without disease.

Another 33 women who did not meet the study cohort criteria were also enrolled in the adalimumab pregnancy registry. These included five women treated for Crohn's disease, two treated for psoriasis or psoriatic arthritis, and two others treated for nonspecific autoimmune disorders.

Rates of spontaneous abortion among the pregnancies with known outcome were higher among all the groups with RA or other autoimmune disease: 2 (11.8%) of the 17 in the adalimumab study cohort, 5 (20.0%) of the 25 from the registry, and 3 (7.1%) of the 42 in the diseased comparison group, versus 0 of 15 pregnancies with known outcomes among healthy women who were not exposed to adalimumab. The only stillbirth occurred in the healthy nonexposed group.

As with etanercept, no increased risks for preterm delivery or malformations were seen with adalimumab exposure. There was one preterm delivery among the 15 live births in the study cohort (7%), compared with 4 of the 14 in the registry (29%), 7 of the 37 in the disease comparison group (19%), and 0 of the 14 in the nondisease comparison group.

Malformations occurred in none of the 17 total known outcomes in the study (0%), in 1 of 14 in the registry (7%), in 1 of 42 disease comparison patients (2%), and in 1 of 15 of the healthy controls (7%).

In both of these drug studies, all of the infants will be evaluated up to 1 year of age for major and minor anomalies by pediatric specialists, Dr. Chambers said.

Final results for preterm delivery, birth weight, and congenital malformations should be available in 1–2 years. In the meantime, even these small preliminary numbers are reassuring because they don't show any particular pattern.

“All the major teratogens are associated with very specific patterns of abnormal outcomes. When you don't see a pattern and you just see one of this and one of that, it makes you a little more confident that this is not an Accutane,” Dr. Chambers said.

Physicians who prescribe etanercept and adalimumab to women of childbearing age are encouraged to enroll patients in OTIS. For more information, call 877-311-8972 or e-mail Dr. Chambers at chchambers@ucsd.edu

WASHINGTON — Patients with active rheumatoid arthritis preferred the adalimumab autoinjection pen device to the prefilled syringe in an Abbott-sponsored study, Dr. Martin Okun reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

Adalimumab, a fully human IgG monoclonal anti-tumor necrosis factor, is approved for the treatment of adults with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. It can be administered via subcutaneous injection with a prefilled syringe or by an autoinjection pen, which was developed to facilitate self-injection by patients with physically limiting autoimmune diseases, noted Dr. Okun of Abbott Laboratory's department of medical affairs.

The investigators evaluated existing data from an earlier open-label phase II study that was done in pursuit of the original Food and Drug Administration approval of 52 patients with active RA who self-administered 40 mg adalimumab subcutaneously with the syringe at visit 1, followed by the same dose via the pen at visits 2 (at week 2) and 3 (week 4). The patients chose the site—either thigh or abdomen—and maintained the same site for all three injections.

The patients had a mean age of 54 years and a mean RA duration of 8 years. Two-thirds were women, and the majority (88.5%) were white. They had been injecting adalimumab via syringe for a mean of 15 months.

On the 10-point visual analog scale, with 0 being “no pain” and 10 being “as bad as it could be,” the patients rated their pain immediately following injection as a mean of 3.7 with the syringe at visit 1, compared with 2.3 and 2.0, respectively, for the pen at visits 2 and 3.

Overall, 40 patients (77%) deemed the pen to be less painful than the syringe, while 4 patients (8%) found the syringe less painful and 8 (15%) had no preference. Significant reductions in injection-site pain were observed at 15–30 minutes post injection with the pen, Dr. Okun reported.

Overall impressions of the injection experience with the pen were rated “favorable” or “extremely favorable” by 86.5% at visit 2 and 88.5% at visit 3, compared with just 32.6% for the syringe at visit 1. Overall preference was 88.5% for the pen compared with 5.8% for the syringe and 5.8% with no preference.

Reasons listed for preferring the pen included ease of use, convenience, time to inject (about 10 seconds versus 30 seconds for the syringe), safety, and “less pain.” More than 94% of the patients said they would likely use the pen if it were available at the same cost as the syringe, and the same proportion said they would recommend the pen to another patient, Dr. Okun reported.

Poster session moderator Dr. Craig Leonardi, a dermatologist at St. Louis University, cautioned that patients must be trained to use the pen. “It's not sufficient to just prescribe the pen. You have to show patients how to use it. Otherwise they make mistakes.”

WASHINGTON — Patients with active rheumatoid arthritis preferred the adalimumab autoinjection pen device to the prefilled syringe in an Abbott-sponsored study, Dr. Martin Okun reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

Adalimumab, a fully human IgG monoclonal anti-tumor necrosis factor, is approved for the treatment of adults with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. It can be administered via subcutaneous injection with a prefilled syringe or by an autoinjection pen, which was developed to facilitate self-injection by patients with physically limiting autoimmune diseases, noted Dr. Okun of Abbott Laboratory's department of medical affairs.

The investigators evaluated existing data from an earlier open-label phase II study that was done in pursuit of the original Food and Drug Administration approval of 52 patients with active RA who self-administered 40 mg adalimumab subcutaneously with the syringe at visit 1, followed by the same dose via the pen at visits 2 (at week 2) and 3 (week 4). The patients chose the site—either thigh or abdomen—and maintained the same site for all three injections.

The patients had a mean age of 54 years and a mean RA duration of 8 years. Two-thirds were women, and the majority (88.5%) were white. They had been injecting adalimumab via syringe for a mean of 15 months.

On the 10-point visual analog scale, with 0 being “no pain” and 10 being “as bad as it could be,” the patients rated their pain immediately following injection as a mean of 3.7 with the syringe at visit 1, compared with 2.3 and 2.0, respectively, for the pen at visits 2 and 3.

Overall, 40 patients (77%) deemed the pen to be less painful than the syringe, while 4 patients (8%) found the syringe less painful and 8 (15%) had no preference. Significant reductions in injection-site pain were observed at 15–30 minutes post injection with the pen, Dr. Okun reported.

Overall impressions of the injection experience with the pen were rated “favorable” or “extremely favorable” by 86.5% at visit 2 and 88.5% at visit 3, compared with just 32.6% for the syringe at visit 1. Overall preference was 88.5% for the pen compared with 5.8% for the syringe and 5.8% with no preference.

Reasons listed for preferring the pen included ease of use, convenience, time to inject (about 10 seconds versus 30 seconds for the syringe), safety, and “less pain.” More than 94% of the patients said they would likely use the pen if it were available at the same cost as the syringe, and the same proportion said they would recommend the pen to another patient, Dr. Okun reported.

Poster session moderator Dr. Craig Leonardi, a dermatologist at St. Louis University, cautioned that patients must be trained to use the pen. “It's not sufficient to just prescribe the pen. You have to show patients how to use it. Otherwise they make mistakes.”

WASHINGTON — Patients with active rheumatoid arthritis preferred the adalimumab autoinjection pen device to the prefilled syringe in an Abbott-sponsored study, Dr. Martin Okun reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

Adalimumab, a fully human IgG monoclonal anti-tumor necrosis factor, is approved for the treatment of adults with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. It can be administered via subcutaneous injection with a prefilled syringe or by an autoinjection pen, which was developed to facilitate self-injection by patients with physically limiting autoimmune diseases, noted Dr. Okun of Abbott Laboratory's department of medical affairs.

The investigators evaluated existing data from an earlier open-label phase II study that was done in pursuit of the original Food and Drug Administration approval of 52 patients with active RA who self-administered 40 mg adalimumab subcutaneously with the syringe at visit 1, followed by the same dose via the pen at visits 2 (at week 2) and 3 (week 4). The patients chose the site—either thigh or abdomen—and maintained the same site for all three injections.

The patients had a mean age of 54 years and a mean RA duration of 8 years. Two-thirds were women, and the majority (88.5%) were white. They had been injecting adalimumab via syringe for a mean of 15 months.

On the 10-point visual analog scale, with 0 being “no pain” and 10 being “as bad as it could be,” the patients rated their pain immediately following injection as a mean of 3.7 with the syringe at visit 1, compared with 2.3 and 2.0, respectively, for the pen at visits 2 and 3.

Overall, 40 patients (77%) deemed the pen to be less painful than the syringe, while 4 patients (8%) found the syringe less painful and 8 (15%) had no preference. Significant reductions in injection-site pain were observed at 15–30 minutes post injection with the pen, Dr. Okun reported.

Overall impressions of the injection experience with the pen were rated “favorable” or “extremely favorable” by 86.5% at visit 2 and 88.5% at visit 3, compared with just 32.6% for the syringe at visit 1. Overall preference was 88.5% for the pen compared with 5.8% for the syringe and 5.8% with no preference.

Reasons listed for preferring the pen included ease of use, convenience, time to inject (about 10 seconds versus 30 seconds for the syringe), safety, and “less pain.” More than 94% of the patients said they would likely use the pen if it were available at the same cost as the syringe, and the same proportion said they would recommend the pen to another patient, Dr. Okun reported.

Poster session moderator Dr. Craig Leonardi, a dermatologist at St. Louis University, cautioned that patients must be trained to use the pen. “It's not sufficient to just prescribe the pen. You have to show patients how to use it. Otherwise they make mistakes.”

ATLANTA — Recent efforts to broaden influenza immunization among children have kept the thimerosal/autism issue on the front burner for the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The link was evident at the ACIP's winter meeting, where plans were discussed to expand the recommended age range to receive annual flu shots from the current 6 months-5 years to children up through age 18. This could happen as soon as the 2008–2009 influenza season (see story above).

Most routine childhood vaccines no longer contain thimerosal, but influenza vaccine remains a notable exception: Only the intranasal vaccine and one brand of injectable influenza vaccine are currently thimerosal free, while the rest still contain small amounts. All of the influenza vaccine manufacturers are working toward producing preservative-free vaccine, and greater capacity is expected over the next 3–5 years, Dr. Anthony Fiore of the CDC's National Center for Influenza and Respiratory Diseases told the committee.

In the meantime, activist groups claiming a link between thimerosal and the documented rise in the number of children being diagnosed with autism spectrum disorders have kept the issue in the news and on the ACIP's agenda. The committee's 2007–2008 influenza statement will specifically state that “no scientifically conclusive evidence has demonstrated harm from exposure to thimerosal preservative-containing vaccine” and that individuals receiving influenza vaccine may be given “any age- and risk-factor appropriate vaccine preparation, depending on availability.”

At the committee's request, Dr. Jay M. Lieberman presented a summary of the evidence regarding autism and thimerosal, an organic preservative containing 50% ethylmercury that once was commonly used in multidose vaccine containers to prevent microbial growth.

In 1999, the American Academy of Pediatrics and the U.S. Food and Drug Administration urged manufacturers to remove thimerosal from vaccines as quickly as possible, because of the discovery that young children receiving multiple immunizations could exceed the total mercury exposure level recommended by the Environmental Protection Agency, said Dr. Lieberman, chief of pediatric infectious diseases at Miller Children's Hospital, Long Beach, Calif.

In a subsequent statement, the CDC noted that the goal of removing thimerosal from vaccines was “established as a precautionary measure to maintain the public's trust in immunization,” and that “there was no evidence of any harm caused by the low levels in vaccines, but removal would make vaccines safer” (MMWR 2000;49:622).

The relevant data come primarily from cohort and ecological studies. In a population-based cohort study of all 467,450 children born in Denmark during 1990–1996, the risk of autism and autism spectrum disorders did not differ significantly between those vaccinated with thimerosal-containing vaccines and those who received the thimerosal-free versions, and there was no evidence for a dose-response association (JAMA 2003;290:1763–6).

Preliminary data from a 1999 “screening study” of more than 140,000 U.S. children in the Vaccine Safety Datalink Project did suggest an association between thimerosal exposure and “any neurodevelopmental disorder”—but not autism—at 3 months. Those initial results have been widely quoted by activists as evidence for the dangers of thimerosal. However, the study showed no clear association between infant exposure to thimerosal and specific neurodevelopmental disorders. After various methodological errors and issues were resolved, the final published version of the report was less conclusive (Pediatrics 2003;11:1039–48).

“It's important to note that this study was undertaken to identify outcomes that warranted additional study. The authors recognized that there were likely to be other important factors that couldn't be addressed in this study design,” Dr. Lieberman said.

While the increase in the incidence and prevalence of autism spectrum disorders in the United States during the 1980s and 1990s paralleled exposure to thimerosal-containing vaccines, the story is different in Denmark and Sweden, where rates of autism continued to rise even after thimerosal was removed from vaccines (Am. J. Prev. Med. 2003;25:101–6 and Pediatrics 2003;112:604–6). Similarly, emerging data in the United States suggest that autism rates have not decreased with the removal of thimerosal from routine childhood vaccines, Dr. Lieberman noted.

In 2004, a data review by the Institute of Medicine determined that “the evidence favors rejection of a causal relationship” between thimerosal-containing vaccines and autism.

But judging by some of the public comments at the meeting, not everyone is convinced. Lyn Redwood, R.N., president and cofounder of a nonprofit organization called Sensible Action for Ending Mercury-Induced Neurological Disorders (SafeMinds), urged the ACIP to stop recommending any vaccines that contain thimerosal. She read a list of titles from published scientific articles, such as “Thimerosal Neurotoxicity Is Associated With Glutathione Depletion: Protection With Glutathione Precursors” (Neurotoxicology 2005;26:1–8).

“I just don't see how the committee can avoid these types of studies and cherry-pick the data,” said Ms. Redwood, who has a son diagnosed with pervasive developmental disorder.

More data from the Vaccine Safety Datalink Project are due out soon. This time, the CDC will look at children born from 1994 through 1999—the period when thimerosal-containing vaccines were used frequently. Prenatal and postnatal mercury exposure up to 7 months of age will be quantified, and a variety of assessments for autism and various measures of cognition will be performed.

Dr. Lieberman has financial relationships with Merck & Co., MedImmune, GlaxoSmithKline, and Sanofi Pasteur.

ATLANTA — Recent efforts to broaden influenza immunization among children have kept the thimerosal/autism issue on the front burner for the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The link was evident at the ACIP's winter meeting, where plans were discussed to expand the recommended age range to receive annual flu shots from the current 6 months-5 years to children up through age 18. This could happen as soon as the 2008–2009 influenza season (see story above).

Most routine childhood vaccines no longer contain thimerosal, but influenza vaccine remains a notable exception: Only the intranasal vaccine and one brand of injectable influenza vaccine are currently thimerosal free, while the rest still contain small amounts. All of the influenza vaccine manufacturers are working toward producing preservative-free vaccine, and greater capacity is expected over the next 3–5 years, Dr. Anthony Fiore of the CDC's National Center for Influenza and Respiratory Diseases told the committee.

In the meantime, activist groups claiming a link between thimerosal and the documented rise in the number of children being diagnosed with autism spectrum disorders have kept the issue in the news and on the ACIP's agenda. The committee's 2007–2008 influenza statement will specifically state that “no scientifically conclusive evidence has demonstrated harm from exposure to thimerosal preservative-containing vaccine” and that individuals receiving influenza vaccine may be given “any age- and risk-factor appropriate vaccine preparation, depending on availability.”

At the committee's request, Dr. Jay M. Lieberman presented a summary of the evidence regarding autism and thimerosal, an organic preservative containing 50% ethylmercury that once was commonly used in multidose vaccine containers to prevent microbial growth.

In 1999, the American Academy of Pediatrics and the U.S. Food and Drug Administration urged manufacturers to remove thimerosal from vaccines as quickly as possible, because of the discovery that young children receiving multiple immunizations could exceed the total mercury exposure level recommended by the Environmental Protection Agency, said Dr. Lieberman, chief of pediatric infectious diseases at Miller Children's Hospital, Long Beach, Calif.

In a subsequent statement, the CDC noted that the goal of removing thimerosal from vaccines was “established as a precautionary measure to maintain the public's trust in immunization,” and that “there was no evidence of any harm caused by the low levels in vaccines, but removal would make vaccines safer” (MMWR 2000;49:622).

The relevant data come primarily from cohort and ecological studies. In a population-based cohort study of all 467,450 children born in Denmark during 1990–1996, the risk of autism and autism spectrum disorders did not differ significantly between those vaccinated with thimerosal-containing vaccines and those who received the thimerosal-free versions, and there was no evidence for a dose-response association (JAMA 2003;290:1763–6).

Preliminary data from a 1999 “screening study” of more than 140,000 U.S. children in the Vaccine Safety Datalink Project did suggest an association between thimerosal exposure and “any neurodevelopmental disorder”—but not autism—at 3 months. Those initial results have been widely quoted by activists as evidence for the dangers of thimerosal. However, the study showed no clear association between infant exposure to thimerosal and specific neurodevelopmental disorders. After various methodological errors and issues were resolved, the final published version of the report was less conclusive (Pediatrics 2003;11:1039–48).

“It's important to note that this study was undertaken to identify outcomes that warranted additional study. The authors recognized that there were likely to be other important factors that couldn't be addressed in this study design,” Dr. Lieberman said.

While the increase in the incidence and prevalence of autism spectrum disorders in the United States during the 1980s and 1990s paralleled exposure to thimerosal-containing vaccines, the story is different in Denmark and Sweden, where rates of autism continued to rise even after thimerosal was removed from vaccines (Am. J. Prev. Med. 2003;25:101–6 and Pediatrics 2003;112:604–6). Similarly, emerging data in the United States suggest that autism rates have not decreased with the removal of thimerosal from routine childhood vaccines, Dr. Lieberman noted.

In 2004, a data review by the Institute of Medicine determined that “the evidence favors rejection of a causal relationship” between thimerosal-containing vaccines and autism.

But judging by some of the public comments at the meeting, not everyone is convinced. Lyn Redwood, R.N., president and cofounder of a nonprofit organization called Sensible Action for Ending Mercury-Induced Neurological Disorders (SafeMinds), urged the ACIP to stop recommending any vaccines that contain thimerosal. She read a list of titles from published scientific articles, such as “Thimerosal Neurotoxicity Is Associated With Glutathione Depletion: Protection With Glutathione Precursors” (Neurotoxicology 2005;26:1–8).

“I just don't see how the committee can avoid these types of studies and cherry-pick the data,” said Ms. Redwood, who has a son diagnosed with pervasive developmental disorder.

More data from the Vaccine Safety Datalink Project are due out soon. This time, the CDC will look at children born from 1994 through 1999—the period when thimerosal-containing vaccines were used frequently. Prenatal and postnatal mercury exposure up to 7 months of age will be quantified, and a variety of assessments for autism and various measures of cognition will be performed.

Dr. Lieberman has financial relationships with Merck & Co., MedImmune, GlaxoSmithKline, and Sanofi Pasteur.

ATLANTA — Recent efforts to broaden influenza immunization among children have kept the thimerosal/autism issue on the front burner for the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The link was evident at the ACIP's winter meeting, where plans were discussed to expand the recommended age range to receive annual flu shots from the current 6 months-5 years to children up through age 18. This could happen as soon as the 2008–2009 influenza season (see story above).

Most routine childhood vaccines no longer contain thimerosal, but influenza vaccine remains a notable exception: Only the intranasal vaccine and one brand of injectable influenza vaccine are currently thimerosal free, while the rest still contain small amounts. All of the influenza vaccine manufacturers are working toward producing preservative-free vaccine, and greater capacity is expected over the next 3–5 years, Dr. Anthony Fiore of the CDC's National Center for Influenza and Respiratory Diseases told the committee.

In the meantime, activist groups claiming a link between thimerosal and the documented rise in the number of children being diagnosed with autism spectrum disorders have kept the issue in the news and on the ACIP's agenda. The committee's 2007–2008 influenza statement will specifically state that “no scientifically conclusive evidence has demonstrated harm from exposure to thimerosal preservative-containing vaccine” and that individuals receiving influenza vaccine may be given “any age- and risk-factor appropriate vaccine preparation, depending on availability.”

At the committee's request, Dr. Jay M. Lieberman presented a summary of the evidence regarding autism and thimerosal, an organic preservative containing 50% ethylmercury that once was commonly used in multidose vaccine containers to prevent microbial growth.

In 1999, the American Academy of Pediatrics and the U.S. Food and Drug Administration urged manufacturers to remove thimerosal from vaccines as quickly as possible, because of the discovery that young children receiving multiple immunizations could exceed the total mercury exposure level recommended by the Environmental Protection Agency, said Dr. Lieberman, chief of pediatric infectious diseases at Miller Children's Hospital, Long Beach, Calif.

In a subsequent statement, the CDC noted that the goal of removing thimerosal from vaccines was “established as a precautionary measure to maintain the public's trust in immunization,” and that “there was no evidence of any harm caused by the low levels in vaccines, but removal would make vaccines safer” (MMWR 2000;49:622).

The relevant data come primarily from cohort and ecological studies. In a population-based cohort study of all 467,450 children born in Denmark during 1990–1996, the risk of autism and autism spectrum disorders did not differ significantly between those vaccinated with thimerosal-containing vaccines and those who received the thimerosal-free versions, and there was no evidence for a dose-response association (JAMA 2003;290:1763–6).

Preliminary data from a 1999 “screening study” of more than 140,000 U.S. children in the Vaccine Safety Datalink Project did suggest an association between thimerosal exposure and “any neurodevelopmental disorder”—but not autism—at 3 months. Those initial results have been widely quoted by activists as evidence for the dangers of thimerosal. However, the study showed no clear association between infant exposure to thimerosal and specific neurodevelopmental disorders. After various methodological errors and issues were resolved, the final published version of the report was less conclusive (Pediatrics 2003;11:1039–48).

“It's important to note that this study was undertaken to identify outcomes that warranted additional study. The authors recognized that there were likely to be other important factors that couldn't be addressed in this study design,” Dr. Lieberman said.

While the increase in the incidence and prevalence of autism spectrum disorders in the United States during the 1980s and 1990s paralleled exposure to thimerosal-containing vaccines, the story is different in Denmark and Sweden, where rates of autism continued to rise even after thimerosal was removed from vaccines (Am. J. Prev. Med. 2003;25:101–6 and Pediatrics 2003;112:604–6). Similarly, emerging data in the United States suggest that autism rates have not decreased with the removal of thimerosal from routine childhood vaccines, Dr. Lieberman noted.

In 2004, a data review by the Institute of Medicine determined that “the evidence favors rejection of a causal relationship” between thimerosal-containing vaccines and autism.

But judging by some of the public comments at the meeting, not everyone is convinced. Lyn Redwood, R.N., president and cofounder of a nonprofit organization called Sensible Action for Ending Mercury-Induced Neurological Disorders (SafeMinds), urged the ACIP to stop recommending any vaccines that contain thimerosal. She read a list of titles from published scientific articles, such as “Thimerosal Neurotoxicity Is Associated With Glutathione Depletion: Protection With Glutathione Precursors” (Neurotoxicology 2005;26:1–8).

“I just don't see how the committee can avoid these types of studies and cherry-pick the data,” said Ms. Redwood, who has a son diagnosed with pervasive developmental disorder.

More data from the Vaccine Safety Datalink Project are due out soon. This time, the CDC will look at children born from 1994 through 1999—the period when thimerosal-containing vaccines were used frequently. Prenatal and postnatal mercury exposure up to 7 months of age will be quantified, and a variety of assessments for autism and various measures of cognition will be performed.

Dr. Lieberman has financial relationships with Merck & Co., MedImmune, GlaxoSmithKline, and Sanofi Pasteur.

ATLANTA — Children aged 6 months to 9 years of age who did not receive two doses of vaccine the first time they were immunized against influenza should receive two doses the following season, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended at its winter meeting.

That was the only major change made to the ACIP's annual influenza statement, approved by the committee at the meeting. No new age or risk groups recommended for routine immunization were added this time around.

For an adequate immune response, children aged 6 months through 9 years receiving influenza vaccine for the first time are supposed to receive two doses given at least a month apart. But, in situations where a child only receives one dose, two studies published in 2006 suggest that protection against influenza is greater with two doses the following year, Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases told the committee.

In one study, when the influenza B antigen was changed for the second season, children who only received one dose in their first season of being vaccinated and one dose in their second season had decreased immunologic response to the influenza B antigen compared with children who received two doses (Pediatrics 2006;118:e579–85).

The other study showed that, in consecutive seasons when the influenza vaccine antigens were unchanged, effectiveness against influenzalike illness in the second season was significantly less for 6− to 21-month-old children being vaccinated for the first time who received one dose in both seasons, compared with 6− to 21-month-olds who received one dose in their first season and two doses in their second season (J. Pediatr. 2006;149:755–62).

The new ACIP recommendation brings it in line with the American Academy of Pediatrics, which issued the same guideline in October 2006.

The American Academy of Family Physicians, which usually follows ACIP's recommendations, will likely change its advice as well, AAFP coliaison Dr. Doug Campos-Outcalt said in an interview.

Although no other major changes were made to the 2007 influenza statement, it will contain some new language. More direct wording will address the lack of scientifically conclusive evidence demonstrating harm from exposure to thimerosal preservative-containing vaccine, and the recommendation that any age- and risk factor-appropriate preparation is acceptable depending on availability. Prior to its vote on the influenza immunization statement, the ACIP heard a presentation by Dr. Jay M. Lieberman summarizing available data on thimerosal (see accompanying story).

Reinforcement of the need for health care workers to be immunized against influenza will be included in the statement, which also will mention new recommendations from several professional societies that all facilities employing health care workers offer the vaccine and require a written declination for those who chose not to be vaccinated.

New language on the timing of influenza immunization will note that although the ideal time is late September and October, immunization efforts should continue through January and beyond. Peak influenza activity occurs in February or March in most seasons, Dr. Fiore said.

Physicians who treat children should be aware that the ACIP is gearing up to expand its influenza vaccination recommendations beyond the current ages 6 months to 5 years to include all children aged 5–18 years. A meeting is planned for this summer to consider the scientific and implementation issues, with the goal of implementation for the 2008–2009 flu season, Dr. Ban Mishu Allos, the ACIP's influenza immunization task force chair, said.

Indeed, universal annual childhood immunization against influenza is already a stated goal of several national, state, and regional professional health care organizations, including the American College of Obstetricians and Gynecologists, the American Osteopathic Association, the Society for Adolescent Medicine, The National Medical Association, and the Society of Teachers of Family Medicine, Dr. Deborah Wexler, chief of the Immunization Action Coalition, informed the committee at the meeting.

ATLANTA — Children aged 6 months to 9 years of age who did not receive two doses of vaccine the first time they were immunized against influenza should receive two doses the following season, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended at its winter meeting.

That was the only major change made to the ACIP's annual influenza statement, approved by the committee at the meeting. No new age or risk groups recommended for routine immunization were added this time around.

For an adequate immune response, children aged 6 months through 9 years receiving influenza vaccine for the first time are supposed to receive two doses given at least a month apart. But, in situations where a child only receives one dose, two studies published in 2006 suggest that protection against influenza is greater with two doses the following year, Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases told the committee.

In one study, when the influenza B antigen was changed for the second season, children who only received one dose in their first season of being vaccinated and one dose in their second season had decreased immunologic response to the influenza B antigen compared with children who received two doses (Pediatrics 2006;118:e579–85).

The other study showed that, in consecutive seasons when the influenza vaccine antigens were unchanged, effectiveness against influenzalike illness in the second season was significantly less for 6− to 21-month-old children being vaccinated for the first time who received one dose in both seasons, compared with 6− to 21-month-olds who received one dose in their first season and two doses in their second season (J. Pediatr. 2006;149:755–62).

The new ACIP recommendation brings it in line with the American Academy of Pediatrics, which issued the same guideline in October 2006.

The American Academy of Family Physicians, which usually follows ACIP's recommendations, will likely change its advice as well, AAFP coliaison Dr. Doug Campos-Outcalt said in an interview.

Although no other major changes were made to the 2007 influenza statement, it will contain some new language. More direct wording will address the lack of scientifically conclusive evidence demonstrating harm from exposure to thimerosal preservative-containing vaccine, and the recommendation that any age- and risk factor-appropriate preparation is acceptable depending on availability. Prior to its vote on the influenza immunization statement, the ACIP heard a presentation by Dr. Jay M. Lieberman summarizing available data on thimerosal (see accompanying story).

Reinforcement of the need for health care workers to be immunized against influenza will be included in the statement, which also will mention new recommendations from several professional societies that all facilities employing health care workers offer the vaccine and require a written declination for those who chose not to be vaccinated.

New language on the timing of influenza immunization will note that although the ideal time is late September and October, immunization efforts should continue through January and beyond. Peak influenza activity occurs in February or March in most seasons, Dr. Fiore said.

Physicians who treat children should be aware that the ACIP is gearing up to expand its influenza vaccination recommendations beyond the current ages 6 months to 5 years to include all children aged 5–18 years. A meeting is planned for this summer to consider the scientific and implementation issues, with the goal of implementation for the 2008–2009 flu season, Dr. Ban Mishu Allos, the ACIP's influenza immunization task force chair, said.

Indeed, universal annual childhood immunization against influenza is already a stated goal of several national, state, and regional professional health care organizations, including the American College of Obstetricians and Gynecologists, the American Osteopathic Association, the Society for Adolescent Medicine, The National Medical Association, and the Society of Teachers of Family Medicine, Dr. Deborah Wexler, chief of the Immunization Action Coalition, informed the committee at the meeting.

ATLANTA — Children aged 6 months to 9 years of age who did not receive two doses of vaccine the first time they were immunized against influenza should receive two doses the following season, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended at its winter meeting.

That was the only major change made to the ACIP's annual influenza statement, approved by the committee at the meeting. No new age or risk groups recommended for routine immunization were added this time around.

For an adequate immune response, children aged 6 months through 9 years receiving influenza vaccine for the first time are supposed to receive two doses given at least a month apart. But, in situations where a child only receives one dose, two studies published in 2006 suggest that protection against influenza is greater with two doses the following year, Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases told the committee.

In one study, when the influenza B antigen was changed for the second season, children who only received one dose in their first season of being vaccinated and one dose in their second season had decreased immunologic response to the influenza B antigen compared with children who received two doses (Pediatrics 2006;118:e579–85).

The other study showed that, in consecutive seasons when the influenza vaccine antigens were unchanged, effectiveness against influenzalike illness in the second season was significantly less for 6− to 21-month-old children being vaccinated for the first time who received one dose in both seasons, compared with 6− to 21-month-olds who received one dose in their first season and two doses in their second season (J. Pediatr. 2006;149:755–62).

The new ACIP recommendation brings it in line with the American Academy of Pediatrics, which issued the same guideline in October 2006.

The American Academy of Family Physicians, which usually follows ACIP's recommendations, will likely change its advice as well, AAFP coliaison Dr. Doug Campos-Outcalt said in an interview.

Although no other major changes were made to the 2007 influenza statement, it will contain some new language. More direct wording will address the lack of scientifically conclusive evidence demonstrating harm from exposure to thimerosal preservative-containing vaccine, and the recommendation that any age- and risk factor-appropriate preparation is acceptable depending on availability. Prior to its vote on the influenza immunization statement, the ACIP heard a presentation by Dr. Jay M. Lieberman summarizing available data on thimerosal (see accompanying story).

Reinforcement of the need for health care workers to be immunized against influenza will be included in the statement, which also will mention new recommendations from several professional societies that all facilities employing health care workers offer the vaccine and require a written declination for those who chose not to be vaccinated.

New language on the timing of influenza immunization will note that although the ideal time is late September and October, immunization efforts should continue through January and beyond. Peak influenza activity occurs in February or March in most seasons, Dr. Fiore said.

Physicians who treat children should be aware that the ACIP is gearing up to expand its influenza vaccination recommendations beyond the current ages 6 months to 5 years to include all children aged 5–18 years. A meeting is planned for this summer to consider the scientific and implementation issues, with the goal of implementation for the 2008–2009 flu season, Dr. Ban Mishu Allos, the ACIP's influenza immunization task force chair, said.

Indeed, universal annual childhood immunization against influenza is already a stated goal of several national, state, and regional professional health care organizations, including the American College of Obstetricians and Gynecologists, the American Osteopathic Association, the Society for Adolescent Medicine, The National Medical Association, and the Society of Teachers of Family Medicine, Dr. Deborah Wexler, chief of the Immunization Action Coalition, informed the committee at the meeting.

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). Another four confirmed cases of GBS in 13− to 19-year-olds who had received MCV4 more than 6 weeks prior to onset were not included in further analysis, said Dr. Davis, director of the CDC's Immunization Safety Office. The onset interval for the 19 analyzed cases was 2–33 days following immunization. Seventeen of the 19 were aged 11–19 years old. Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, he noted.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11− to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected. With two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively. If these data accurately represent the true magnitude of increased risk after MCV4 vaccination, then there would be an excess of just 0.89 cases per million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11− to 14-year-olds vs. 15− to 19-year-olds: For the younger set, the observed vs. expected is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15− to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season. Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11− to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other hand, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15− to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution,” he said.

More data are needed. A larger study led by Harvard Pilgrim is expected to yield data regarding the risk for GBS following MCV4 in approximately 2 years, the length of time necessary to accumulate cases and attain sufficient statistical power.

Physicians should report any case of Guillain-Barré syndrome in a patient following receipt of Menactra to VAERS, at http://vaers.hhs.gov

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). Another four confirmed cases of GBS in 13− to 19-year-olds who had received MCV4 more than 6 weeks prior to onset were not included in further analysis, said Dr. Davis, director of the CDC's Immunization Safety Office. The onset interval for the 19 analyzed cases was 2–33 days following immunization. Seventeen of the 19 were aged 11–19 years old. Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, he noted.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11− to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected. With two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively. If these data accurately represent the true magnitude of increased risk after MCV4 vaccination, then there would be an excess of just 0.89 cases per million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11− to 14-year-olds vs. 15− to 19-year-olds: For the younger set, the observed vs. expected is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15− to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season. Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11− to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other hand, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15− to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution,” he said.

More data are needed. A larger study led by Harvard Pilgrim is expected to yield data regarding the risk for GBS following MCV4 in approximately 2 years, the length of time necessary to accumulate cases and attain sufficient statistical power.

Physicians should report any case of Guillain-Barré syndrome in a patient following receipt of Menactra to VAERS, at http://vaers.hhs.gov

ATLANTA — Data available thus far suggest that the overall risk for Guillain-Barré syndrome following receipt of the meningococcal conjugate vaccine is not significantly increased, Dr. Robert L. Davis reported at the winter meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

From July 2005 through January 2007, a total of 19 cases of Guillain-Barré syndrome (GBS) occurring within 6 weeks of vaccination with the meningococcal conjugate vaccine (MCV4/Menactra) were reported to the passive Vaccine Adverse Events Reporting System (VAERS). Another four confirmed cases of GBS in 13− to 19-year-olds who had received MCV4 more than 6 weeks prior to onset were not included in further analysis, said Dr. Davis, director of the CDC's Immunization Safety Office. The onset interval for the 19 analyzed cases was 2–33 days following immunization. Seventeen of the 19 were aged 11–19 years old. Information from the eight managed care organizations participating in the Vaccine Safety Datalink (VSD) indicates that approximately 94% of MCV recipients are 11–19 years old, he noted.

In the VSD Rapid Cycle Project from April 2006 through January 2007, there were no cases of GBS reported among vaccine recipients aged 11–19 years old within 6 weeks of vaccination. A total of 0–1 case was expected. However, “not finding any GBS after MCV4 vaccination in 11− to 19-year-olds does not offer substantial reassurance regarding MCV4 safety,” Dr. Davis said.

The overall observed reporting rate for GBS after MCV4 vaccination in VAERS, 1.78 per million person-months, was not higher than expected. With two data sources, the VSD and the Healthcare Utilization Project (HCUP), the expected rates of GBS are 1.13 and 1.11 per million person-months, respectively. If these data accurately represent the true magnitude of increased risk after MCV4 vaccination, then there would be an excess of just 0.89 cases per million doses of MCV4 administered, Dr. Davis said.

However, there was a difference in rate ratio when vaccine recipients were divided by age, 11− to 14-year-olds vs. 15− to 19-year-olds: For the younger set, the observed vs. expected is 1.0/4.2, for a rate ratio of 0.25 when controlled for season. In contrast, among the 15− to 19-year-olds, the observed/expected ratio is 16/6.5, for a rate ratio of 2.48, again controlling for season. Seasonality plays a role by age, because the older group is more likely to receive MCV4 prior to school entry whereas the 11− to 14-year-olds are receiving it year-round, Dr. Davis pointed out.

The data are subject to major limitations. On one hand, the passive nature of VAERS means that underreporting is likely, which would raise the risk estimates. On the other hand, there were no surges in GBS cases reported to VAERS after any of the three notices published in the CDC's Morbidity and Mortality Weekly Report, which would be expected if underreporting were marked, he noted.

“Although there appears to be a small increased risk for GBS after MCV4 vaccination in the 15− to 19-year-old age category, the inherent limitations of VAERS require that these findings be viewed with caution,” he said.

More data are needed. A larger study led by Harvard Pilgrim is expected to yield data regarding the risk for GBS following MCV4 in approximately 2 years, the length of time necessary to accumulate cases and attain sufficient statistical power.

Physicians should report any case of Guillain-Barré syndrome in a patient following receipt of Menactra to VAERS, at http://vaers.hhs.gov