2013 AAAAI Annual Meeting

SAN ANTONIO – Oral and sublingual immunotherapy strategies aren’t yet ready for prime time, but they continue to show promise for inducing tolerance in children with food allergies.

Oral immunotherapy

Preliminary findings from a study of low-dose oral immunotherapy (OIT) for peanut allergy, for example, suggest this approach is an effective early-intervention strategy, Dr. Brian Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a randomized, controlled trial involving 49 peanut-sensitized children aged 9-36 months, both low- and high-dose immunotherapy resulted in a significant reduction in both peanut-specific IgE (psIgE) and skin prick test values after a median of 19 treatments, said Dr. Vickery, who is a pediatric allergist and immunologist at the University of North Carolina at Chapel Hill.

The degree of change was similar in those treated with low-dose and high-dose oral immunotherapy. The low dose slope coefficient for psIgE was -2.53 for the low dose group, compared with –1.63 for the high-dose group; and the low dose slope coefficient for the skin prick test was –0.007, compared with –0.009 for the high-dose group, he said.

Of eight subjects who met the criteria for tolerance evaluation as of the time of Dr. Vickery’s presentation, seven had successfully achieved tolerance and now eat peanut ad lib, he noted.

Study subjects were enrolled within 6 months of their index reaction or demonstration of psIgE greater than 5 kUA/L. After randomization to the low- or high-dose treatment group, they underwent serial analysis of immune responses. After at least 1 year of maintenance oral immunotherapy, clinical tolerance was assessed using a double-blinded placebo-controlled oral food challenge based on predefined clinical and immunologic benchmarks.

The findings are preliminary but suggest that early-intervention peanut oral immunotherapy is a feasible strategy. In addition, low-dose oral immunotherapy – using a 10-fold lower dose of peanut protein (the equivalent of about 1 vs. 10 peanuts comprised the maintenance doses in the low- and high-dose groups, respectively) may be sufficiently immunomodulatory in young children with newly diagnosed peanut allergy, Dr. Vickery said during a press briefing at the meeting.

Furthermore, the findings suggest that such an approach is technically possible in that young children can be recruited and treated in this manner, he noted.

Dr. Robert A. Wood, who is chief of the division of allergy and immunology at Hopkins Children’s Center at Johns Hopkins University, Baltimore, and who also presented oral immunotherapy data, noted during the press briefing that the approach used in this study "is sort of seizing on the opportunity that maybe kids early in life, when their allergy is less established, may be more amenable to treatment."

Peanut allergy that manifests in early childhood typically intensifies over 5-10 years, he explained.

The findings, however, are very preliminary.

"In order for us to really understand the impact of these two doses, we will need to assess all of the endpoints in all of the subjects who are currently enrolled, and then unblind the study at the end of it, and do an assessment to really understand whether low or high dose therapy was effective," Dr. Vickery said.

Sublingual immunotherapy

Sublingual immunotherapy (SLIT) is another promising intervention for food allergic children, according to findings from a study presented by Dr. A. Wesley Burks, who is chair of pediatrics at the University of North Carolina at Chapel Hill and physician in chief of N.C. Children’s Hospital, also in Chapel Hill.

Interim data from that study of 44 patients showed that after 36 months of dosing, peanut SLIT–induced clinical tolerance with concurrent changes in skin testing and peanut-specific immunoglobulin levels.

Of 11 patients who completed 36 months of dosing, 6 passed a peanut oral food challenge to 5,000 mg of peanut protein. The remaining five patients ingested a median of 3,750 mg of peanut protein. After SLIT discontinuation for 1 month, five of six passed an identical oral food challenge, suggesting clinical tolerance.

Children in this study were aged 2-11 years. All received open-label peanut SLIT with a daily maintenance dose of 2 mg of peanut protein, Dr. Burks said.

The findings do not say anything about long-term efficacy of SLIT, but they do show that tolerance can be induced, at least in the short term, Dr. Burke said.

Predictors of tolerance induction

Another study presented by Dr. Burke shed some light on factors associated with induction of tolerance, namely basophil hyporesponsiveness and a low peanut IgE:IgG4 ratio.

In that study of 12 patients who received SLIT and 27 who received OIT, 5 (41.7%) and 18 (66.7%), respectively, developed tolerance following immunotherapy. In the SLIT subjects, basophil responses were significantly lower among those who developed tolerance than among those who did not. This was true for each of the 4 log-fold dilutions of peanut antigen used in the assay, Dr. Burks said.

The vast majority of tolerant subjects (91.3%) had a peanut-IgE:IgG4 ratio below 0.92, compared with only 20% of nontolerant subjects.

All subjects underwent double-blind placebo-controlled food challenges to assess desensitization while they were on daily immunotherapy, and those passing the challenge ceased daily therapy and avoided all peanut products for 4 weeks. At 4 weeks, a second food challenge was administered.

The findings suggest that basophil suppression and the balance of antigen-specific IgE and IgG4 may be important in the development of tolerance following peanut immunotherapy, Dr. Burks said.

Long-term immunotherapy outcomes

One missing piece of the immunotherapy puzzle are data on long-term outcomes, as most studies report only 1-2 year outcomes. Another study presented by Dr. Wood, however, takes a step toward filling the gap – with underwhelming results.

The small study looked at long-term outcomes following milk oral immunotherapy in children, and showed that at 4.5 year follow-up, only about 25% of 32 patients were tolerating at least one serving of milk daily and 25% were consuming only trace amounts or were on strict avoidance mainly because of reactions. About 40% of patients were having frequent reactions to milk, 20% had required epinephrine for reactions, and 30% had experienced systemic reactions.

The patients were treated in two studies during 2006 and 2007 with a dose escalation to 500 mg of milk protein over about 8 weeks, followed by 3 months of maintenance dosing. Dietary milk was introduced in amounts ranging from 500 to 4,000 mg daily based on the results of a double-blind placebo-controlled food challenge.

Of note, one subject who passed a 16-g challenge without symptoms went on to become reactive again and now consumes only minimal milk, Dr. Wood said

In fact, one of the surprising things in this study was that some of the more dramatic failures long-term were in children who had achieved success in the initial studies.

These were children who "looked like absolute successes" at the end of the study, because there were tolerating large amounts of milk, he said.

"We really thought – and we hesitate to use the word "cure" – that they were about as close to cured as we could really imagine. And now, 3-5 years later, they are having anaphylactic reactions and are back on strict milk avoidance," he said.

As a result, the excitement following the initial studies has waned somewhat.

"We had a very high degree of optimism. I’m not saying we lost that optimism, but it is certainly tempered a bit by looking at where these kids now stand 3-5 years out," he said, concluding that more research with respect to long-term outcomes of food oral immunotherapy is needed, including investigation of whether longer treatment would improve outcomes, and whether certain factors can predict response and failure.

"The most important message is that this sort of adds another caveat about why we need more research before we can bring this out to our patient population. A message that I think all of us who are doing this research have come to agree upon is that we need long-term follow-up and that letting these kids go at the end of the study is not the end of the story."

Taken together, the findings of these studies underscore a need for more research regarding SLIT vs. OIT, higher vs. lower dosing, and treatment duration, as well as long-term follow-up, the investigators agreed.

"The message is that what we are doing so far is very encouraging, but it’s not the final answer. Where we need to be to bring this out to the general public is several steps beyond where we are now," Dr. Wood said.

The investigators reported having no disclosures.

SAN ANTONIO – Oral and sublingual immunotherapy strategies aren’t yet ready for prime time, but they continue to show promise for inducing tolerance in children with food allergies.

Oral immunotherapy

Preliminary findings from a study of low-dose oral immunotherapy (OIT) for peanut allergy, for example, suggest this approach is an effective early-intervention strategy, Dr. Brian Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a randomized, controlled trial involving 49 peanut-sensitized children aged 9-36 months, both low- and high-dose immunotherapy resulted in a significant reduction in both peanut-specific IgE (psIgE) and skin prick test values after a median of 19 treatments, said Dr. Vickery, who is a pediatric allergist and immunologist at the University of North Carolina at Chapel Hill.

The degree of change was similar in those treated with low-dose and high-dose oral immunotherapy. The low dose slope coefficient for psIgE was -2.53 for the low dose group, compared with –1.63 for the high-dose group; and the low dose slope coefficient for the skin prick test was –0.007, compared with –0.009 for the high-dose group, he said.

Of eight subjects who met the criteria for tolerance evaluation as of the time of Dr. Vickery’s presentation, seven had successfully achieved tolerance and now eat peanut ad lib, he noted.

Study subjects were enrolled within 6 months of their index reaction or demonstration of psIgE greater than 5 kUA/L. After randomization to the low- or high-dose treatment group, they underwent serial analysis of immune responses. After at least 1 year of maintenance oral immunotherapy, clinical tolerance was assessed using a double-blinded placebo-controlled oral food challenge based on predefined clinical and immunologic benchmarks.

The findings are preliminary but suggest that early-intervention peanut oral immunotherapy is a feasible strategy. In addition, low-dose oral immunotherapy – using a 10-fold lower dose of peanut protein (the equivalent of about 1 vs. 10 peanuts comprised the maintenance doses in the low- and high-dose groups, respectively) may be sufficiently immunomodulatory in young children with newly diagnosed peanut allergy, Dr. Vickery said during a press briefing at the meeting.

Furthermore, the findings suggest that such an approach is technically possible in that young children can be recruited and treated in this manner, he noted.

Dr. Robert A. Wood, who is chief of the division of allergy and immunology at Hopkins Children’s Center at Johns Hopkins University, Baltimore, and who also presented oral immunotherapy data, noted during the press briefing that the approach used in this study "is sort of seizing on the opportunity that maybe kids early in life, when their allergy is less established, may be more amenable to treatment."

Peanut allergy that manifests in early childhood typically intensifies over 5-10 years, he explained.

The findings, however, are very preliminary.

"In order for us to really understand the impact of these two doses, we will need to assess all of the endpoints in all of the subjects who are currently enrolled, and then unblind the study at the end of it, and do an assessment to really understand whether low or high dose therapy was effective," Dr. Vickery said.

Sublingual immunotherapy

Sublingual immunotherapy (SLIT) is another promising intervention for food allergic children, according to findings from a study presented by Dr. A. Wesley Burks, who is chair of pediatrics at the University of North Carolina at Chapel Hill and physician in chief of N.C. Children’s Hospital, also in Chapel Hill.

Interim data from that study of 44 patients showed that after 36 months of dosing, peanut SLIT–induced clinical tolerance with concurrent changes in skin testing and peanut-specific immunoglobulin levels.

Of 11 patients who completed 36 months of dosing, 6 passed a peanut oral food challenge to 5,000 mg of peanut protein. The remaining five patients ingested a median of 3,750 mg of peanut protein. After SLIT discontinuation for 1 month, five of six passed an identical oral food challenge, suggesting clinical tolerance.

Children in this study were aged 2-11 years. All received open-label peanut SLIT with a daily maintenance dose of 2 mg of peanut protein, Dr. Burks said.

The findings do not say anything about long-term efficacy of SLIT, but they do show that tolerance can be induced, at least in the short term, Dr. Burke said.

Predictors of tolerance induction

Another study presented by Dr. Burke shed some light on factors associated with induction of tolerance, namely basophil hyporesponsiveness and a low peanut IgE:IgG4 ratio.

In that study of 12 patients who received SLIT and 27 who received OIT, 5 (41.7%) and 18 (66.7%), respectively, developed tolerance following immunotherapy. In the SLIT subjects, basophil responses were significantly lower among those who developed tolerance than among those who did not. This was true for each of the 4 log-fold dilutions of peanut antigen used in the assay, Dr. Burks said.

The vast majority of tolerant subjects (91.3%) had a peanut-IgE:IgG4 ratio below 0.92, compared with only 20% of nontolerant subjects.

All subjects underwent double-blind placebo-controlled food challenges to assess desensitization while they were on daily immunotherapy, and those passing the challenge ceased daily therapy and avoided all peanut products for 4 weeks. At 4 weeks, a second food challenge was administered.

The findings suggest that basophil suppression and the balance of antigen-specific IgE and IgG4 may be important in the development of tolerance following peanut immunotherapy, Dr. Burks said.

Long-term immunotherapy outcomes

One missing piece of the immunotherapy puzzle are data on long-term outcomes, as most studies report only 1-2 year outcomes. Another study presented by Dr. Wood, however, takes a step toward filling the gap – with underwhelming results.

The small study looked at long-term outcomes following milk oral immunotherapy in children, and showed that at 4.5 year follow-up, only about 25% of 32 patients were tolerating at least one serving of milk daily and 25% were consuming only trace amounts or were on strict avoidance mainly because of reactions. About 40% of patients were having frequent reactions to milk, 20% had required epinephrine for reactions, and 30% had experienced systemic reactions.

The patients were treated in two studies during 2006 and 2007 with a dose escalation to 500 mg of milk protein over about 8 weeks, followed by 3 months of maintenance dosing. Dietary milk was introduced in amounts ranging from 500 to 4,000 mg daily based on the results of a double-blind placebo-controlled food challenge.

Of note, one subject who passed a 16-g challenge without symptoms went on to become reactive again and now consumes only minimal milk, Dr. Wood said

In fact, one of the surprising things in this study was that some of the more dramatic failures long-term were in children who had achieved success in the initial studies.

These were children who "looked like absolute successes" at the end of the study, because there were tolerating large amounts of milk, he said.

"We really thought – and we hesitate to use the word "cure" – that they were about as close to cured as we could really imagine. And now, 3-5 years later, they are having anaphylactic reactions and are back on strict milk avoidance," he said.

As a result, the excitement following the initial studies has waned somewhat.

"We had a very high degree of optimism. I’m not saying we lost that optimism, but it is certainly tempered a bit by looking at where these kids now stand 3-5 years out," he said, concluding that more research with respect to long-term outcomes of food oral immunotherapy is needed, including investigation of whether longer treatment would improve outcomes, and whether certain factors can predict response and failure.

"The most important message is that this sort of adds another caveat about why we need more research before we can bring this out to our patient population. A message that I think all of us who are doing this research have come to agree upon is that we need long-term follow-up and that letting these kids go at the end of the study is not the end of the story."

Taken together, the findings of these studies underscore a need for more research regarding SLIT vs. OIT, higher vs. lower dosing, and treatment duration, as well as long-term follow-up, the investigators agreed.

"The message is that what we are doing so far is very encouraging, but it’s not the final answer. Where we need to be to bring this out to the general public is several steps beyond where we are now," Dr. Wood said.

The investigators reported having no disclosures.

SAN ANTONIO – Oral and sublingual immunotherapy strategies aren’t yet ready for prime time, but they continue to show promise for inducing tolerance in children with food allergies.

Oral immunotherapy

Preliminary findings from a study of low-dose oral immunotherapy (OIT) for peanut allergy, for example, suggest this approach is an effective early-intervention strategy, Dr. Brian Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a randomized, controlled trial involving 49 peanut-sensitized children aged 9-36 months, both low- and high-dose immunotherapy resulted in a significant reduction in both peanut-specific IgE (psIgE) and skin prick test values after a median of 19 treatments, said Dr. Vickery, who is a pediatric allergist and immunologist at the University of North Carolina at Chapel Hill.

The degree of change was similar in those treated with low-dose and high-dose oral immunotherapy. The low dose slope coefficient for psIgE was -2.53 for the low dose group, compared with –1.63 for the high-dose group; and the low dose slope coefficient for the skin prick test was –0.007, compared with –0.009 for the high-dose group, he said.

Of eight subjects who met the criteria for tolerance evaluation as of the time of Dr. Vickery’s presentation, seven had successfully achieved tolerance and now eat peanut ad lib, he noted.

Study subjects were enrolled within 6 months of their index reaction or demonstration of psIgE greater than 5 kUA/L. After randomization to the low- or high-dose treatment group, they underwent serial analysis of immune responses. After at least 1 year of maintenance oral immunotherapy, clinical tolerance was assessed using a double-blinded placebo-controlled oral food challenge based on predefined clinical and immunologic benchmarks.

The findings are preliminary but suggest that early-intervention peanut oral immunotherapy is a feasible strategy. In addition, low-dose oral immunotherapy – using a 10-fold lower dose of peanut protein (the equivalent of about 1 vs. 10 peanuts comprised the maintenance doses in the low- and high-dose groups, respectively) may be sufficiently immunomodulatory in young children with newly diagnosed peanut allergy, Dr. Vickery said during a press briefing at the meeting.

Furthermore, the findings suggest that such an approach is technically possible in that young children can be recruited and treated in this manner, he noted.

Dr. Robert A. Wood, who is chief of the division of allergy and immunology at Hopkins Children’s Center at Johns Hopkins University, Baltimore, and who also presented oral immunotherapy data, noted during the press briefing that the approach used in this study "is sort of seizing on the opportunity that maybe kids early in life, when their allergy is less established, may be more amenable to treatment."

Peanut allergy that manifests in early childhood typically intensifies over 5-10 years, he explained.

The findings, however, are very preliminary.

"In order for us to really understand the impact of these two doses, we will need to assess all of the endpoints in all of the subjects who are currently enrolled, and then unblind the study at the end of it, and do an assessment to really understand whether low or high dose therapy was effective," Dr. Vickery said.

Sublingual immunotherapy

Sublingual immunotherapy (SLIT) is another promising intervention for food allergic children, according to findings from a study presented by Dr. A. Wesley Burks, who is chair of pediatrics at the University of North Carolina at Chapel Hill and physician in chief of N.C. Children’s Hospital, also in Chapel Hill.

Interim data from that study of 44 patients showed that after 36 months of dosing, peanut SLIT–induced clinical tolerance with concurrent changes in skin testing and peanut-specific immunoglobulin levels.

Of 11 patients who completed 36 months of dosing, 6 passed a peanut oral food challenge to 5,000 mg of peanut protein. The remaining five patients ingested a median of 3,750 mg of peanut protein. After SLIT discontinuation for 1 month, five of six passed an identical oral food challenge, suggesting clinical tolerance.

Children in this study were aged 2-11 years. All received open-label peanut SLIT with a daily maintenance dose of 2 mg of peanut protein, Dr. Burks said.

The findings do not say anything about long-term efficacy of SLIT, but they do show that tolerance can be induced, at least in the short term, Dr. Burke said.

Predictors of tolerance induction

Another study presented by Dr. Burke shed some light on factors associated with induction of tolerance, namely basophil hyporesponsiveness and a low peanut IgE:IgG4 ratio.

In that study of 12 patients who received SLIT and 27 who received OIT, 5 (41.7%) and 18 (66.7%), respectively, developed tolerance following immunotherapy. In the SLIT subjects, basophil responses were significantly lower among those who developed tolerance than among those who did not. This was true for each of the 4 log-fold dilutions of peanut antigen used in the assay, Dr. Burks said.

The vast majority of tolerant subjects (91.3%) had a peanut-IgE:IgG4 ratio below 0.92, compared with only 20% of nontolerant subjects.

All subjects underwent double-blind placebo-controlled food challenges to assess desensitization while they were on daily immunotherapy, and those passing the challenge ceased daily therapy and avoided all peanut products for 4 weeks. At 4 weeks, a second food challenge was administered.

The findings suggest that basophil suppression and the balance of antigen-specific IgE and IgG4 may be important in the development of tolerance following peanut immunotherapy, Dr. Burks said.

Long-term immunotherapy outcomes

One missing piece of the immunotherapy puzzle are data on long-term outcomes, as most studies report only 1-2 year outcomes. Another study presented by Dr. Wood, however, takes a step toward filling the gap – with underwhelming results.

The small study looked at long-term outcomes following milk oral immunotherapy in children, and showed that at 4.5 year follow-up, only about 25% of 32 patients were tolerating at least one serving of milk daily and 25% were consuming only trace amounts or were on strict avoidance mainly because of reactions. About 40% of patients were having frequent reactions to milk, 20% had required epinephrine for reactions, and 30% had experienced systemic reactions.

The patients were treated in two studies during 2006 and 2007 with a dose escalation to 500 mg of milk protein over about 8 weeks, followed by 3 months of maintenance dosing. Dietary milk was introduced in amounts ranging from 500 to 4,000 mg daily based on the results of a double-blind placebo-controlled food challenge.

Of note, one subject who passed a 16-g challenge without symptoms went on to become reactive again and now consumes only minimal milk, Dr. Wood said

In fact, one of the surprising things in this study was that some of the more dramatic failures long-term were in children who had achieved success in the initial studies.

These were children who "looked like absolute successes" at the end of the study, because there were tolerating large amounts of milk, he said.

"We really thought – and we hesitate to use the word "cure" – that they were about as close to cured as we could really imagine. And now, 3-5 years later, they are having anaphylactic reactions and are back on strict milk avoidance," he said.

As a result, the excitement following the initial studies has waned somewhat.

"We had a very high degree of optimism. I’m not saying we lost that optimism, but it is certainly tempered a bit by looking at where these kids now stand 3-5 years out," he said, concluding that more research with respect to long-term outcomes of food oral immunotherapy is needed, including investigation of whether longer treatment would improve outcomes, and whether certain factors can predict response and failure.

"The most important message is that this sort of adds another caveat about why we need more research before we can bring this out to our patient population. A message that I think all of us who are doing this research have come to agree upon is that we need long-term follow-up and that letting these kids go at the end of the study is not the end of the story."

Taken together, the findings of these studies underscore a need for more research regarding SLIT vs. OIT, higher vs. lower dosing, and treatment duration, as well as long-term follow-up, the investigators agreed.

"The message is that what we are doing so far is very encouraging, but it’s not the final answer. Where we need to be to bring this out to the general public is several steps beyond where we are now," Dr. Wood said.

The investigators reported having no disclosures.

SAN ANTONIO – Children living in the United States who were born elsewhere initially have lower rates of allergic disease than do those born in the United States, but the protection against allergic disease is lost after prolonged U.S. residence, according to an analysis of data from the 2007-2008 National Survey of Children’s Health.

Of 91,642 children aged 0-17 years who were included in the study, those born outside of the United States had significantly lower odds of having any allergic disorder, compared with those born in the United States (odds ratio, 0.48). They also had lower odds of all individual allergic disorders studied, including prior or current asthma (OR 0.53), current asthma (OR 0.34), eczema (OR 0.43), hay fever (OR 0.39), and food allergy (OR 0.60), Dr. Jonathan I. Silverberg reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The association remained significant after adjustment for age, sex, race/ethnicity, household income, residence in metropolitan areas, and history of moving to a new U.S. residence, said Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

Also of note, the prevalence rates of allergic disease were lower for all of the diseases studied for children born outside of the United States whose parents were born outside of the United States, compared with those whose parents were born in the United States.

However, after 10 years or more of United States residence, children born outside of the United States had significantly higher odds of developing an allergic disorder, compared with those born outside of the United States who had lived in the country for only 0-2 years (OR 3.04). This was true for eczema (OR 4.93) and hay fever (OR 6.25), but not for asthma or food allergy, Dr. Silverberg said.

The study was undertaken in the wake of prior data showing that certain racial or ethnic groups have lower rates of allergic disease. Dr. Silverberg and his colleagues set out to investigate whether an association existed between birthplace, length of U.S. residence, and various allergic diseases.

The findings suggest that environmental factors promote the development of allergic disease, he concluded.

Dr. Silverberg reported having no relevant financial disclosures.

SAN ANTONIO – Children living in the United States who were born elsewhere initially have lower rates of allergic disease than do those born in the United States, but the protection against allergic disease is lost after prolonged U.S. residence, according to an analysis of data from the 2007-2008 National Survey of Children’s Health.

Of 91,642 children aged 0-17 years who were included in the study, those born outside of the United States had significantly lower odds of having any allergic disorder, compared with those born in the United States (odds ratio, 0.48). They also had lower odds of all individual allergic disorders studied, including prior or current asthma (OR 0.53), current asthma (OR 0.34), eczema (OR 0.43), hay fever (OR 0.39), and food allergy (OR 0.60), Dr. Jonathan I. Silverberg reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The association remained significant after adjustment for age, sex, race/ethnicity, household income, residence in metropolitan areas, and history of moving to a new U.S. residence, said Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

Also of note, the prevalence rates of allergic disease were lower for all of the diseases studied for children born outside of the United States whose parents were born outside of the United States, compared with those whose parents were born in the United States.

However, after 10 years or more of United States residence, children born outside of the United States had significantly higher odds of developing an allergic disorder, compared with those born outside of the United States who had lived in the country for only 0-2 years (OR 3.04). This was true for eczema (OR 4.93) and hay fever (OR 6.25), but not for asthma or food allergy, Dr. Silverberg said.

The study was undertaken in the wake of prior data showing that certain racial or ethnic groups have lower rates of allergic disease. Dr. Silverberg and his colleagues set out to investigate whether an association existed between birthplace, length of U.S. residence, and various allergic diseases.

The findings suggest that environmental factors promote the development of allergic disease, he concluded.

Dr. Silverberg reported having no relevant financial disclosures.

SAN ANTONIO – Children living in the United States who were born elsewhere initially have lower rates of allergic disease than do those born in the United States, but the protection against allergic disease is lost after prolonged U.S. residence, according to an analysis of data from the 2007-2008 National Survey of Children’s Health.

Of 91,642 children aged 0-17 years who were included in the study, those born outside of the United States had significantly lower odds of having any allergic disorder, compared with those born in the United States (odds ratio, 0.48). They also had lower odds of all individual allergic disorders studied, including prior or current asthma (OR 0.53), current asthma (OR 0.34), eczema (OR 0.43), hay fever (OR 0.39), and food allergy (OR 0.60), Dr. Jonathan I. Silverberg reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The association remained significant after adjustment for age, sex, race/ethnicity, household income, residence in metropolitan areas, and history of moving to a new U.S. residence, said Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

Also of note, the prevalence rates of allergic disease were lower for all of the diseases studied for children born outside of the United States whose parents were born outside of the United States, compared with those whose parents were born in the United States.

However, after 10 years or more of United States residence, children born outside of the United States had significantly higher odds of developing an allergic disorder, compared with those born outside of the United States who had lived in the country for only 0-2 years (OR 3.04). This was true for eczema (OR 4.93) and hay fever (OR 6.25), but not for asthma or food allergy, Dr. Silverberg said.

The study was undertaken in the wake of prior data showing that certain racial or ethnic groups have lower rates of allergic disease. Dr. Silverberg and his colleagues set out to investigate whether an association existed between birthplace, length of U.S. residence, and various allergic diseases.

The findings suggest that environmental factors promote the development of allergic disease, he concluded.

Dr. Silverberg reported having no relevant financial disclosures.

SAN ANTONIO – Overweight and obese children in need of epinephrine for anaphylaxis should be injected in the calf or in the lower thigh, rather than upper half of the thigh, to ensure intramuscular administration, according to findings from an ultrasound study of 93 children.

Ultrasound measurement demonstrated that the distance from skin surface to muscle depth was greater than auto-injector needle length at one quarter of the distance down the thigh in 82% of obese children vs. 25% of nonobese children. At three-quarters of the way down the thigh, this was the case in only 17% of obese children and 2% of nonobese children, Dr. Peter Arkwright reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

At a point midway down the calf, the skin surface to muscle depth was less than the length of the auto-injector needle in all of the children, said Dr. Arkwright of the University of Manchester (England).

Intramuscular injection, rather than subcutaneous injection, is imperative for effective delivery of epinephrine, he said, noting that this study was undertaken because of growing concerns that increasing obesity among children could make existing auto-injectors inadequate for providing intramuscular delivery in a significant proportion of patients.

Children included in the study were patients from regional pediatric allergy clinics. All were measured for height, weight, and body mass index, and all underwent ultrasound measurement at set distances down the thigh and leg. Higher weight, BMI, and waist circumference – but not age or gender – were associated with skin surface to muscle depth greater than auto-injector needle length, he noted.

"Based on our study, injecting epinephrine into the lower rather than upper thigh would be advised in overweight or obese children," he said, adding that caregivers of children at risk of anaphylaxis should be advised about the importance of administering epinephrine into the muscle in the most effective way.

For overweight and obese children, this involves injecting into the lower half of the thigh, and for very obese children it involves injecting at the middle of the calf, he said.

Dr. Arkwright reported having no disclosures.

SAN ANTONIO – Overweight and obese children in need of epinephrine for anaphylaxis should be injected in the calf or in the lower thigh, rather than upper half of the thigh, to ensure intramuscular administration, according to findings from an ultrasound study of 93 children.

Ultrasound measurement demonstrated that the distance from skin surface to muscle depth was greater than auto-injector needle length at one quarter of the distance down the thigh in 82% of obese children vs. 25% of nonobese children. At three-quarters of the way down the thigh, this was the case in only 17% of obese children and 2% of nonobese children, Dr. Peter Arkwright reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

At a point midway down the calf, the skin surface to muscle depth was less than the length of the auto-injector needle in all of the children, said Dr. Arkwright of the University of Manchester (England).

Intramuscular injection, rather than subcutaneous injection, is imperative for effective delivery of epinephrine, he said, noting that this study was undertaken because of growing concerns that increasing obesity among children could make existing auto-injectors inadequate for providing intramuscular delivery in a significant proportion of patients.

Children included in the study were patients from regional pediatric allergy clinics. All were measured for height, weight, and body mass index, and all underwent ultrasound measurement at set distances down the thigh and leg. Higher weight, BMI, and waist circumference – but not age or gender – were associated with skin surface to muscle depth greater than auto-injector needle length, he noted.

"Based on our study, injecting epinephrine into the lower rather than upper thigh would be advised in overweight or obese children," he said, adding that caregivers of children at risk of anaphylaxis should be advised about the importance of administering epinephrine into the muscle in the most effective way.

For overweight and obese children, this involves injecting into the lower half of the thigh, and for very obese children it involves injecting at the middle of the calf, he said.

Dr. Arkwright reported having no disclosures.

SAN ANTONIO – Overweight and obese children in need of epinephrine for anaphylaxis should be injected in the calf or in the lower thigh, rather than upper half of the thigh, to ensure intramuscular administration, according to findings from an ultrasound study of 93 children.

Ultrasound measurement demonstrated that the distance from skin surface to muscle depth was greater than auto-injector needle length at one quarter of the distance down the thigh in 82% of obese children vs. 25% of nonobese children. At three-quarters of the way down the thigh, this was the case in only 17% of obese children and 2% of nonobese children, Dr. Peter Arkwright reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

At a point midway down the calf, the skin surface to muscle depth was less than the length of the auto-injector needle in all of the children, said Dr. Arkwright of the University of Manchester (England).

Intramuscular injection, rather than subcutaneous injection, is imperative for effective delivery of epinephrine, he said, noting that this study was undertaken because of growing concerns that increasing obesity among children could make existing auto-injectors inadequate for providing intramuscular delivery in a significant proportion of patients.

Children included in the study were patients from regional pediatric allergy clinics. All were measured for height, weight, and body mass index, and all underwent ultrasound measurement at set distances down the thigh and leg. Higher weight, BMI, and waist circumference – but not age or gender – were associated with skin surface to muscle depth greater than auto-injector needle length, he noted.

"Based on our study, injecting epinephrine into the lower rather than upper thigh would be advised in overweight or obese children," he said, adding that caregivers of children at risk of anaphylaxis should be advised about the importance of administering epinephrine into the muscle in the most effective way.

For overweight and obese children, this involves injecting into the lower half of the thigh, and for very obese children it involves injecting at the middle of the calf, he said.

Dr. Arkwright reported having no disclosures.

SAN ANTONIO – A diagnosis of asthma, allergic disease, or obstructive or restrictive lung disease among participants in the first National Health and Nutrition Examination Survey conferred a significantly increased long-term risk of all-cause mortality for adults who were aged 40-75 years at baseline but not for those who were aged 25-39 years at baseline, according to findings from the study.

A diagnosis of asthma in the younger group conferred an increased long-term risk of death due to respiratory causes – as did a diagnosis of asthma in the older group, Dr. Jessica R. Savage reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

"This association was not likely explained by underlying bronchitis or an increased risk of death due to respiratory infection but was likely due to asthma itself," said Dr. Savage of Brigham and Women’s Hospital, Boston.

"I think the main conclusions are reassuring – no increase in mortality if you are young and have allergies. Some studies show an association between allergy and stroke/heart disease. We were worried that with the rising increase in allergy, there would be also an increase in these other diseases. But we did not see that, fortunately.

"We saw an association with asthma and respiratory death even in the young. Of course, one always needs to remember to be vigilant with asthmatics, but overall for young people the news is good," she said during an interview.

Data were obtained from the National Health and Nutrition Examination Survey (NHANES I), which was conducted from 1971 to 1975 and included 31,937 adults. Of these participants, 14,407 were included in the NHANES I Epidemiologic Follow-Up Study (NHEFS) and were assessed for doctor-diagnosed asthma, allergic rhinitis, food allergy, and urticaria. A subcohort of 6,913 subjects received a more detailed health interview and examination, including prebronchodilator spirometry and percent predicted forced expiratory volume and forced vital capacity. Vital status and cause of death were obtained in 2006.

After adjustment for age, gender, income, education, race, and smoking history, a sensitivity analysis for the association between asthma and mortality demonstrated a significantly increased long-term risk of death in those who were aged 40-75 years at baseline (hazard ratio, 1.22), but not for those aged 25-29 years at baseline (HR, 1.20). The hazard ratios for all-cause mortality in these groups, after exclusion of subjects with bronchitis were not statistically significant (1.16 and 1.52, respectively).

Hazard ratios for the association between asthma and respiratory mortality were significant at 2.03 and 5.87 for the older and younger groups, respectively. The hazard ratios for these groups remained statistically significant at 8.56 and 1.82, respectively, after exclusion of subjects with bronchitis.

This study also demonstrated that older subjects with obstructive lung disease were at significantly increased risk of both all-cause and respiratory mortality and that older subjects with restrictive lung disease were at significantly increased risk of both all-cause and cardiovascular mortality.

Conversely, older adults with urticaria had a reduced risk of cardiovascular mortality.

Cancer-related mortality was slightly, but not significantly, increased in the younger subjects diagnosed with urticaria, and in the older subjects diagnosed with asthma or moderate to severe lung obstruction.

"Asthma and allergic diseases, which typically manifest in childhood, have increased in the United States over the last 3 decades. Asthma and allergy may increase mortality by directly reducing lung function or may be markers of immune dysregulation that could lead to systemic inflammation," Dr. Savage noted, adding that although prior studies have demonstrated associations between allergic sensitization and stroke, hives and cancer, asthma and mortality, and obstructive lung disease and cardiovascular events, the effects of asthma and allergic disease on long-term mortality have been unclear.

"The findings (of this follow-up study) provide some insight regarding the effects of asthma and allergic disease on long-term mortality, Dr. Savage said.

The NHEFS is a joint project of the National Center for Health Statistics and the National Institute on Aging in collaboration with other agencies of the U.S. Public Health Service. Dr. Savage reported having no disclosures.

SAN ANTONIO – A diagnosis of asthma, allergic disease, or obstructive or restrictive lung disease among participants in the first National Health and Nutrition Examination Survey conferred a significantly increased long-term risk of all-cause mortality for adults who were aged 40-75 years at baseline but not for those who were aged 25-39 years at baseline, according to findings from the study.

A diagnosis of asthma in the younger group conferred an increased long-term risk of death due to respiratory causes – as did a diagnosis of asthma in the older group, Dr. Jessica R. Savage reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

"This association was not likely explained by underlying bronchitis or an increased risk of death due to respiratory infection but was likely due to asthma itself," said Dr. Savage of Brigham and Women’s Hospital, Boston.

"I think the main conclusions are reassuring – no increase in mortality if you are young and have allergies. Some studies show an association between allergy and stroke/heart disease. We were worried that with the rising increase in allergy, there would be also an increase in these other diseases. But we did not see that, fortunately.

"We saw an association with asthma and respiratory death even in the young. Of course, one always needs to remember to be vigilant with asthmatics, but overall for young people the news is good," she said during an interview.

Data were obtained from the National Health and Nutrition Examination Survey (NHANES I), which was conducted from 1971 to 1975 and included 31,937 adults. Of these participants, 14,407 were included in the NHANES I Epidemiologic Follow-Up Study (NHEFS) and were assessed for doctor-diagnosed asthma, allergic rhinitis, food allergy, and urticaria. A subcohort of 6,913 subjects received a more detailed health interview and examination, including prebronchodilator spirometry and percent predicted forced expiratory volume and forced vital capacity. Vital status and cause of death were obtained in 2006.

After adjustment for age, gender, income, education, race, and smoking history, a sensitivity analysis for the association between asthma and mortality demonstrated a significantly increased long-term risk of death in those who were aged 40-75 years at baseline (hazard ratio, 1.22), but not for those aged 25-29 years at baseline (HR, 1.20). The hazard ratios for all-cause mortality in these groups, after exclusion of subjects with bronchitis were not statistically significant (1.16 and 1.52, respectively).

Hazard ratios for the association between asthma and respiratory mortality were significant at 2.03 and 5.87 for the older and younger groups, respectively. The hazard ratios for these groups remained statistically significant at 8.56 and 1.82, respectively, after exclusion of subjects with bronchitis.

This study also demonstrated that older subjects with obstructive lung disease were at significantly increased risk of both all-cause and respiratory mortality and that older subjects with restrictive lung disease were at significantly increased risk of both all-cause and cardiovascular mortality.

Conversely, older adults with urticaria had a reduced risk of cardiovascular mortality.

Cancer-related mortality was slightly, but not significantly, increased in the younger subjects diagnosed with urticaria, and in the older subjects diagnosed with asthma or moderate to severe lung obstruction.

"Asthma and allergic diseases, which typically manifest in childhood, have increased in the United States over the last 3 decades. Asthma and allergy may increase mortality by directly reducing lung function or may be markers of immune dysregulation that could lead to systemic inflammation," Dr. Savage noted, adding that although prior studies have demonstrated associations between allergic sensitization and stroke, hives and cancer, asthma and mortality, and obstructive lung disease and cardiovascular events, the effects of asthma and allergic disease on long-term mortality have been unclear.

"The findings (of this follow-up study) provide some insight regarding the effects of asthma and allergic disease on long-term mortality, Dr. Savage said.

The NHEFS is a joint project of the National Center for Health Statistics and the National Institute on Aging in collaboration with other agencies of the U.S. Public Health Service. Dr. Savage reported having no disclosures.

SAN ANTONIO – A diagnosis of asthma, allergic disease, or obstructive or restrictive lung disease among participants in the first National Health and Nutrition Examination Survey conferred a significantly increased long-term risk of all-cause mortality for adults who were aged 40-75 years at baseline but not for those who were aged 25-39 years at baseline, according to findings from the study.

A diagnosis of asthma in the younger group conferred an increased long-term risk of death due to respiratory causes – as did a diagnosis of asthma in the older group, Dr. Jessica R. Savage reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

"This association was not likely explained by underlying bronchitis or an increased risk of death due to respiratory infection but was likely due to asthma itself," said Dr. Savage of Brigham and Women’s Hospital, Boston.

"I think the main conclusions are reassuring – no increase in mortality if you are young and have allergies. Some studies show an association between allergy and stroke/heart disease. We were worried that with the rising increase in allergy, there would be also an increase in these other diseases. But we did not see that, fortunately.

"We saw an association with asthma and respiratory death even in the young. Of course, one always needs to remember to be vigilant with asthmatics, but overall for young people the news is good," she said during an interview.

Data were obtained from the National Health and Nutrition Examination Survey (NHANES I), which was conducted from 1971 to 1975 and included 31,937 adults. Of these participants, 14,407 were included in the NHANES I Epidemiologic Follow-Up Study (NHEFS) and were assessed for doctor-diagnosed asthma, allergic rhinitis, food allergy, and urticaria. A subcohort of 6,913 subjects received a more detailed health interview and examination, including prebronchodilator spirometry and percent predicted forced expiratory volume and forced vital capacity. Vital status and cause of death were obtained in 2006.

After adjustment for age, gender, income, education, race, and smoking history, a sensitivity analysis for the association between asthma and mortality demonstrated a significantly increased long-term risk of death in those who were aged 40-75 years at baseline (hazard ratio, 1.22), but not for those aged 25-29 years at baseline (HR, 1.20). The hazard ratios for all-cause mortality in these groups, after exclusion of subjects with bronchitis were not statistically significant (1.16 and 1.52, respectively).

Hazard ratios for the association between asthma and respiratory mortality were significant at 2.03 and 5.87 for the older and younger groups, respectively. The hazard ratios for these groups remained statistically significant at 8.56 and 1.82, respectively, after exclusion of subjects with bronchitis.

This study also demonstrated that older subjects with obstructive lung disease were at significantly increased risk of both all-cause and respiratory mortality and that older subjects with restrictive lung disease were at significantly increased risk of both all-cause and cardiovascular mortality.

Conversely, older adults with urticaria had a reduced risk of cardiovascular mortality.

Cancer-related mortality was slightly, but not significantly, increased in the younger subjects diagnosed with urticaria, and in the older subjects diagnosed with asthma or moderate to severe lung obstruction.

"Asthma and allergic diseases, which typically manifest in childhood, have increased in the United States over the last 3 decades. Asthma and allergy may increase mortality by directly reducing lung function or may be markers of immune dysregulation that could lead to systemic inflammation," Dr. Savage noted, adding that although prior studies have demonstrated associations between allergic sensitization and stroke, hives and cancer, asthma and mortality, and obstructive lung disease and cardiovascular events, the effects of asthma and allergic disease on long-term mortality have been unclear.

"The findings (of this follow-up study) provide some insight regarding the effects of asthma and allergic disease on long-term mortality, Dr. Savage said.

The NHEFS is a joint project of the National Center for Health Statistics and the National Institute on Aging in collaboration with other agencies of the U.S. Public Health Service. Dr. Savage reported having no disclosures.

SAN ANTONIO – More of the children who present to the pediatric emergency department with asthma exacerbation received recommended care when the staff had instituted a nurse-initiated, evidence-based, standardized order set, according to Dr. Moira E. Breslin.

Specifically, the percentage of patients receiving at least one dose of ipratropium bromide improved from 55.4% before implementation of the order set to 90.9% after implementation. Compliance with the recommendation of the National Asthma Guidelines that patients receive three consecutive nebulized treatments of ipratropium bromide increased from 13.5% to 40.9%, Dr. Breslin of Duke University Medical Center, Durham, N.C., reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The median time to delivery of rescue medication also improved from 21 minutes to 14 minutes for first inhaled bronchodilator administration, and from 41 minutes to 19 minutes for delivery of systemic corticosteroids.

All differences were statistically significant.

The findings are based on a review of charts for 193 patients treated in the pediatric emergency department for status asthmaticus before implementation of the evidence-based standardized order set, or EBSOS, (between Feb. 23, 2009, and Feb. 22, 2012), and for 22 patients treated after implementation (between Feb. 23, 2012, and July 31, 2012).

The EBSOS for the treatment of pediatric asthma used in this study was developed and incorporated into the emergency department electronic ordering system because personnel were not consistently following national asthma treatment guidelines, according to a separate 2010 emergency department records review.

That review showed that 24% of patients admitted for status asthmaticus had not received the recommended ipratropium bromide treatment, and that only 14% of those who did receive ipratropium bromide received the recommended three consecutive doses.

Implementation of the EBSOS involved the use of an algorithm based on a validated Modified Pulmonary Index Score that allowed for triage nurse initiation of the EBSOS. The EBSOS called for continuous pulse oximetry, supplemental oxygen as needed, evaluation by a respiratory therapist, nebulized albuterol administration at 5 mg every 20 minutes for three treatments, administration of nebulized ipratropium bromide at 0.5 mg every 20 minutes for three treatments, and administration of one dose of oral prednisolone at 2 mg/kg up to a maximum of 60 mg.

"Implementation of an EBSOS improved compliance to national asthma guidelines, as evidenced by a higher proportion of pediatric emergency department patients in status asthmaticus receiving ipratropium bromide, as well as shortened time to delivery of inhaled bronchodilators and systemic steroids," Dr. Breslin concluded, noting that future analysis of this review will focus on patient-centered outcomes.

Dr. Breslin reported having no relevant financial disclosures

SAN ANTONIO – More of the children who present to the pediatric emergency department with asthma exacerbation received recommended care when the staff had instituted a nurse-initiated, evidence-based, standardized order set, according to Dr. Moira E. Breslin.

Specifically, the percentage of patients receiving at least one dose of ipratropium bromide improved from 55.4% before implementation of the order set to 90.9% after implementation. Compliance with the recommendation of the National Asthma Guidelines that patients receive three consecutive nebulized treatments of ipratropium bromide increased from 13.5% to 40.9%, Dr. Breslin of Duke University Medical Center, Durham, N.C., reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The median time to delivery of rescue medication also improved from 21 minutes to 14 minutes for first inhaled bronchodilator administration, and from 41 minutes to 19 minutes for delivery of systemic corticosteroids.

All differences were statistically significant.

The findings are based on a review of charts for 193 patients treated in the pediatric emergency department for status asthmaticus before implementation of the evidence-based standardized order set, or EBSOS, (between Feb. 23, 2009, and Feb. 22, 2012), and for 22 patients treated after implementation (between Feb. 23, 2012, and July 31, 2012).

The EBSOS for the treatment of pediatric asthma used in this study was developed and incorporated into the emergency department electronic ordering system because personnel were not consistently following national asthma treatment guidelines, according to a separate 2010 emergency department records review.

That review showed that 24% of patients admitted for status asthmaticus had not received the recommended ipratropium bromide treatment, and that only 14% of those who did receive ipratropium bromide received the recommended three consecutive doses.

Implementation of the EBSOS involved the use of an algorithm based on a validated Modified Pulmonary Index Score that allowed for triage nurse initiation of the EBSOS. The EBSOS called for continuous pulse oximetry, supplemental oxygen as needed, evaluation by a respiratory therapist, nebulized albuterol administration at 5 mg every 20 minutes for three treatments, administration of nebulized ipratropium bromide at 0.5 mg every 20 minutes for three treatments, and administration of one dose of oral prednisolone at 2 mg/kg up to a maximum of 60 mg.

"Implementation of an EBSOS improved compliance to national asthma guidelines, as evidenced by a higher proportion of pediatric emergency department patients in status asthmaticus receiving ipratropium bromide, as well as shortened time to delivery of inhaled bronchodilators and systemic steroids," Dr. Breslin concluded, noting that future analysis of this review will focus on patient-centered outcomes.

Dr. Breslin reported having no relevant financial disclosures

SAN ANTONIO – More of the children who present to the pediatric emergency department with asthma exacerbation received recommended care when the staff had instituted a nurse-initiated, evidence-based, standardized order set, according to Dr. Moira E. Breslin.

Specifically, the percentage of patients receiving at least one dose of ipratropium bromide improved from 55.4% before implementation of the order set to 90.9% after implementation. Compliance with the recommendation of the National Asthma Guidelines that patients receive three consecutive nebulized treatments of ipratropium bromide increased from 13.5% to 40.9%, Dr. Breslin of Duke University Medical Center, Durham, N.C., reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The median time to delivery of rescue medication also improved from 21 minutes to 14 minutes for first inhaled bronchodilator administration, and from 41 minutes to 19 minutes for delivery of systemic corticosteroids.

All differences were statistically significant.

The findings are based on a review of charts for 193 patients treated in the pediatric emergency department for status asthmaticus before implementation of the evidence-based standardized order set, or EBSOS, (between Feb. 23, 2009, and Feb. 22, 2012), and for 22 patients treated after implementation (between Feb. 23, 2012, and July 31, 2012).

The EBSOS for the treatment of pediatric asthma used in this study was developed and incorporated into the emergency department electronic ordering system because personnel were not consistently following national asthma treatment guidelines, according to a separate 2010 emergency department records review.

That review showed that 24% of patients admitted for status asthmaticus had not received the recommended ipratropium bromide treatment, and that only 14% of those who did receive ipratropium bromide received the recommended three consecutive doses.

Implementation of the EBSOS involved the use of an algorithm based on a validated Modified Pulmonary Index Score that allowed for triage nurse initiation of the EBSOS. The EBSOS called for continuous pulse oximetry, supplemental oxygen as needed, evaluation by a respiratory therapist, nebulized albuterol administration at 5 mg every 20 minutes for three treatments, administration of nebulized ipratropium bromide at 0.5 mg every 20 minutes for three treatments, and administration of one dose of oral prednisolone at 2 mg/kg up to a maximum of 60 mg.

"Implementation of an EBSOS improved compliance to national asthma guidelines, as evidenced by a higher proportion of pediatric emergency department patients in status asthmaticus receiving ipratropium bromide, as well as shortened time to delivery of inhaled bronchodilators and systemic steroids," Dr. Breslin concluded, noting that future analysis of this review will focus on patient-centered outcomes.

Dr. Breslin reported having no relevant financial disclosures

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

©BananaStock/thinkstockphotos.com

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

fpnews@elsevier.com

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

©BananaStock/thinkstockphotos.com

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

fpnews@elsevier.com

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

©BananaStock/thinkstockphotos.com

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

fpnews@elsevier.com

SAN ANTONIO – Omalizumab diminished the signs and symptoms of chronic idiopathic urticaria in a dose-dependent fashion in a phase III study of 323 patients who failed to respond adequately to H1-antihistamines.

After 12 weeks of treatment with the recombinant humanized monoclonal antibody, improvements from baseline in weekly itch-severity scores were significantly greater in patients randomized to receive three doses of either 300 mg or 150 mg every 4 weeks, compared with placebo (score change of -9.8 and -8.1 vs. -5.1, respectively). The itch-severity score in patients randomized to receive a 75-mg dose changed by -5.9 points, but this did not differ significantly from the change in the placebo group, according to Dr. Marcus Maurer of Charite-Universitatsmedizin, Berlin. The report was published online on Feb. 24 in the New England Journal of Medicine.

The findings from this international double-blind trial were reported simultaneously at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In addition to meeting the primary 12-week response endpoint of change in weekly itch-severity score, patients receiving the 300-mg and 150-mg doses of omalizumab also experienced significant improvements, compared with patients given placebo, on all but one secondary endpoint, including change in the 7-day urticaria activity score (UAS7), change in the score for the weekly number of hives, time until a reduction from baseline of at least 5 points in the weekly itch-severity score (the MID), the proportions of patients with a UAS7 of 6 or less, the number of patients with a weekly MID response in the itch-severity score, the change from baseline in the score for the size of the largest hive, and change from baseline in the overall score on the Dermatology Life Quality Index. Those receiving 300 mg, but not those receiving 150 mg, also experienced significant improvement in the proportion of angioedema-free days from weeks 4-12 (N. Engl. J. Med. 2013 Feb. 24 [doi:10.1056/NEJMoa1215372]).

In a post hoc analysis at 12 weeks, 53%, 23%, 18%, and 10%, of those in the 300-mg, 150-mg, 75-mg, and placebo groups, respectively, were completely free of hives, and 44%, 22%, 16%, and 5%, respectively, were free of both hives and itching.

Of note, many patients experienced extremely rapid improvement, raising questions about a potential, as-yet unidentified and fundamental characteristic of this disease, study coauthors Dr. Thomas B. Casale, professor of medicine and medical microbiology and immunology and chief of allergy/immunology at Creighton University Medical Center, Omaha, Neb., and Dr. Allen P. Kaplan, clinical professor of medicine at the Medical University of South Carolina, Charleston, reported during a press briefing at AAAAI.

They explained that omalizumab, currently approved as an add-on therapy for moderate to severe persistent allergic asthma, is known to bind the allergic antibody immunoglobulin E (IgE). Many patients with chronic urticaria have an antibody that binds to a protein on the surface of histamine-containing cells, and that protein binds IgE.

"Just one injection drops one’s IgE level pretty close to zero ... and we learned that when we drop IgE to rock bottom, the protein on the cell to which it is attached also drops – and that’s the protein that the circulating antibody interacts with. The thinking was that if we drop the surface protein low enough, there’s nothing for the antibody to react with, and the hives would improve," he said.

This was, in fact, the case, as demonstrated in a phase I study of 12 patients, in which 7 patients responded dramatically, 4 responded partially, and 1 had no response. These findings led to the current phase III study, which is one of three such studies that investigators hope will lead to the drug’s approval for chronic idiopathic urticaria, because the high cost of the drug is prohibitive with respect to off-label use.

The same effect was seen in the current study.

This effect, however, takes a couple weeks to become apparent, so the rapid responses that occur in numerous patients suggest there is something more at play.

"This is working even faster than we thought, and probably there is a function of the allergic antibody that we do not yet understand," Dr. Kaplan said. "So this is going to be not only a terrific therapy for the disorder, but will lead to research in the future that probably – we hope – will elucidate the underlying abnormality of chronic urticaria beyond our current understanding of it. It’s very exciting, because it might elucidate some fundamental analogy that we don’t appreciate, and would have implications for allergic disease across the board."

The current study comprised patients aged 12-75 years who had a 6-month or longer history of chronic idiopathic urticaria, the presence of hives associated with itching for at least 8 consecutive weeks at any time prior to enrollment (despite H1-antihistamine use), a UAS7 of 16 or more during a 7-day period, a weekly itch-severity score of at least 8, a score of at least 4 on the UAS on at least one of the screening-visit days, and receipt of a licensed dose of a second-generation H1-antihistamine for at least 3 consecutive days immediately prior to the screening visit. Those with a clearly defined underlying cause for their symptoms were excluded. The doses evaluated in this study were based on a prior dose-ranging study, which showed no additional benefit with doses over 300 mg, the investigators said.

Patients continued to receive stable doses of H1-antihistamines throughout the 12-week treatment period, and were permitted to use diphenhydramine as a rescue medication.

Omalizumab was well tolerated in this study, with a similar number of adverse events occurring across the treatment groups. Serious adverse events occurred more often in the 300-mg group, with 6% of patients in that group experiencing a serious adverse event, compared with 3% of patients in the placebo group, and 1% of patients in the 150-mg and 75-mg groups, but the events were not considered to be related to the study drug.

The duration of response, however, was limited, as noted during a 16-week observation period following the initial 12-week treatment period.

Although the weekly itch-severity scores did not return to baseline during follow-up, they did increase to the levels seen in the placebo group.

The findings are nonetheless encouraging, Dr. Kaplan said, noting that this disease, which can have dramatic adverse effects on quality of life, is not uncommon, and can be difficult to treat, with about half of all patients failing to respond to standard therapy with high dose antihistamines. Alternate treatments used to treat the disease, including steroids and cyclosporine, can be effective, but can be highly toxic, he said.

"For refractory patients we have nothing that matches (omalizumab’s) combination of this kind of efficacy with low side effects, so many of us in the field kind of view this as a game changer for the patients," he said.

This study was sponsored by Genentech and Novartis Pharma. Several study authors made disclosures. A complete list of these disclosures is available with the full text of the article at NEJM.org.

fpnews@elsevier.com

SAN ANTONIO – Omalizumab diminished the signs and symptoms of chronic idiopathic urticaria in a dose-dependent fashion in a phase III study of 323 patients who failed to respond adequately to H1-antihistamines.

After 12 weeks of treatment with the recombinant humanized monoclonal antibody, improvements from baseline in weekly itch-severity scores were significantly greater in patients randomized to receive three doses of either 300 mg or 150 mg every 4 weeks, compared with placebo (score change of -9.8 and -8.1 vs. -5.1, respectively). The itch-severity score in patients randomized to receive a 75-mg dose changed by -5.9 points, but this did not differ significantly from the change in the placebo group, according to Dr. Marcus Maurer of Charite-Universitatsmedizin, Berlin. The report was published online on Feb. 24 in the New England Journal of Medicine.

The findings from this international double-blind trial were reported simultaneously at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In addition to meeting the primary 12-week response endpoint of change in weekly itch-severity score, patients receiving the 300-mg and 150-mg doses of omalizumab also experienced significant improvements, compared with patients given placebo, on all but one secondary endpoint, including change in the 7-day urticaria activity score (UAS7), change in the score for the weekly number of hives, time until a reduction from baseline of at least 5 points in the weekly itch-severity score (the MID), the proportions of patients with a UAS7 of 6 or less, the number of patients with a weekly MID response in the itch-severity score, the change from baseline in the score for the size of the largest hive, and change from baseline in the overall score on the Dermatology Life Quality Index. Those receiving 300 mg, but not those receiving 150 mg, also experienced significant improvement in the proportion of angioedema-free days from weeks 4-12 (N. Engl. J. Med. 2013 Feb. 24 [doi:10.1056/NEJMoa1215372]).

In a post hoc analysis at 12 weeks, 53%, 23%, 18%, and 10%, of those in the 300-mg, 150-mg, 75-mg, and placebo groups, respectively, were completely free of hives, and 44%, 22%, 16%, and 5%, respectively, were free of both hives and itching.

Of note, many patients experienced extremely rapid improvement, raising questions about a potential, as-yet unidentified and fundamental characteristic of this disease, study coauthors Dr. Thomas B. Casale, professor of medicine and medical microbiology and immunology and chief of allergy/immunology at Creighton University Medical Center, Omaha, Neb., and Dr. Allen P. Kaplan, clinical professor of medicine at the Medical University of South Carolina, Charleston, reported during a press briefing at AAAAI.

They explained that omalizumab, currently approved as an add-on therapy for moderate to severe persistent allergic asthma, is known to bind the allergic antibody immunoglobulin E (IgE). Many patients with chronic urticaria have an antibody that binds to a protein on the surface of histamine-containing cells, and that protein binds IgE.

"Just one injection drops one’s IgE level pretty close to zero ... and we learned that when we drop IgE to rock bottom, the protein on the cell to which it is attached also drops – and that’s the protein that the circulating antibody interacts with. The thinking was that if we drop the surface protein low enough, there’s nothing for the antibody to react with, and the hives would improve," he said.

This was, in fact, the case, as demonstrated in a phase I study of 12 patients, in which 7 patients responded dramatically, 4 responded partially, and 1 had no response. These findings led to the current phase III study, which is one of three such studies that investigators hope will lead to the drug’s approval for chronic idiopathic urticaria, because the high cost of the drug is prohibitive with respect to off-label use.

The same effect was seen in the current study.

This effect, however, takes a couple weeks to become apparent, so the rapid responses that occur in numerous patients suggest there is something more at play.

"This is working even faster than we thought, and probably there is a function of the allergic antibody that we do not yet understand," Dr. Kaplan said. "So this is going to be not only a terrific therapy for the disorder, but will lead to research in the future that probably – we hope – will elucidate the underlying abnormality of chronic urticaria beyond our current understanding of it. It’s very exciting, because it might elucidate some fundamental analogy that we don’t appreciate, and would have implications for allergic disease across the board."

The current study comprised patients aged 12-75 years who had a 6-month or longer history of chronic idiopathic urticaria, the presence of hives associated with itching for at least 8 consecutive weeks at any time prior to enrollment (despite H1-antihistamine use), a UAS7 of 16 or more during a 7-day period, a weekly itch-severity score of at least 8, a score of at least 4 on the UAS on at least one of the screening-visit days, and receipt of a licensed dose of a second-generation H1-antihistamine for at least 3 consecutive days immediately prior to the screening visit. Those with a clearly defined underlying cause for their symptoms were excluded. The doses evaluated in this study were based on a prior dose-ranging study, which showed no additional benefit with doses over 300 mg, the investigators said.

Patients continued to receive stable doses of H1-antihistamines throughout the 12-week treatment period, and were permitted to use diphenhydramine as a rescue medication.

Omalizumab was well tolerated in this study, with a similar number of adverse events occurring across the treatment groups. Serious adverse events occurred more often in the 300-mg group, with 6% of patients in that group experiencing a serious adverse event, compared with 3% of patients in the placebo group, and 1% of patients in the 150-mg and 75-mg groups, but the events were not considered to be related to the study drug.

The duration of response, however, was limited, as noted during a 16-week observation period following the initial 12-week treatment period.

Although the weekly itch-severity scores did not return to baseline during follow-up, they did increase to the levels seen in the placebo group.

The findings are nonetheless encouraging, Dr. Kaplan said, noting that this disease, which can have dramatic adverse effects on quality of life, is not uncommon, and can be difficult to treat, with about half of all patients failing to respond to standard therapy with high dose antihistamines. Alternate treatments used to treat the disease, including steroids and cyclosporine, can be effective, but can be highly toxic, he said.

"For refractory patients we have nothing that matches (omalizumab’s) combination of this kind of efficacy with low side effects, so many of us in the field kind of view this as a game changer for the patients," he said.

This study was sponsored by Genentech and Novartis Pharma. Several study authors made disclosures. A complete list of these disclosures is available with the full text of the article at NEJM.org.

fpnews@elsevier.com

SAN ANTONIO – Omalizumab diminished the signs and symptoms of chronic idiopathic urticaria in a dose-dependent fashion in a phase III study of 323 patients who failed to respond adequately to H1-antihistamines.

After 12 weeks of treatment with the recombinant humanized monoclonal antibody, improvements from baseline in weekly itch-severity scores were significantly greater in patients randomized to receive three doses of either 300 mg or 150 mg every 4 weeks, compared with placebo (score change of -9.8 and -8.1 vs. -5.1, respectively). The itch-severity score in patients randomized to receive a 75-mg dose changed by -5.9 points, but this did not differ significantly from the change in the placebo group, according to Dr. Marcus Maurer of Charite-Universitatsmedizin, Berlin. The report was published online on Feb. 24 in the New England Journal of Medicine.

The findings from this international double-blind trial were reported simultaneously at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In addition to meeting the primary 12-week response endpoint of change in weekly itch-severity score, patients receiving the 300-mg and 150-mg doses of omalizumab also experienced significant improvements, compared with patients given placebo, on all but one secondary endpoint, including change in the 7-day urticaria activity score (UAS7), change in the score for the weekly number of hives, time until a reduction from baseline of at least 5 points in the weekly itch-severity score (the MID), the proportions of patients with a UAS7 of 6 or less, the number of patients with a weekly MID response in the itch-severity score, the change from baseline in the score for the size of the largest hive, and change from baseline in the overall score on the Dermatology Life Quality Index. Those receiving 300 mg, but not those receiving 150 mg, also experienced significant improvement in the proportion of angioedema-free days from weeks 4-12 (N. Engl. J. Med. 2013 Feb. 24 [doi:10.1056/NEJMoa1215372]).

In a post hoc analysis at 12 weeks, 53%, 23%, 18%, and 10%, of those in the 300-mg, 150-mg, 75-mg, and placebo groups, respectively, were completely free of hives, and 44%, 22%, 16%, and 5%, respectively, were free of both hives and itching.

Of note, many patients experienced extremely rapid improvement, raising questions about a potential, as-yet unidentified and fundamental characteristic of this disease, study coauthors Dr. Thomas B. Casale, professor of medicine and medical microbiology and immunology and chief of allergy/immunology at Creighton University Medical Center, Omaha, Neb., and Dr. Allen P. Kaplan, clinical professor of medicine at the Medical University of South Carolina, Charleston, reported during a press briefing at AAAAI.

They explained that omalizumab, currently approved as an add-on therapy for moderate to severe persistent allergic asthma, is known to bind the allergic antibody immunoglobulin E (IgE). Many patients with chronic urticaria have an antibody that binds to a protein on the surface of histamine-containing cells, and that protein binds IgE.

"Just one injection drops one’s IgE level pretty close to zero ... and we learned that when we drop IgE to rock bottom, the protein on the cell to which it is attached also drops – and that’s the protein that the circulating antibody interacts with. The thinking was that if we drop the surface protein low enough, there’s nothing for the antibody to react with, and the hives would improve," he said.

This was, in fact, the case, as demonstrated in a phase I study of 12 patients, in which 7 patients responded dramatically, 4 responded partially, and 1 had no response. These findings led to the current phase III study, which is one of three such studies that investigators hope will lead to the drug’s approval for chronic idiopathic urticaria, because the high cost of the drug is prohibitive with respect to off-label use.

The same effect was seen in the current study.

This effect, however, takes a couple weeks to become apparent, so the rapid responses that occur in numerous patients suggest there is something more at play.

"This is working even faster than we thought, and probably there is a function of the allergic antibody that we do not yet understand," Dr. Kaplan said. "So this is going to be not only a terrific therapy for the disorder, but will lead to research in the future that probably – we hope – will elucidate the underlying abnormality of chronic urticaria beyond our current understanding of it. It’s very exciting, because it might elucidate some fundamental analogy that we don’t appreciate, and would have implications for allergic disease across the board."

The current study comprised patients aged 12-75 years who had a 6-month or longer history of chronic idiopathic urticaria, the presence of hives associated with itching for at least 8 consecutive weeks at any time prior to enrollment (despite H1-antihistamine use), a UAS7 of 16 or more during a 7-day period, a weekly itch-severity score of at least 8, a score of at least 4 on the UAS on at least one of the screening-visit days, and receipt of a licensed dose of a second-generation H1-antihistamine for at least 3 consecutive days immediately prior to the screening visit. Those with a clearly defined underlying cause for their symptoms were excluded. The doses evaluated in this study were based on a prior dose-ranging study, which showed no additional benefit with doses over 300 mg, the investigators said.

Patients continued to receive stable doses of H1-antihistamines throughout the 12-week treatment period, and were permitted to use diphenhydramine as a rescue medication.

Omalizumab was well tolerated in this study, with a similar number of adverse events occurring across the treatment groups. Serious adverse events occurred more often in the 300-mg group, with 6% of patients in that group experiencing a serious adverse event, compared with 3% of patients in the placebo group, and 1% of patients in the 150-mg and 75-mg groups, but the events were not considered to be related to the study drug.

The duration of response, however, was limited, as noted during a 16-week observation period following the initial 12-week treatment period.

Although the weekly itch-severity scores did not return to baseline during follow-up, they did increase to the levels seen in the placebo group.

The findings are nonetheless encouraging, Dr. Kaplan said, noting that this disease, which can have dramatic adverse effects on quality of life, is not uncommon, and can be difficult to treat, with about half of all patients failing to respond to standard therapy with high dose antihistamines. Alternate treatments used to treat the disease, including steroids and cyclosporine, can be effective, but can be highly toxic, he said.

"For refractory patients we have nothing that matches (omalizumab’s) combination of this kind of efficacy with low side effects, so many of us in the field kind of view this as a game changer for the patients," he said.

This study was sponsored by Genentech and Novartis Pharma. Several study authors made disclosures. A complete list of these disclosures is available with the full text of the article at NEJM.org.

fpnews@elsevier.com