Atopic Dermatitis

SAN DIEGO – The oral opioid nalbuphine was safe and significantly reduced itching intensity in hemodialysis patients with uremic pruritus, a randomized, placebo-controlled trial showed.

“Uremic pruritus is a common problem in dialysis patients,” Dr. Vandana S. Mathur said during a press briefing at a meeting sponsored by the American Society of Nephrology. “A recent study in over 73,000 patients found that 60% of them experience pruritus, and 30% of them experience moderate to severe pruritus. Uremic pruritus is associated with worsening quality of life, sleep, mood, social functioning, higher use of IV antibiotics, higher erythropoiesis-stimulating agent and iron doses, and higher mortality.”

Endogenous opioids are important in the pathogenesis of itch, including itch related to systemic disease, noted Dr. Mathur, a nephrologist and clinical and regulatory drug development consultant based in Woodside, Calif.

“Mu receptors mediate mast cell degranulation and have direct central and peripheral pruritogenic effects, while kappa receptors mediate opposing, antipruritic effects,” she said. “Hemodialysis patients have an increased ratio of beta-endorphin to dynorphin A, and the ratio is associated with increased itch intensity.”

Extended-release nalbuphine is a mu receptor antagonist and a kappa receptor agonist being developed by Trevi Therapeutics. “This dual mechanism of action suggests that it may be effective in the treatment of uremic pruritus,” Dr. Mathur said.

The researchers enrolled 373 hemodialysis patients at 46 sites who had moderate or severe uremic pruritus in a phase II/III study. The primary objectives were to evaluate the drug’s effects on itching intensity as assessed by the Worst Itching Numerical Rating Scale (NRS), as well as safety and tolerability. The patients were randomized 1:1:1 to nalbuphine 60 mg b.i.d., nalbuphine 120 mg b.i.d., or placebo b.i.d. for 8 weeks.

Patients’ mean age was 55 years, and 57% were male. They had been on hemodialysis for nearly 5 years and had experienced pruritus for an average of 3.2 years.

The mean NRS in the 120-mg nalbuphine group declined by 3.5 (from 6.9) on the 10-point scale, which represented a 49% decrease in symptoms and was statistically significant from the least squares mean NRS observed in the placebo group (P = .017), Dr. Mathur reported.

The mean NRS in the 60-mg nalbuphine group declined by 3.1 (from 6.9), which was not statistically different from the least squares mean NRS in the placebo group (P = .432).

“The effect of 120-mg nalbuphine b.i.d. was evident within 1 week following titration and was durable for the full 8-week treatment period,” Dr. Mathur said.

The most common adverse events resulting in discontinuation were nausea, vomiting, somnolence, dizziness, and hallucination, with the incidence rate of these events quickly approaching that of placebo after the first week of titration.

The study’s secondary endpoints of itch-related quality of life and sleep were not significantly improved, “but directional trends supported the primary endpoint findings,” she said.

Trevi Therapeutics supported the study. Dr. Mathur disclosed that she is a consultant for the company.

dbrunk@frontlinemedcom.com

SAN DIEGO – The oral opioid nalbuphine was safe and significantly reduced itching intensity in hemodialysis patients with uremic pruritus, a randomized, placebo-controlled trial showed.

“Uremic pruritus is a common problem in dialysis patients,” Dr. Vandana S. Mathur said during a press briefing at a meeting sponsored by the American Society of Nephrology. “A recent study in over 73,000 patients found that 60% of them experience pruritus, and 30% of them experience moderate to severe pruritus. Uremic pruritus is associated with worsening quality of life, sleep, mood, social functioning, higher use of IV antibiotics, higher erythropoiesis-stimulating agent and iron doses, and higher mortality.”

Endogenous opioids are important in the pathogenesis of itch, including itch related to systemic disease, noted Dr. Mathur, a nephrologist and clinical and regulatory drug development consultant based in Woodside, Calif.

“Mu receptors mediate mast cell degranulation and have direct central and peripheral pruritogenic effects, while kappa receptors mediate opposing, antipruritic effects,” she said. “Hemodialysis patients have an increased ratio of beta-endorphin to dynorphin A, and the ratio is associated with increased itch intensity.”

Extended-release nalbuphine is a mu receptor antagonist and a kappa receptor agonist being developed by Trevi Therapeutics. “This dual mechanism of action suggests that it may be effective in the treatment of uremic pruritus,” Dr. Mathur said.

The researchers enrolled 373 hemodialysis patients at 46 sites who had moderate or severe uremic pruritus in a phase II/III study. The primary objectives were to evaluate the drug’s effects on itching intensity as assessed by the Worst Itching Numerical Rating Scale (NRS), as well as safety and tolerability. The patients were randomized 1:1:1 to nalbuphine 60 mg b.i.d., nalbuphine 120 mg b.i.d., or placebo b.i.d. for 8 weeks.

Patients’ mean age was 55 years, and 57% were male. They had been on hemodialysis for nearly 5 years and had experienced pruritus for an average of 3.2 years.

The mean NRS in the 120-mg nalbuphine group declined by 3.5 (from 6.9) on the 10-point scale, which represented a 49% decrease in symptoms and was statistically significant from the least squares mean NRS observed in the placebo group (P = .017), Dr. Mathur reported.

The mean NRS in the 60-mg nalbuphine group declined by 3.1 (from 6.9), which was not statistically different from the least squares mean NRS in the placebo group (P = .432).

“The effect of 120-mg nalbuphine b.i.d. was evident within 1 week following titration and was durable for the full 8-week treatment period,” Dr. Mathur said.

The most common adverse events resulting in discontinuation were nausea, vomiting, somnolence, dizziness, and hallucination, with the incidence rate of these events quickly approaching that of placebo after the first week of titration.

The study’s secondary endpoints of itch-related quality of life and sleep were not significantly improved, “but directional trends supported the primary endpoint findings,” she said.

Trevi Therapeutics supported the study. Dr. Mathur disclosed that she is a consultant for the company.

dbrunk@frontlinemedcom.com

SAN DIEGO – The oral opioid nalbuphine was safe and significantly reduced itching intensity in hemodialysis patients with uremic pruritus, a randomized, placebo-controlled trial showed.

“Uremic pruritus is a common problem in dialysis patients,” Dr. Vandana S. Mathur said during a press briefing at a meeting sponsored by the American Society of Nephrology. “A recent study in over 73,000 patients found that 60% of them experience pruritus, and 30% of them experience moderate to severe pruritus. Uremic pruritus is associated with worsening quality of life, sleep, mood, social functioning, higher use of IV antibiotics, higher erythropoiesis-stimulating agent and iron doses, and higher mortality.”

Endogenous opioids are important in the pathogenesis of itch, including itch related to systemic disease, noted Dr. Mathur, a nephrologist and clinical and regulatory drug development consultant based in Woodside, Calif.

“Mu receptors mediate mast cell degranulation and have direct central and peripheral pruritogenic effects, while kappa receptors mediate opposing, antipruritic effects,” she said. “Hemodialysis patients have an increased ratio of beta-endorphin to dynorphin A, and the ratio is associated with increased itch intensity.”

Extended-release nalbuphine is a mu receptor antagonist and a kappa receptor agonist being developed by Trevi Therapeutics. “This dual mechanism of action suggests that it may be effective in the treatment of uremic pruritus,” Dr. Mathur said.

The researchers enrolled 373 hemodialysis patients at 46 sites who had moderate or severe uremic pruritus in a phase II/III study. The primary objectives were to evaluate the drug’s effects on itching intensity as assessed by the Worst Itching Numerical Rating Scale (NRS), as well as safety and tolerability. The patients were randomized 1:1:1 to nalbuphine 60 mg b.i.d., nalbuphine 120 mg b.i.d., or placebo b.i.d. for 8 weeks.

Patients’ mean age was 55 years, and 57% were male. They had been on hemodialysis for nearly 5 years and had experienced pruritus for an average of 3.2 years.

The mean NRS in the 120-mg nalbuphine group declined by 3.5 (from 6.9) on the 10-point scale, which represented a 49% decrease in symptoms and was statistically significant from the least squares mean NRS observed in the placebo group (P = .017), Dr. Mathur reported.

The mean NRS in the 60-mg nalbuphine group declined by 3.1 (from 6.9), which was not statistically different from the least squares mean NRS in the placebo group (P = .432).

“The effect of 120-mg nalbuphine b.i.d. was evident within 1 week following titration and was durable for the full 8-week treatment period,” Dr. Mathur said.

The most common adverse events resulting in discontinuation were nausea, vomiting, somnolence, dizziness, and hallucination, with the incidence rate of these events quickly approaching that of placebo after the first week of titration.

The study’s secondary endpoints of itch-related quality of life and sleep were not significantly improved, “but directional trends supported the primary endpoint findings,” she said.

Trevi Therapeutics supported the study. Dr. Mathur disclosed that she is a consultant for the company.

dbrunk@frontlinemedcom.com

Atopic dermatitis (AD) is a chronic inflammatory skin disease that typically begins in early childhood (Figure). It is one of the most commonly diagnosed dermatologic conditions, affecting up to 25% of children and 2% to 3% of adults in the United States.^1,2 The mainstays of treatment for AD are topical emollients and topical medications, of which corticosteroids are most commonly prescribed.³ Although treatments for AD generally are straightforward and efficacious when used correctly, poor adherence to treatment often prevents patients from achieving disease control.⁴ Patient adherence to therapy is a familiar challenge in dermatology, especially for diseases like AD that require long-term treatment with topical medications.^4,5 In some instances, poor adherence may be misconstrued as poor response to treatment, which may lead to escalation to more powerful and potentially dangerous systemic medications.⁶ Ensuring good adherence to treatment leads to better outcomes and disease control, averts unnecessary treatment, prevents disease complications, improves quality of life, and decreases treatment cost.^4,5 This article provides a review of the literature on patient adherence to topical therapies for AD as well as a discussion of methods to improve patient adherence to treatment in the clinical setting.

Methods

A PubMed search of articles indexed for MEDLINE from January 2005 to May 2015 was conducted to identify studies that focused on treatment adherence in AD using the search terms atopic dermatitis and medication adherence and atopic dermatitis and patient compliance After excluding duplicate results and those that were not in the English language, a final list of clinical trials that investigated patient adherence/compliance to topical medications for the treatment of AD was extracted for evaluation.

Results

Our review of the literature yielded 7 quantitative studies that evaluated adherence to topical medications in AD using electronic monitoring and/or self-reporting (Table).^7-13 Participant demographics, disease severity, drug and vehicle used, duration of treatment, and number of follow-up visits varied. All studies used medication event monitoring system caps on medication jars to objectively track patient adherence by recording the date and time when the cap was removed. To assess disease response, the studies used such measures as the Investigator Global Assessment scale, Eczema Area and Severity Index score, or other visual analog scales.

In all of the studies, treatment proved effective and disease severity declined from baseline regardless of the rate of adherence, with benefit continuing after treatment had ended.^7-13 Some results suggested that better adherence increased treatment efficacy and reduced disease severity.^8,9 However, one 10-day trial found no difference in severity and efficacy among participants who applied the medication at least once daily, missed applications some days, or applied the medication more than twice daily.¹³

Study participants typically overestimated their adherence to treatment compared to actual adherence rates, with most reporting near 100% adherence.^7-9,11,12 Average measured adherence rates ranged from 32% to 93% (Table). Adherence rates typically were highest at the beginning of the study and decreased as the study continued.^7-13 The study with the best average adherence rate of 93% had the shortest treatment period of 3 days,¹¹ and the study with the lowest average adherence rate of 32% had the longest treatment period of 8 weeks.⁷ The study with the lowest adherence rate was the only study wherein participants were blinded to their enrollment in the study, which would most closely mimic adherence rates in clinical practice.⁷ The participants in the other studies were not aware that their adherence was being monitored, but their behavior may have been influenced since they were aware of their enrollment in the study.

Many variables affect treatment adherence in patients with AD. Average adherence rates were significantly higher (P=.03) in participants with greater disease severity.⁷ There is conflicting evidence regarding the role of medication vehicle in treatment adherence. While Wilson et al⁹ did not find any difference in adherence based on medication vehicle, Yentzer et al¹² found vehicle characteristics and medication side effects were among patients’ top-ranked concerns about using topical medications. Sagransky et al¹⁰ compared treatment adherence between 2 groups of AD patients: one control group received a standard-of-care 4-week follow-up, and an active group received an additional 1-week follow-up. The mean adherence rate of the treatment group was 69% compared with 54% in the control group.¹⁰

Comment

Poor adherence to treatment is a pervasive problem in patients with AD. Our review of the literature confirmed that patients generally are not accurate historians of their medication usage, often reporting near-perfect treatment adherence even when actual adherence is poor. Rates of adherence from clinical trials are likely higher than those seen in clinical practice due in part to study incentives and differences between how patients in a study are treated compared to those in a physician’s clinic; for example, research study participants often have additional follow-up visits compared to those being treated in the clinical population and by virtue of being enrolled in a study are aware that their behavior is being monitored, which can increase treatment adherence.⁷

The dogma suggesting that tachyphylaxis can occur with long-term use of topical corticosteroids is not supported by clinical trials.¹⁴ Furthermore, in our review of the literature patient adherence was highest in the shortest study¹¹ and lowest in the longest study.⁷ Given that AD patients cannot benefit from a treatment if they do not use it, the supposed decrease in efficacy of topical corticosteroids over time may be because patients fail to use them consistently.

Our review of the literature was limited by the small body of research that exists on treatment adherence in AD patients, especially relating to topical medications, and did not reveal any studies evaluating systemic medications in AD. Of the studies we examined, sample sizes were small and treatment and follow-up periods were short. Our review only covered adherence to prescribed topical medications in AD, chiefly corticosteroids; thus, we did not evaluate adherence to other therapies (eg, emollients) in this patient population.

The existing research also is limited by the relative paucity of data showing a correlation between improved adherence to topical treatment and improved disease outcomes, which may be due to the methodological limitations of the study designs that have been used; for instance, studies may use objective monitors to describe daily adherence to treatment, but disease severity typically is measured over longer periods of time, usually every few weeks or months. Short-term data may not be an accurate demonstration of how participants’ actual treatment adherence impacts disease outcome, as the data does not account for more complex adherence factors; for example, participants who achieve good disease control using topical corticosteroids for an 8-week study period may actually demonstrate poor treatment adherence overall, as topical corticosteroids have good short-term efficacy and the patient may have stopped using the product after the first few weeks of the treatment period. In contrast, poorly adherent patients may never use the medication well enough to achieve improvement and may continue low-level use throughout the study period. Therefore, studies that measure disease severity at more regular intervals are required to show the true effect of treatment adherence on disease outcomes.

Since AD mainly affects children, family issues can pose special challenges to attaining good treatment adherence.^15,16 The physician–patient (or parent) relationship and the family’s perception of the patient’s disease severity are strong predictors of adherence to topical treatment.¹⁶ Potential barriers to adherence in the pediatric population are caregivers with negative beliefs about treatment, the time-consuming nature of applying topical therapies, or a child who is uncooperative.^15,17 In the treatment of infants, critical factors are caregiver availability and beliefs and fears about medications and their side effects, while in the teenage population, the desire to “fit in” and oppositional behavior can lead to poor adherence to treatment.¹⁷ Regardless of age, other barriers to treatment adherence are forgetfulness, belief that the drug is not working, and the messiness of treatment.¹⁷

Educational tools (eg, action plans, instructions about how to apply topical medications correctly) may be underutilized in patients with AD. If consistently implemented, these tools could have a positive impact on adherence to medication in patients with AD. For example, written action plans pioneered in the asthma community have shown to improve quality of life and reduce disease severity and may offer the same benefits for AD patients due to the similarities of the diseases.¹⁸ Since AD patients and their caregivers often are not well versed in how to apply topical medications correctly, efforts to educate patients could potentially increase adherence to treatment. In one study, AD patients began to use medications more effectively after applying a fluorescent cream to reveal affected areas they had missed, and clinicians were able to provide additional instruction based on the findings.¹⁹

Adherence to topical treatments among AD patients is a multifactorial issue. Regimens often are complex and inconvenient due to the need for multiple medications, the topical nature of the products, and the need for frequent application. To optimize prescription treatments, patients also must be diligent with preventive measures such as application of topical emollients and use of bathing techniques (eg, bleach baths). A way to overcome treatment complexity and increase adherence may be to provide a written action plan and involve the patient and caregiver in the plan’s development. If a drug formulation is not aesthetically acceptable to the patient (eg, the greasiness of an ointment), allowing the patient to choose the medication vehicle may increase satisfaction and use.¹² Fear of steroid side effects also is common among patients and caregivers and could be overcome with education about the product.²⁰

Conclusion

Treatment adherence can have a dramatic effect on diseases outcomes and can be particularly challenging in AD due to the use of topical medications with complex treatment regimens. Additionally, a large majority of patients with AD are children, from infants to teenagers, adding another layer of treatment challenges. Further research is needed to more definitively develop effective methods for enhancing treatment adherence in this patient population. Although enormous amounts of money are being spent to develop improved treatments for AD, we may be able to achieve far more benefit at a much lower cost by figuring out how to get patients to adhere to the treatments that are already available.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that typically begins in early childhood (Figure). It is one of the most commonly diagnosed dermatologic conditions, affecting up to 25% of children and 2% to 3% of adults in the United States.^1,2 The mainstays of treatment for AD are topical emollients and topical medications, of which corticosteroids are most commonly prescribed.³ Although treatments for AD generally are straightforward and efficacious when used correctly, poor adherence to treatment often prevents patients from achieving disease control.⁴ Patient adherence to therapy is a familiar challenge in dermatology, especially for diseases like AD that require long-term treatment with topical medications.^4,5 In some instances, poor adherence may be misconstrued as poor response to treatment, which may lead to escalation to more powerful and potentially dangerous systemic medications.⁶ Ensuring good adherence to treatment leads to better outcomes and disease control, averts unnecessary treatment, prevents disease complications, improves quality of life, and decreases treatment cost.^4,5 This article provides a review of the literature on patient adherence to topical therapies for AD as well as a discussion of methods to improve patient adherence to treatment in the clinical setting.

Methods

A PubMed search of articles indexed for MEDLINE from January 2005 to May 2015 was conducted to identify studies that focused on treatment adherence in AD using the search terms atopic dermatitis and medication adherence and atopic dermatitis and patient compliance After excluding duplicate results and those that were not in the English language, a final list of clinical trials that investigated patient adherence/compliance to topical medications for the treatment of AD was extracted for evaluation.

Results

Our review of the literature yielded 7 quantitative studies that evaluated adherence to topical medications in AD using electronic monitoring and/or self-reporting (Table).^7-13 Participant demographics, disease severity, drug and vehicle used, duration of treatment, and number of follow-up visits varied. All studies used medication event monitoring system caps on medication jars to objectively track patient adherence by recording the date and time when the cap was removed. To assess disease response, the studies used such measures as the Investigator Global Assessment scale, Eczema Area and Severity Index score, or other visual analog scales.

In all of the studies, treatment proved effective and disease severity declined from baseline regardless of the rate of adherence, with benefit continuing after treatment had ended.^7-13 Some results suggested that better adherence increased treatment efficacy and reduced disease severity.^8,9 However, one 10-day trial found no difference in severity and efficacy among participants who applied the medication at least once daily, missed applications some days, or applied the medication more than twice daily.¹³

Study participants typically overestimated their adherence to treatment compared to actual adherence rates, with most reporting near 100% adherence.^7-9,11,12 Average measured adherence rates ranged from 32% to 93% (Table). Adherence rates typically were highest at the beginning of the study and decreased as the study continued.^7-13 The study with the best average adherence rate of 93% had the shortest treatment period of 3 days,¹¹ and the study with the lowest average adherence rate of 32% had the longest treatment period of 8 weeks.⁷ The study with the lowest adherence rate was the only study wherein participants were blinded to their enrollment in the study, which would most closely mimic adherence rates in clinical practice.⁷ The participants in the other studies were not aware that their adherence was being monitored, but their behavior may have been influenced since they were aware of their enrollment in the study.

Many variables affect treatment adherence in patients with AD. Average adherence rates were significantly higher (P=.03) in participants with greater disease severity.⁷ There is conflicting evidence regarding the role of medication vehicle in treatment adherence. While Wilson et al⁹ did not find any difference in adherence based on medication vehicle, Yentzer et al¹² found vehicle characteristics and medication side effects were among patients’ top-ranked concerns about using topical medications. Sagransky et al¹⁰ compared treatment adherence between 2 groups of AD patients: one control group received a standard-of-care 4-week follow-up, and an active group received an additional 1-week follow-up. The mean adherence rate of the treatment group was 69% compared with 54% in the control group.¹⁰

Comment

Poor adherence to treatment is a pervasive problem in patients with AD. Our review of the literature confirmed that patients generally are not accurate historians of their medication usage, often reporting near-perfect treatment adherence even when actual adherence is poor. Rates of adherence from clinical trials are likely higher than those seen in clinical practice due in part to study incentives and differences between how patients in a study are treated compared to those in a physician’s clinic; for example, research study participants often have additional follow-up visits compared to those being treated in the clinical population and by virtue of being enrolled in a study are aware that their behavior is being monitored, which can increase treatment adherence.⁷

The dogma suggesting that tachyphylaxis can occur with long-term use of topical corticosteroids is not supported by clinical trials.¹⁴ Furthermore, in our review of the literature patient adherence was highest in the shortest study¹¹ and lowest in the longest study.⁷ Given that AD patients cannot benefit from a treatment if they do not use it, the supposed decrease in efficacy of topical corticosteroids over time may be because patients fail to use them consistently.

Our review of the literature was limited by the small body of research that exists on treatment adherence in AD patients, especially relating to topical medications, and did not reveal any studies evaluating systemic medications in AD. Of the studies we examined, sample sizes were small and treatment and follow-up periods were short. Our review only covered adherence to prescribed topical medications in AD, chiefly corticosteroids; thus, we did not evaluate adherence to other therapies (eg, emollients) in this patient population.

The existing research also is limited by the relative paucity of data showing a correlation between improved adherence to topical treatment and improved disease outcomes, which may be due to the methodological limitations of the study designs that have been used; for instance, studies may use objective monitors to describe daily adherence to treatment, but disease severity typically is measured over longer periods of time, usually every few weeks or months. Short-term data may not be an accurate demonstration of how participants’ actual treatment adherence impacts disease outcome, as the data does not account for more complex adherence factors; for example, participants who achieve good disease control using topical corticosteroids for an 8-week study period may actually demonstrate poor treatment adherence overall, as topical corticosteroids have good short-term efficacy and the patient may have stopped using the product after the first few weeks of the treatment period. In contrast, poorly adherent patients may never use the medication well enough to achieve improvement and may continue low-level use throughout the study period. Therefore, studies that measure disease severity at more regular intervals are required to show the true effect of treatment adherence on disease outcomes.

Since AD mainly affects children, family issues can pose special challenges to attaining good treatment adherence.^15,16 The physician–patient (or parent) relationship and the family’s perception of the patient’s disease severity are strong predictors of adherence to topical treatment.¹⁶ Potential barriers to adherence in the pediatric population are caregivers with negative beliefs about treatment, the time-consuming nature of applying topical therapies, or a child who is uncooperative.^15,17 In the treatment of infants, critical factors are caregiver availability and beliefs and fears about medications and their side effects, while in the teenage population, the desire to “fit in” and oppositional behavior can lead to poor adherence to treatment.¹⁷ Regardless of age, other barriers to treatment adherence are forgetfulness, belief that the drug is not working, and the messiness of treatment.¹⁷

Educational tools (eg, action plans, instructions about how to apply topical medications correctly) may be underutilized in patients with AD. If consistently implemented, these tools could have a positive impact on adherence to medication in patients with AD. For example, written action plans pioneered in the asthma community have shown to improve quality of life and reduce disease severity and may offer the same benefits for AD patients due to the similarities of the diseases.¹⁸ Since AD patients and their caregivers often are not well versed in how to apply topical medications correctly, efforts to educate patients could potentially increase adherence to treatment. In one study, AD patients began to use medications more effectively after applying a fluorescent cream to reveal affected areas they had missed, and clinicians were able to provide additional instruction based on the findings.¹⁹

Adherence to topical treatments among AD patients is a multifactorial issue. Regimens often are complex and inconvenient due to the need for multiple medications, the topical nature of the products, and the need for frequent application. To optimize prescription treatments, patients also must be diligent with preventive measures such as application of topical emollients and use of bathing techniques (eg, bleach baths). A way to overcome treatment complexity and increase adherence may be to provide a written action plan and involve the patient and caregiver in the plan’s development. If a drug formulation is not aesthetically acceptable to the patient (eg, the greasiness of an ointment), allowing the patient to choose the medication vehicle may increase satisfaction and use.¹² Fear of steroid side effects also is common among patients and caregivers and could be overcome with education about the product.²⁰

Conclusion

Treatment adherence can have a dramatic effect on diseases outcomes and can be particularly challenging in AD due to the use of topical medications with complex treatment regimens. Additionally, a large majority of patients with AD are children, from infants to teenagers, adding another layer of treatment challenges. Further research is needed to more definitively develop effective methods for enhancing treatment adherence in this patient population. Although enormous amounts of money are being spent to develop improved treatments for AD, we may be able to achieve far more benefit at a much lower cost by figuring out how to get patients to adhere to the treatments that are already available.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that typically begins in early childhood (Figure). It is one of the most commonly diagnosed dermatologic conditions, affecting up to 25% of children and 2% to 3% of adults in the United States.^1,2 The mainstays of treatment for AD are topical emollients and topical medications, of which corticosteroids are most commonly prescribed.³ Although treatments for AD generally are straightforward and efficacious when used correctly, poor adherence to treatment often prevents patients from achieving disease control.⁴ Patient adherence to therapy is a familiar challenge in dermatology, especially for diseases like AD that require long-term treatment with topical medications.^4,5 In some instances, poor adherence may be misconstrued as poor response to treatment, which may lead to escalation to more powerful and potentially dangerous systemic medications.⁶ Ensuring good adherence to treatment leads to better outcomes and disease control, averts unnecessary treatment, prevents disease complications, improves quality of life, and decreases treatment cost.^4,5 This article provides a review of the literature on patient adherence to topical therapies for AD as well as a discussion of methods to improve patient adherence to treatment in the clinical setting.

Methods

A PubMed search of articles indexed for MEDLINE from January 2005 to May 2015 was conducted to identify studies that focused on treatment adherence in AD using the search terms atopic dermatitis and medication adherence and atopic dermatitis and patient compliance After excluding duplicate results and those that were not in the English language, a final list of clinical trials that investigated patient adherence/compliance to topical medications for the treatment of AD was extracted for evaluation.

Results

Our review of the literature yielded 7 quantitative studies that evaluated adherence to topical medications in AD using electronic monitoring and/or self-reporting (Table).^7-13 Participant demographics, disease severity, drug and vehicle used, duration of treatment, and number of follow-up visits varied. All studies used medication event monitoring system caps on medication jars to objectively track patient adherence by recording the date and time when the cap was removed. To assess disease response, the studies used such measures as the Investigator Global Assessment scale, Eczema Area and Severity Index score, or other visual analog scales.

In all of the studies, treatment proved effective and disease severity declined from baseline regardless of the rate of adherence, with benefit continuing after treatment had ended.^7-13 Some results suggested that better adherence increased treatment efficacy and reduced disease severity.^8,9 However, one 10-day trial found no difference in severity and efficacy among participants who applied the medication at least once daily, missed applications some days, or applied the medication more than twice daily.¹³

Study participants typically overestimated their adherence to treatment compared to actual adherence rates, with most reporting near 100% adherence.^7-9,11,12 Average measured adherence rates ranged from 32% to 93% (Table). Adherence rates typically were highest at the beginning of the study and decreased as the study continued.^7-13 The study with the best average adherence rate of 93% had the shortest treatment period of 3 days,¹¹ and the study with the lowest average adherence rate of 32% had the longest treatment period of 8 weeks.⁷ The study with the lowest adherence rate was the only study wherein participants were blinded to their enrollment in the study, which would most closely mimic adherence rates in clinical practice.⁷ The participants in the other studies were not aware that their adherence was being monitored, but their behavior may have been influenced since they were aware of their enrollment in the study.

Many variables affect treatment adherence in patients with AD. Average adherence rates were significantly higher (P=.03) in participants with greater disease severity.⁷ There is conflicting evidence regarding the role of medication vehicle in treatment adherence. While Wilson et al⁹ did not find any difference in adherence based on medication vehicle, Yentzer et al¹² found vehicle characteristics and medication side effects were among patients’ top-ranked concerns about using topical medications. Sagransky et al¹⁰ compared treatment adherence between 2 groups of AD patients: one control group received a standard-of-care 4-week follow-up, and an active group received an additional 1-week follow-up. The mean adherence rate of the treatment group was 69% compared with 54% in the control group.¹⁰

Comment

Poor adherence to treatment is a pervasive problem in patients with AD. Our review of the literature confirmed that patients generally are not accurate historians of their medication usage, often reporting near-perfect treatment adherence even when actual adherence is poor. Rates of adherence from clinical trials are likely higher than those seen in clinical practice due in part to study incentives and differences between how patients in a study are treated compared to those in a physician’s clinic; for example, research study participants often have additional follow-up visits compared to those being treated in the clinical population and by virtue of being enrolled in a study are aware that their behavior is being monitored, which can increase treatment adherence.⁷

The dogma suggesting that tachyphylaxis can occur with long-term use of topical corticosteroids is not supported by clinical trials.¹⁴ Furthermore, in our review of the literature patient adherence was highest in the shortest study¹¹ and lowest in the longest study.⁷ Given that AD patients cannot benefit from a treatment if they do not use it, the supposed decrease in efficacy of topical corticosteroids over time may be because patients fail to use them consistently.

Our review of the literature was limited by the small body of research that exists on treatment adherence in AD patients, especially relating to topical medications, and did not reveal any studies evaluating systemic medications in AD. Of the studies we examined, sample sizes were small and treatment and follow-up periods were short. Our review only covered adherence to prescribed topical medications in AD, chiefly corticosteroids; thus, we did not evaluate adherence to other therapies (eg, emollients) in this patient population.

The existing research also is limited by the relative paucity of data showing a correlation between improved adherence to topical treatment and improved disease outcomes, which may be due to the methodological limitations of the study designs that have been used; for instance, studies may use objective monitors to describe daily adherence to treatment, but disease severity typically is measured over longer periods of time, usually every few weeks or months. Short-term data may not be an accurate demonstration of how participants’ actual treatment adherence impacts disease outcome, as the data does not account for more complex adherence factors; for example, participants who achieve good disease control using topical corticosteroids for an 8-week study period may actually demonstrate poor treatment adherence overall, as topical corticosteroids have good short-term efficacy and the patient may have stopped using the product after the first few weeks of the treatment period. In contrast, poorly adherent patients may never use the medication well enough to achieve improvement and may continue low-level use throughout the study period. Therefore, studies that measure disease severity at more regular intervals are required to show the true effect of treatment adherence on disease outcomes.

Since AD mainly affects children, family issues can pose special challenges to attaining good treatment adherence.^15,16 The physician–patient (or parent) relationship and the family’s perception of the patient’s disease severity are strong predictors of adherence to topical treatment.¹⁶ Potential barriers to adherence in the pediatric population are caregivers with negative beliefs about treatment, the time-consuming nature of applying topical therapies, or a child who is uncooperative.^15,17 In the treatment of infants, critical factors are caregiver availability and beliefs and fears about medications and their side effects, while in the teenage population, the desire to “fit in” and oppositional behavior can lead to poor adherence to treatment.¹⁷ Regardless of age, other barriers to treatment adherence are forgetfulness, belief that the drug is not working, and the messiness of treatment.¹⁷

Educational tools (eg, action plans, instructions about how to apply topical medications correctly) may be underutilized in patients with AD. If consistently implemented, these tools could have a positive impact on adherence to medication in patients with AD. For example, written action plans pioneered in the asthma community have shown to improve quality of life and reduce disease severity and may offer the same benefits for AD patients due to the similarities of the diseases.¹⁸ Since AD patients and their caregivers often are not well versed in how to apply topical medications correctly, efforts to educate patients could potentially increase adherence to treatment. In one study, AD patients began to use medications more effectively after applying a fluorescent cream to reveal affected areas they had missed, and clinicians were able to provide additional instruction based on the findings.¹⁹

Adherence to topical treatments among AD patients is a multifactorial issue. Regimens often are complex and inconvenient due to the need for multiple medications, the topical nature of the products, and the need for frequent application. To optimize prescription treatments, patients also must be diligent with preventive measures such as application of topical emollients and use of bathing techniques (eg, bleach baths). A way to overcome treatment complexity and increase adherence may be to provide a written action plan and involve the patient and caregiver in the plan’s development. If a drug formulation is not aesthetically acceptable to the patient (eg, the greasiness of an ointment), allowing the patient to choose the medication vehicle may increase satisfaction and use.¹² Fear of steroid side effects also is common among patients and caregivers and could be overcome with education about the product.²⁰

Conclusion

Treatment adherence can have a dramatic effect on diseases outcomes and can be particularly challenging in AD due to the use of topical medications with complex treatment regimens. Additionally, a large majority of patients with AD are children, from infants to teenagers, adding another layer of treatment challenges. Further research is needed to more definitively develop effective methods for enhancing treatment adherence in this patient population. Although enormous amounts of money are being spent to develop improved treatments for AD, we may be able to achieve far more benefit at a much lower cost by figuring out how to get patients to adhere to the treatments that are already available.

Inflammatory bowel disease (IBD) patients who experience skin lesions during anti–tumor necrosis factor therapy do not usually need to stop treatment, according to Isabelle Cleynen, Ph.D., of the University of Leuven (Belgium) and her associates.

In their retrospective study of 917 IBD patients who started treatment with infliximab at the University Hospitals Leuven between December 1994 and January 2009, 264 developed skin lesions during the follow-up period. The most common type was psoriasiform eczema, in 30.6% of the patients with lesions. Other common types included eczema (in 23.5%), xerosis cutis (10.6%), palmoplantar pustulosis (5.3%), and psoriasis (3.8%). Median cumulative doses and trough levels of infliximab were similar in people who developed skin lesions and those who did not.

Just over half of patients with skin lesions received only topical treatment, 1.9% received only systemic treatment, 28% received both, and 19.3% of patients required no specific treatment. Almost 11% of patients who developed skin lesions were forced to stop therapy. Reasons for stopping treatment included an intolerable location of lesions, concomitant itching or pain, recurring episodes, and concomitant arthralgia.

“Knowledge of the diagnostic and therapeutic criteria and the clinical course of these lesions should assist in their management. With referral to a dedicated dermatologist, most lesions can be treated and the need for interruption of anti-TNF therapy is rare,” the investigators concluded.

Find the full study in Annals of Internal Medicine (doi: 10.7326/M15-0729).

lfranki@frontlinemedcom.com

Inflammatory bowel disease (IBD) patients who experience skin lesions during anti–tumor necrosis factor therapy do not usually need to stop treatment, according to Isabelle Cleynen, Ph.D., of the University of Leuven (Belgium) and her associates.

In their retrospective study of 917 IBD patients who started treatment with infliximab at the University Hospitals Leuven between December 1994 and January 2009, 264 developed skin lesions during the follow-up period. The most common type was psoriasiform eczema, in 30.6% of the patients with lesions. Other common types included eczema (in 23.5%), xerosis cutis (10.6%), palmoplantar pustulosis (5.3%), and psoriasis (3.8%). Median cumulative doses and trough levels of infliximab were similar in people who developed skin lesions and those who did not.

Just over half of patients with skin lesions received only topical treatment, 1.9% received only systemic treatment, 28% received both, and 19.3% of patients required no specific treatment. Almost 11% of patients who developed skin lesions were forced to stop therapy. Reasons for stopping treatment included an intolerable location of lesions, concomitant itching or pain, recurring episodes, and concomitant arthralgia.

“Knowledge of the diagnostic and therapeutic criteria and the clinical course of these lesions should assist in their management. With referral to a dedicated dermatologist, most lesions can be treated and the need for interruption of anti-TNF therapy is rare,” the investigators concluded.

Find the full study in Annals of Internal Medicine (doi: 10.7326/M15-0729).

lfranki@frontlinemedcom.com

Inflammatory bowel disease (IBD) patients who experience skin lesions during anti–tumor necrosis factor therapy do not usually need to stop treatment, according to Isabelle Cleynen, Ph.D., of the University of Leuven (Belgium) and her associates.

In their retrospective study of 917 IBD patients who started treatment with infliximab at the University Hospitals Leuven between December 1994 and January 2009, 264 developed skin lesions during the follow-up period. The most common type was psoriasiform eczema, in 30.6% of the patients with lesions. Other common types included eczema (in 23.5%), xerosis cutis (10.6%), palmoplantar pustulosis (5.3%), and psoriasis (3.8%). Median cumulative doses and trough levels of infliximab were similar in people who developed skin lesions and those who did not.

Just over half of patients with skin lesions received only topical treatment, 1.9% received only systemic treatment, 28% received both, and 19.3% of patients required no specific treatment. Almost 11% of patients who developed skin lesions were forced to stop therapy. Reasons for stopping treatment included an intolerable location of lesions, concomitant itching or pain, recurring episodes, and concomitant arthralgia.

“Knowledge of the diagnostic and therapeutic criteria and the clinical course of these lesions should assist in their management. With referral to a dedicated dermatologist, most lesions can be treated and the need for interruption of anti-TNF therapy is rare,” the investigators concluded.

Find the full study in Annals of Internal Medicine (doi: 10.7326/M15-0729).

lfranki@frontlinemedcom.com

Children with a history of atopic disease (AD) are at a significantly higher risk for an anemia diagnosis than are children without AD, according to an analysis of two large U.S. population-based studies.

In addition, the risk of anemia increased with the number of caregiver-reported atopic disorders, reported the investigators, Dr. Jonathan I. Silverberg and his associates in the department of dermatology, Northwestern University, Chicago. A current diagnosis of eczema or asthma was associated with a significantly increased risk of anemia, particularly microcytic anemia, in the study, published online on Nov. 30 in JAMA Pediatrics (doi: 10.1001/jamapediatrics.2015.3065).

The authors evaluated data from the U.S. National Health Interview Survey (NHIS) on about 207,000 children and adolescents collected between 1997 and 2013, and from the National Health and Nutrition Examination Survey (NHANES) on nearly 31,000 children and adolescents between 1999 and 2012.

Data from the NHIS cohort found a significantly elevated anemia risk among children with a caregiver-reported history of hay fever, eczema, asthma, and food allergy (P less than .001 for all 4 disorders). After adjustments for age, sex, ethnicity and socioeconomic factors, the anemia risk for a child with any single atopic disorder was modestly elevated (adjusted odds ratio, 1.84; 95% confidence interval, 1.60-2.11; P less than .001). The adjusted risk among those with all four disorders was markedly elevated (adjusted OR, 7.87; 95% CI, 5.17-12.00; P less than .001).

In the NHANES cohort, the investigators found a current asthma or eczema diagnosis associated with anemia, as defined by laboratory assessment (adjusted OR, 1.33; 95% CI, 1.04-1.70; P = .02 for asthma; and an adjusted OR 1.93; 95% CI, 1.04-3.59; P = .04 for eczema).

©roobcio/thinkstockphotos.com

In the NHANES cohort, asthma was associated with an increased risk for microcytic anemia (adjusted OR, 1.61; 95% CI 1.09-2.38 P = .02). In the 2005-2006 NHANES cohort, a history of eczema was associated with an increased risk of microcytic anemia (adjusted OR, 2.03; 95% CI, 1.20-3.46; P = .009). But no significant associations for hay fever and any type of anemia were noted.

While the reasons for the observed association between atopic disease and anemia remain unknown and are probably multifactorial, physicians “should be aware that fatigue may be related to unrecognized anemia and not merely sleep loss owing to atopic dermatitis or airway disease,” the investigators wrote. Moreover, they noted, restricted diets to treat atopic disorders could play a role. “This finding underscores the importance of properly evaluating and ruling out suspected food allergy in children rather than placing them on empirical avoidance diets that might contribute to anemia,” they said.

The study was funded by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg and his coauthors, Kerry E. Drury and Matt Schaeffer, declared no conflicts of interest.

Children with a history of atopic disease (AD) are at a significantly higher risk for an anemia diagnosis than are children without AD, according to an analysis of two large U.S. population-based studies.

In addition, the risk of anemia increased with the number of caregiver-reported atopic disorders, reported the investigators, Dr. Jonathan I. Silverberg and his associates in the department of dermatology, Northwestern University, Chicago. A current diagnosis of eczema or asthma was associated with a significantly increased risk of anemia, particularly microcytic anemia, in the study, published online on Nov. 30 in JAMA Pediatrics (doi: 10.1001/jamapediatrics.2015.3065).

The authors evaluated data from the U.S. National Health Interview Survey (NHIS) on about 207,000 children and adolescents collected between 1997 and 2013, and from the National Health and Nutrition Examination Survey (NHANES) on nearly 31,000 children and adolescents between 1999 and 2012.

Data from the NHIS cohort found a significantly elevated anemia risk among children with a caregiver-reported history of hay fever, eczema, asthma, and food allergy (P less than .001 for all 4 disorders). After adjustments for age, sex, ethnicity and socioeconomic factors, the anemia risk for a child with any single atopic disorder was modestly elevated (adjusted odds ratio, 1.84; 95% confidence interval, 1.60-2.11; P less than .001). The adjusted risk among those with all four disorders was markedly elevated (adjusted OR, 7.87; 95% CI, 5.17-12.00; P less than .001).

In the NHANES cohort, the investigators found a current asthma or eczema diagnosis associated with anemia, as defined by laboratory assessment (adjusted OR, 1.33; 95% CI, 1.04-1.70; P = .02 for asthma; and an adjusted OR 1.93; 95% CI, 1.04-3.59; P = .04 for eczema).

©roobcio/thinkstockphotos.com

In the NHANES cohort, asthma was associated with an increased risk for microcytic anemia (adjusted OR, 1.61; 95% CI 1.09-2.38 P = .02). In the 2005-2006 NHANES cohort, a history of eczema was associated with an increased risk of microcytic anemia (adjusted OR, 2.03; 95% CI, 1.20-3.46; P = .009). But no significant associations for hay fever and any type of anemia were noted.

While the reasons for the observed association between atopic disease and anemia remain unknown and are probably multifactorial, physicians “should be aware that fatigue may be related to unrecognized anemia and not merely sleep loss owing to atopic dermatitis or airway disease,” the investigators wrote. Moreover, they noted, restricted diets to treat atopic disorders could play a role. “This finding underscores the importance of properly evaluating and ruling out suspected food allergy in children rather than placing them on empirical avoidance diets that might contribute to anemia,” they said.

The study was funded by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg and his coauthors, Kerry E. Drury and Matt Schaeffer, declared no conflicts of interest.

Children with a history of atopic disease (AD) are at a significantly higher risk for an anemia diagnosis than are children without AD, according to an analysis of two large U.S. population-based studies.

In addition, the risk of anemia increased with the number of caregiver-reported atopic disorders, reported the investigators, Dr. Jonathan I. Silverberg and his associates in the department of dermatology, Northwestern University, Chicago. A current diagnosis of eczema or asthma was associated with a significantly increased risk of anemia, particularly microcytic anemia, in the study, published online on Nov. 30 in JAMA Pediatrics (doi: 10.1001/jamapediatrics.2015.3065).

The authors evaluated data from the U.S. National Health Interview Survey (NHIS) on about 207,000 children and adolescents collected between 1997 and 2013, and from the National Health and Nutrition Examination Survey (NHANES) on nearly 31,000 children and adolescents between 1999 and 2012.

Data from the NHIS cohort found a significantly elevated anemia risk among children with a caregiver-reported history of hay fever, eczema, asthma, and food allergy (P less than .001 for all 4 disorders). After adjustments for age, sex, ethnicity and socioeconomic factors, the anemia risk for a child with any single atopic disorder was modestly elevated (adjusted odds ratio, 1.84; 95% confidence interval, 1.60-2.11; P less than .001). The adjusted risk among those with all four disorders was markedly elevated (adjusted OR, 7.87; 95% CI, 5.17-12.00; P less than .001).

In the NHANES cohort, the investigators found a current asthma or eczema diagnosis associated with anemia, as defined by laboratory assessment (adjusted OR, 1.33; 95% CI, 1.04-1.70; P = .02 for asthma; and an adjusted OR 1.93; 95% CI, 1.04-3.59; P = .04 for eczema).

©roobcio/thinkstockphotos.com

In the NHANES cohort, asthma was associated with an increased risk for microcytic anemia (adjusted OR, 1.61; 95% CI 1.09-2.38 P = .02). In the 2005-2006 NHANES cohort, a history of eczema was associated with an increased risk of microcytic anemia (adjusted OR, 2.03; 95% CI, 1.20-3.46; P = .009). But no significant associations for hay fever and any type of anemia were noted.

While the reasons for the observed association between atopic disease and anemia remain unknown and are probably multifactorial, physicians “should be aware that fatigue may be related to unrecognized anemia and not merely sleep loss owing to atopic dermatitis or airway disease,” the investigators wrote. Moreover, they noted, restricted diets to treat atopic disorders could play a role. “This finding underscores the importance of properly evaluating and ruling out suspected food allergy in children rather than placing them on empirical avoidance diets that might contribute to anemia,” they said.

The study was funded by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg and his coauthors, Kerry E. Drury and Matt Schaeffer, declared no conflicts of interest.

Food-antigen–specific immunoglobulin E (sIgE) levels were not clinically useful for predicting food allergy development in a study of infants with atopic dermatitis (AD).

The dual-phase study included 1,087 patients aged 3-18 months who had been diagnosed with AD for no more than 3 months prior to enrollment in the study and had at least mild disease activity. During the first phase of the study, which was a 36-month, randomized, double-blind, vehicle-controlled phase, half of patients were treated with placebo cream and the other half were treated with 1% pimecrolimus cream. In the second phase of the study, which was open-label, all patients received 1% pimecrolimus cream for up to 33 months or the patient’s 6th birthday, whichever occurred sooner. Patients were excluded if they received treatment with topical or systemic agents within 7 days before the first application of cream in the study.

The researchers followed food allergy development during both phases of the study. Other data collected by the researchers included sIgE levels for various foods at baseline and at the end of both phases of the study, with sIgE decision points having been assigned to each food.

By the end of the second phase of the trial, 15.9% of patients had developed a food allergy, with 292 days having been the median period of time that passed before the initial diagnosis of a food allergy was made. The most common food allergies were to peanuts, cow’s milk, and egg whites, occurring in 7%, 4%, and 4% of patients respectively. The percentage of patients with any allergy to food other than fish decreased over time. Higher levels of AD severity were predictive for the development of food allergy, with the percentage of patients who developed one or more food allergies by the end of the study having increased with increasing AD severity at baseline.

Total serum immunoglobulin E (IgE) and sIgE for milk, eggs, and peanuts measured at the end of the second phase also were increased in patients with increasing AD severity. Despite these findings, the positive predictive values for sIgE decision points for the foods tested were low (less than 0.6 for all values tested).

“SIgE decision points, both published values and the novel decision points used in this study, had high [negative predictive values], in particular for peanut[s], egg white[s], and cow’s milk. Thus, patients with mild AD with sIgE levels below these cutoffs would be unlikely to have or develop these specific allergies and would not benefit from food challenges or elimination diets. Similarly, elevated sIgE, as defined by the decision points tested, had very low [positive predictive values] for food allergy, both for sIgE values at baseline and at the end of the [first phase of the study] ... Thus, despite an increased likelihood of allergy development with increasing sIgE shown for cow’s milk, egg[s], and peanut[s], our data do not support the use of sIgE testing for the diagnosis of food allergy in subjects without a history of reaction to that food,” said Dr. Jonathan M. Spergelof the Children’s Hospital of Philadelphia and his colleagues.

Read the full study in Pediatrics (doi: 10.1542/peds.2015-1444).

klennon@frontlinemedcom.com

Food-antigen–specific immunoglobulin E (sIgE) levels were not clinically useful for predicting food allergy development in a study of infants with atopic dermatitis (AD).

The dual-phase study included 1,087 patients aged 3-18 months who had been diagnosed with AD for no more than 3 months prior to enrollment in the study and had at least mild disease activity. During the first phase of the study, which was a 36-month, randomized, double-blind, vehicle-controlled phase, half of patients were treated with placebo cream and the other half were treated with 1% pimecrolimus cream. In the second phase of the study, which was open-label, all patients received 1% pimecrolimus cream for up to 33 months or the patient’s 6th birthday, whichever occurred sooner. Patients were excluded if they received treatment with topical or systemic agents within 7 days before the first application of cream in the study.

The researchers followed food allergy development during both phases of the study. Other data collected by the researchers included sIgE levels for various foods at baseline and at the end of both phases of the study, with sIgE decision points having been assigned to each food.

By the end of the second phase of the trial, 15.9% of patients had developed a food allergy, with 292 days having been the median period of time that passed before the initial diagnosis of a food allergy was made. The most common food allergies were to peanuts, cow’s milk, and egg whites, occurring in 7%, 4%, and 4% of patients respectively. The percentage of patients with any allergy to food other than fish decreased over time. Higher levels of AD severity were predictive for the development of food allergy, with the percentage of patients who developed one or more food allergies by the end of the study having increased with increasing AD severity at baseline.

Total serum immunoglobulin E (IgE) and sIgE for milk, eggs, and peanuts measured at the end of the second phase also were increased in patients with increasing AD severity. Despite these findings, the positive predictive values for sIgE decision points for the foods tested were low (less than 0.6 for all values tested).

“SIgE decision points, both published values and the novel decision points used in this study, had high [negative predictive values], in particular for peanut[s], egg white[s], and cow’s milk. Thus, patients with mild AD with sIgE levels below these cutoffs would be unlikely to have or develop these specific allergies and would not benefit from food challenges or elimination diets. Similarly, elevated sIgE, as defined by the decision points tested, had very low [positive predictive values] for food allergy, both for sIgE values at baseline and at the end of the [first phase of the study] ... Thus, despite an increased likelihood of allergy development with increasing sIgE shown for cow’s milk, egg[s], and peanut[s], our data do not support the use of sIgE testing for the diagnosis of food allergy in subjects without a history of reaction to that food,” said Dr. Jonathan M. Spergelof the Children’s Hospital of Philadelphia and his colleagues.

Read the full study in Pediatrics (doi: 10.1542/peds.2015-1444).

klennon@frontlinemedcom.com

Food-antigen–specific immunoglobulin E (sIgE) levels were not clinically useful for predicting food allergy development in a study of infants with atopic dermatitis (AD).

The dual-phase study included 1,087 patients aged 3-18 months who had been diagnosed with AD for no more than 3 months prior to enrollment in the study and had at least mild disease activity. During the first phase of the study, which was a 36-month, randomized, double-blind, vehicle-controlled phase, half of patients were treated with placebo cream and the other half were treated with 1% pimecrolimus cream. In the second phase of the study, which was open-label, all patients received 1% pimecrolimus cream for up to 33 months or the patient’s 6th birthday, whichever occurred sooner. Patients were excluded if they received treatment with topical or systemic agents within 7 days before the first application of cream in the study.

The researchers followed food allergy development during both phases of the study. Other data collected by the researchers included sIgE levels for various foods at baseline and at the end of both phases of the study, with sIgE decision points having been assigned to each food.

By the end of the second phase of the trial, 15.9% of patients had developed a food allergy, with 292 days having been the median period of time that passed before the initial diagnosis of a food allergy was made. The most common food allergies were to peanuts, cow’s milk, and egg whites, occurring in 7%, 4%, and 4% of patients respectively. The percentage of patients with any allergy to food other than fish decreased over time. Higher levels of AD severity were predictive for the development of food allergy, with the percentage of patients who developed one or more food allergies by the end of the study having increased with increasing AD severity at baseline.

Total serum immunoglobulin E (IgE) and sIgE for milk, eggs, and peanuts measured at the end of the second phase also were increased in patients with increasing AD severity. Despite these findings, the positive predictive values for sIgE decision points for the foods tested were low (less than 0.6 for all values tested).

“SIgE decision points, both published values and the novel decision points used in this study, had high [negative predictive values], in particular for peanut[s], egg white[s], and cow’s milk. Thus, patients with mild AD with sIgE levels below these cutoffs would be unlikely to have or develop these specific allergies and would not benefit from food challenges or elimination diets. Similarly, elevated sIgE, as defined by the decision points tested, had very low [positive predictive values] for food allergy, both for sIgE values at baseline and at the end of the [first phase of the study] ... Thus, despite an increased likelihood of allergy development with increasing sIgE shown for cow’s milk, egg[s], and peanut[s], our data do not support the use of sIgE testing for the diagnosis of food allergy in subjects without a history of reaction to that food,” said Dr. Jonathan M. Spergelof the Children’s Hospital of Philadelphia and his colleagues.

Read the full study in Pediatrics (doi: 10.1542/peds.2015-1444).

klennon@frontlinemedcom.com

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

A smaller percentage of atopic dermatitis (AD) patients with high baseline serum total IgE achieved a good response to treatment, compared with AD patients with lower serum total IgE at baseline, in a retrospective study of Finnish patients.

After adjustment of the data from the multivariate analyses, “the presence of contact allergies and high baseline IgE values [greater than or equal to] 10,0000 IU/mL remained risk factors for poor long-term outcome and were statistically significantly negatively associated with a good treatment response (OR [odds ratio], 0.162 and 0.062, respectively), and with complete remission (OR 0.287 and 0.158, respectively),” wrote Ville Kiiski of Skin and Allergy Hospital, Helsinki, and his colleagues.

©aniaostudio/Thinkstock.com

The study comprised 169 individuals aged 14-78 with atopic dermatitis. Patients were reevaluated a mean of 4.15 years following the first visit to the specialized AD clinic at Skin and Allergy Hospital of Helsinki University Central Hospital. They received topical treatments as either maintenance therapy with tacrolimus or maintenance treatment with either a combination of topical tacrolimus and topical corticosteroids, or topical corticosteroids alone. A dermatologist provided the patients with a long-term treatment plan, and a nurse provided “hands-on training for adequate topical therapy regimens,” when necessary.

“In patients with baseline IgE [greater than or equal to] 10,000 IU/mL, proportions achieving complete remission or a good treatment response were only 8.7% and 14.3%, compared with 51.6% and 79.7% in patients with IgE [less than] 1,000 IU/mL, and 36.9% and 58.1% in patients with IgE 1,000-10.000 IU/mL, respectively,” the researchers wrote.

While this study’s results suggest that serum total IgE is a predictor of long-term treatment outcome in AD patients, a larger, prospective study is needed to confirm this, they added.

The authors declared no conflicts of interest.

Read the study in Acta Dermato-Venereologica (doi: 10.2340/00015555-2126).

klennon@frontlinemedcom.com

A smaller percentage of atopic dermatitis (AD) patients with high baseline serum total IgE achieved a good response to treatment, compared with AD patients with lower serum total IgE at baseline, in a retrospective study of Finnish patients.

After adjustment of the data from the multivariate analyses, “the presence of contact allergies and high baseline IgE values [greater than or equal to] 10,0000 IU/mL remained risk factors for poor long-term outcome and were statistically significantly negatively associated with a good treatment response (OR [odds ratio], 0.162 and 0.062, respectively), and with complete remission (OR 0.287 and 0.158, respectively),” wrote Ville Kiiski of Skin and Allergy Hospital, Helsinki, and his colleagues.

©aniaostudio/Thinkstock.com

The study comprised 169 individuals aged 14-78 with atopic dermatitis. Patients were reevaluated a mean of 4.15 years following the first visit to the specialized AD clinic at Skin and Allergy Hospital of Helsinki University Central Hospital. They received topical treatments as either maintenance therapy with tacrolimus or maintenance treatment with either a combination of topical tacrolimus and topical corticosteroids, or topical corticosteroids alone. A dermatologist provided the patients with a long-term treatment plan, and a nurse provided “hands-on training for adequate topical therapy regimens,” when necessary.

“In patients with baseline IgE [greater than or equal to] 10,000 IU/mL, proportions achieving complete remission or a good treatment response were only 8.7% and 14.3%, compared with 51.6% and 79.7% in patients with IgE [less than] 1,000 IU/mL, and 36.9% and 58.1% in patients with IgE 1,000-10.000 IU/mL, respectively,” the researchers wrote.

While this study’s results suggest that serum total IgE is a predictor of long-term treatment outcome in AD patients, a larger, prospective study is needed to confirm this, they added.

The authors declared no conflicts of interest.

Read the study in Acta Dermato-Venereologica (doi: 10.2340/00015555-2126).

klennon@frontlinemedcom.com

A smaller percentage of atopic dermatitis (AD) patients with high baseline serum total IgE achieved a good response to treatment, compared with AD patients with lower serum total IgE at baseline, in a retrospective study of Finnish patients.

After adjustment of the data from the multivariate analyses, “the presence of contact allergies and high baseline IgE values [greater than or equal to] 10,0000 IU/mL remained risk factors for poor long-term outcome and were statistically significantly negatively associated with a good treatment response (OR [odds ratio], 0.162 and 0.062, respectively), and with complete remission (OR 0.287 and 0.158, respectively),” wrote Ville Kiiski of Skin and Allergy Hospital, Helsinki, and his colleagues.

©aniaostudio/Thinkstock.com

The study comprised 169 individuals aged 14-78 with atopic dermatitis. Patients were reevaluated a mean of 4.15 years following the first visit to the specialized AD clinic at Skin and Allergy Hospital of Helsinki University Central Hospital. They received topical treatments as either maintenance therapy with tacrolimus or maintenance treatment with either a combination of topical tacrolimus and topical corticosteroids, or topical corticosteroids alone. A dermatologist provided the patients with a long-term treatment plan, and a nurse provided “hands-on training for adequate topical therapy regimens,” when necessary.

“In patients with baseline IgE [greater than or equal to] 10,000 IU/mL, proportions achieving complete remission or a good treatment response were only 8.7% and 14.3%, compared with 51.6% and 79.7% in patients with IgE [less than] 1,000 IU/mL, and 36.9% and 58.1% in patients with IgE 1,000-10.000 IU/mL, respectively,” the researchers wrote.

While this study’s results suggest that serum total IgE is a predictor of long-term treatment outcome in AD patients, a larger, prospective study is needed to confirm this, they added.

The authors declared no conflicts of interest.

Read the study in Acta Dermato-Venereologica (doi: 10.2340/00015555-2126).

klennon@frontlinemedcom.com

Pediatric eczema was significantly associated with a higher risk of speech disorder, reported Dr. Mark A. Strom and his coauthors from Northwestern University, Chicago.

A retrospective analysis of 354,416 children in 19 U.S. population–based cohorts found that the prevalence of speech disorder was 4.7% among the children with eczema (95% confidence interval, 4.5%-5.0%), compared with 2.2% among those without eczema (95% CI; 2.2%-2.3%).

Results from a multivariate analysis showed that eczema was associated with increased odds of speech disorder (adjusted odds ratio = 1.81 [1.57-2.05]; P less than .001). Mild (1.36 [1.02-1.81]; P = .03) and severe (3.56 [1.70-7.48]; P less than .001) eczema were associated with higher risk of speech disorder, the investigators said.

The findings were based on results from the 2003-2004 and 2007-2008 National Survey of Children’s Health, and the 1997-2013 National Health Interview Survey.

Read the study in the Journal of Pediatrics.

Pediatric eczema was significantly associated with a higher risk of speech disorder, reported Dr. Mark A. Strom and his coauthors from Northwestern University, Chicago.

A retrospective analysis of 354,416 children in 19 U.S. population–based cohorts found that the prevalence of speech disorder was 4.7% among the children with eczema (95% confidence interval, 4.5%-5.0%), compared with 2.2% among those without eczema (95% CI; 2.2%-2.3%).

Results from a multivariate analysis showed that eczema was associated with increased odds of speech disorder (adjusted odds ratio = 1.81 [1.57-2.05]; P less than .001). Mild (1.36 [1.02-1.81]; P = .03) and severe (3.56 [1.70-7.48]; P less than .001) eczema were associated with higher risk of speech disorder, the investigators said.

The findings were based on results from the 2003-2004 and 2007-2008 National Survey of Children’s Health, and the 1997-2013 National Health Interview Survey.

Read the study in the Journal of Pediatrics.

Pediatric eczema was significantly associated with a higher risk of speech disorder, reported Dr. Mark A. Strom and his coauthors from Northwestern University, Chicago.

A retrospective analysis of 354,416 children in 19 U.S. population–based cohorts found that the prevalence of speech disorder was 4.7% among the children with eczema (95% confidence interval, 4.5%-5.0%), compared with 2.2% among those without eczema (95% CI; 2.2%-2.3%).

Results from a multivariate analysis showed that eczema was associated with increased odds of speech disorder (adjusted odds ratio = 1.81 [1.57-2.05]; P less than .001). Mild (1.36 [1.02-1.81]; P = .03) and severe (3.56 [1.70-7.48]; P less than .001) eczema were associated with higher risk of speech disorder, the investigators said.

The findings were based on results from the 2003-2004 and 2007-2008 National Survey of Children’s Health, and the 1997-2013 National Health Interview Survey.

Read the study in the Journal of Pediatrics.