Eczema Therapy Response Varies by Filaggrin Mutation

RALEIGH, N.C. – Atopic dermatitis patients who possess a filaggrin loss-of-function mutation are not likely to be clear of the skin disease for longer than 5 months at a time, according to study results.

The prospective cohort PEER (Pediatric Eczema Elective Registry) study also found that the four most prevalent filaggrin mutations in white patients do not respond similarly to atopic dermatitis medications.

For example, patients with at least one null allele for R501X – the most prevalent filaggrin mutation in the PEER cohort – were 55% less likely than the group as a whole to report being symptom free for 6 months while off all medications for atopic dermatitis. In contrast, those with an S3247X mutation were 3.7-fold more likely to be both symptom and medication free for a 6-month period, according to Dr. David J. Margolis, professor of dermatology at the University of Pennsylvania, Philadelphia.

He presented a study involving 857 PEER participants who underwent DNA analysis screening for the four most common filaggrin mutations in white patients (R501X, 2282del4, R2247X, and S3247X). A total of 28% of white patients had at least one of the mutations, as did 5% of black patients. An R501X mutation was present in 12.2% of white patients and 3.3% of black patients. The second most common mutation (2282del4) was noted in 11.8% of white patients and 0.6% of black patients.

The ongoing Valeant Pharmaceutical–funded PEER study involves children with atopic dermatitis who used topical pimecrolimus (Elidel) for at least 6 weeks during the 6 months immediately prior to enrollment. Their average age at diagnosis was 2.1 years. Participants have been prospectively followed in the registry for a mean of roughly 5 years. They can use any form of treatment they choose. Data on the status of their skin disease are collected at 6-month intervals, allowing for the characteristic waxing and waning of atopic dermatitis.

In all, 81% of PEER participants have been symptom free for at least 6 months on at least one occasion during the 5 years of follow-up. However, only 25.6% were both symptom free and not using an eczema medication.

In a cross-sectional snapshot obtained at 3 years of follow-up, 62% of patients were still using a topical calcineurin inhibitor, 58% were on topical steroids, and 35% were on both forms of therapy.

Patients with any of the four filaggrin mutations were 50% as likely as those without a mutation to be symptom free for a 6-month period, after adjustment for age, sex, and ancestry.

Participants with an R501X mutation were an adjusted 55% less likely than the overall PEER cohort to be symptom free for 6 months while off medications; hence, they could be said to have significantly more persistent or severe disease, Dr. Margolis noted.

In contrast, patients with a 2282del4 mutation were 1.7-fold more likely than the overall group to be symptom free while off therapy for 6 months, whereas those with an R2247X mutation were about equally likely as the patients with none of the filaggrin mutations to enjoy such a period.

The filaggrin gene, which is located on chromosome 1, codes for filament-aggregating protein. It is thought that filaggrin loss-of-function mutations promote breakdown of the skin barrier, allowing a more aggressive immunologic response to antigens and irritants. In 2006, it was demonstrated that filaggrin loss-of-function mutations increase an individual’s risk of developing atopic dermatitis threefold.

That being said, the PEER analysis demonstrates that different filaggrin mutations vary considerably in the degree to which their associated skin disease is treatment-refractory. One reasonable hypothesis is that these differences in treatment responsiveness are related to mutation penetrance.

A limitation of this PEER analysis is that it screened only for the four most prevalent filaggrin mutations, he noted. Roughly 30-40 mutations have been reported thus far.

This study was funded by the National Institutes of Health. Dr. Margolis reported having no financial conflicts.

RALEIGH, N.C. – Atopic dermatitis patients who possess a filaggrin loss-of-function mutation are not likely to be clear of the skin disease for longer than 5 months at a time, according to study results.

The prospective cohort PEER (Pediatric Eczema Elective Registry) study also found that the four most prevalent filaggrin mutations in white patients do not respond similarly to atopic dermatitis medications.

For example, patients with at least one null allele for R501X – the most prevalent filaggrin mutation in the PEER cohort – were 55% less likely than the group as a whole to report being symptom free for 6 months while off all medications for atopic dermatitis. In contrast, those with an S3247X mutation were 3.7-fold more likely to be both symptom and medication free for a 6-month period, according to Dr. David J. Margolis, professor of dermatology at the University of Pennsylvania, Philadelphia.

He presented a study involving 857 PEER participants who underwent DNA analysis screening for the four most common filaggrin mutations in white patients (R501X, 2282del4, R2247X, and S3247X). A total of 28% of white patients had at least one of the mutations, as did 5% of black patients. An R501X mutation was present in 12.2% of white patients and 3.3% of black patients. The second most common mutation (2282del4) was noted in 11.8% of white patients and 0.6% of black patients.

The ongoing Valeant Pharmaceutical–funded PEER study involves children with atopic dermatitis who used topical pimecrolimus (Elidel) for at least 6 weeks during the 6 months immediately prior to enrollment. Their average age at diagnosis was 2.1 years. Participants have been prospectively followed in the registry for a mean of roughly 5 years. They can use any form of treatment they choose. Data on the status of their skin disease are collected at 6-month intervals, allowing for the characteristic waxing and waning of atopic dermatitis.

In all, 81% of PEER participants have been symptom free for at least 6 months on at least one occasion during the 5 years of follow-up. However, only 25.6% were both symptom free and not using an eczema medication.

In a cross-sectional snapshot obtained at 3 years of follow-up, 62% of patients were still using a topical calcineurin inhibitor, 58% were on topical steroids, and 35% were on both forms of therapy.

Patients with any of the four filaggrin mutations were 50% as likely as those without a mutation to be symptom free for a 6-month period, after adjustment for age, sex, and ancestry.

Participants with an R501X mutation were an adjusted 55% less likely than the overall PEER cohort to be symptom free for 6 months while off medications; hence, they could be said to have significantly more persistent or severe disease, Dr. Margolis noted.

In contrast, patients with a 2282del4 mutation were 1.7-fold more likely than the overall group to be symptom free while off therapy for 6 months, whereas those with an R2247X mutation were about equally likely as the patients with none of the filaggrin mutations to enjoy such a period.

The filaggrin gene, which is located on chromosome 1, codes for filament-aggregating protein. It is thought that filaggrin loss-of-function mutations promote breakdown of the skin barrier, allowing a more aggressive immunologic response to antigens and irritants. In 2006, it was demonstrated that filaggrin loss-of-function mutations increase an individual’s risk of developing atopic dermatitis threefold.

That being said, the PEER analysis demonstrates that different filaggrin mutations vary considerably in the degree to which their associated skin disease is treatment-refractory. One reasonable hypothesis is that these differences in treatment responsiveness are related to mutation penetrance.

A limitation of this PEER analysis is that it screened only for the four most prevalent filaggrin mutations, he noted. Roughly 30-40 mutations have been reported thus far.

This study was funded by the National Institutes of Health. Dr. Margolis reported having no financial conflicts.

RALEIGH, N.C. – Atopic dermatitis patients who possess a filaggrin loss-of-function mutation are not likely to be clear of the skin disease for longer than 5 months at a time, according to study results.

The prospective cohort PEER (Pediatric Eczema Elective Registry) study also found that the four most prevalent filaggrin mutations in white patients do not respond similarly to atopic dermatitis medications.

For example, patients with at least one null allele for R501X – the most prevalent filaggrin mutation in the PEER cohort – were 55% less likely than the group as a whole to report being symptom free for 6 months while off all medications for atopic dermatitis. In contrast, those with an S3247X mutation were 3.7-fold more likely to be both symptom and medication free for a 6-month period, according to Dr. David J. Margolis, professor of dermatology at the University of Pennsylvania, Philadelphia.

He presented a study involving 857 PEER participants who underwent DNA analysis screening for the four most common filaggrin mutations in white patients (R501X, 2282del4, R2247X, and S3247X). A total of 28% of white patients had at least one of the mutations, as did 5% of black patients. An R501X mutation was present in 12.2% of white patients and 3.3% of black patients. The second most common mutation (2282del4) was noted in 11.8% of white patients and 0.6% of black patients.

The ongoing Valeant Pharmaceutical–funded PEER study involves children with atopic dermatitis who used topical pimecrolimus (Elidel) for at least 6 weeks during the 6 months immediately prior to enrollment. Their average age at diagnosis was 2.1 years. Participants have been prospectively followed in the registry for a mean of roughly 5 years. They can use any form of treatment they choose. Data on the status of their skin disease are collected at 6-month intervals, allowing for the characteristic waxing and waning of atopic dermatitis.

In all, 81% of PEER participants have been symptom free for at least 6 months on at least one occasion during the 5 years of follow-up. However, only 25.6% were both symptom free and not using an eczema medication.

In a cross-sectional snapshot obtained at 3 years of follow-up, 62% of patients were still using a topical calcineurin inhibitor, 58% were on topical steroids, and 35% were on both forms of therapy.

Patients with any of the four filaggrin mutations were 50% as likely as those without a mutation to be symptom free for a 6-month period, after adjustment for age, sex, and ancestry.

Participants with an R501X mutation were an adjusted 55% less likely than the overall PEER cohort to be symptom free for 6 months while off medications; hence, they could be said to have significantly more persistent or severe disease, Dr. Margolis noted.

In contrast, patients with a 2282del4 mutation were 1.7-fold more likely than the overall group to be symptom free while off therapy for 6 months, whereas those with an R2247X mutation were about equally likely as the patients with none of the filaggrin mutations to enjoy such a period.

The filaggrin gene, which is located on chromosome 1, codes for filament-aggregating protein. It is thought that filaggrin loss-of-function mutations promote breakdown of the skin barrier, allowing a more aggressive immunologic response to antigens and irritants. In 2006, it was demonstrated that filaggrin loss-of-function mutations increase an individual’s risk of developing atopic dermatitis threefold.

That being said, the PEER analysis demonstrates that different filaggrin mutations vary considerably in the degree to which their associated skin disease is treatment-refractory. One reasonable hypothesis is that these differences in treatment responsiveness are related to mutation penetrance.

A limitation of this PEER analysis is that it screened only for the four most prevalent filaggrin mutations, he noted. Roughly 30-40 mutations have been reported thus far.

This study was funded by the National Institutes of Health. Dr. Margolis reported having no financial conflicts.