Atopic Dermatitis

Key clinical point: A cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) demonstrated superior efficacy than a vehicle cream and was well-tolerated in children aged 2-18 years with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 4, patients receiving EHA cream achieved a significantly higher clinical improvement in SCORing AD (mean difference [MD] −6.62; P < .001) and Investigator’s Global Assessment scores (MD −0.69; P < .001) than those receiving vehicle cream. Mild adverse events like skin erythema, pruritus, and burning skin were reported by 23.5% of patients receiving EHA cream and 5.7% of patients receiving vehicle cream.

Study details: Findings are from an observer-blind, multicenter clinical trial including 57 children aged 2-18 years with mild-to-moderate AD who were randomly assigned to receive EHA or vehicle cream twice daily for 4 weeks.

Disclosures: This study was funded by BODERM SA. The authors declared no conflicts of interest.

Source: Alexopoulos A et al. A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis. Pediatr Dermatol. 2022 (Aug 29). Doi: 10.1111/pde.15117

Key clinical point: A cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) demonstrated superior efficacy than a vehicle cream and was well-tolerated in children aged 2-18 years with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 4, patients receiving EHA cream achieved a significantly higher clinical improvement in SCORing AD (mean difference [MD] −6.62; P < .001) and Investigator’s Global Assessment scores (MD −0.69; P < .001) than those receiving vehicle cream. Mild adverse events like skin erythema, pruritus, and burning skin were reported by 23.5% of patients receiving EHA cream and 5.7% of patients receiving vehicle cream.

Study details: Findings are from an observer-blind, multicenter clinical trial including 57 children aged 2-18 years with mild-to-moderate AD who were randomly assigned to receive EHA or vehicle cream twice daily for 4 weeks.

Disclosures: This study was funded by BODERM SA. The authors declared no conflicts of interest.

Source: Alexopoulos A et al. A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis. Pediatr Dermatol. 2022 (Aug 29). Doi: 10.1111/pde.15117

Key clinical point: A cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) demonstrated superior efficacy than a vehicle cream and was well-tolerated in children aged 2-18 years with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 4, patients receiving EHA cream achieved a significantly higher clinical improvement in SCORing AD (mean difference [MD] −6.62; P < .001) and Investigator’s Global Assessment scores (MD −0.69; P < .001) than those receiving vehicle cream. Mild adverse events like skin erythema, pruritus, and burning skin were reported by 23.5% of patients receiving EHA cream and 5.7% of patients receiving vehicle cream.

Study details: Findings are from an observer-blind, multicenter clinical trial including 57 children aged 2-18 years with mild-to-moderate AD who were randomly assigned to receive EHA or vehicle cream twice daily for 4 weeks.

Disclosures: This study was funded by BODERM SA. The authors declared no conflicts of interest.

Source: Alexopoulos A et al. A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis. Pediatr Dermatol. 2022 (Aug 29). Doi: 10.1111/pde.15117

Key clinical point: Ruxolitinib cream demonstrated rapid and sustained improvement in itch in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: A significantly higher proportion of patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream achieved ≥2-point reduction in itch numerical rating scale (NRS2) score as rapidly as within 12 hours (16.3% and 13.1% vs 6.9%; P < .05), with further improvements at week 8 (58.3% and 65.1% vs 29.4%; P < .0001). In patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream, time to achieve itch NRS2 score was shorter (5 and 4 vs 17 days).

Study details: Findings are from a pooled analysis of two phase 3 trials, TRuE-AD1 and TRuE-AD2, including 1249 patients with mild-to-moderate AD who were randomly assigned to receive ruxolitinib (0.75% or 1.5%) or vehicle cream twice daily for 8 weeks.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants or receiving research grants and honoraria from several sources.

Source: Blauvelt A et al. Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2022 (Sep 6). Doi: 10.1111/jdv.18571

Key clinical point: Ruxolitinib cream demonstrated rapid and sustained improvement in itch in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: A significantly higher proportion of patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream achieved ≥2-point reduction in itch numerical rating scale (NRS2) score as rapidly as within 12 hours (16.3% and 13.1% vs 6.9%; P < .05), with further improvements at week 8 (58.3% and 65.1% vs 29.4%; P < .0001). In patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream, time to achieve itch NRS2 score was shorter (5 and 4 vs 17 days).

Study details: Findings are from a pooled analysis of two phase 3 trials, TRuE-AD1 and TRuE-AD2, including 1249 patients with mild-to-moderate AD who were randomly assigned to receive ruxolitinib (0.75% or 1.5%) or vehicle cream twice daily for 8 weeks.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants or receiving research grants and honoraria from several sources.

Source: Blauvelt A et al. Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2022 (Sep 6). Doi: 10.1111/jdv.18571

Key clinical point: Ruxolitinib cream demonstrated rapid and sustained improvement in itch in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: A significantly higher proportion of patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream achieved ≥2-point reduction in itch numerical rating scale (NRS2) score as rapidly as within 12 hours (16.3% and 13.1% vs 6.9%; P < .05), with further improvements at week 8 (58.3% and 65.1% vs 29.4%; P < .0001). In patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream, time to achieve itch NRS2 score was shorter (5 and 4 vs 17 days).

Study details: Findings are from a pooled analysis of two phase 3 trials, TRuE-AD1 and TRuE-AD2, including 1249 patients with mild-to-moderate AD who were randomly assigned to receive ruxolitinib (0.75% or 1.5%) or vehicle cream twice daily for 8 weeks.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants or receiving research grants and honoraria from several sources.

Source: Blauvelt A et al. Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2022 (Sep 6). Doi: 10.1111/jdv.18571

Key clinical point: Topical brepocitinib cream showed significant efficacy in reducing disease severity and was well-tolerated in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: The reduction in the mean Eczema Area and Severity Index at week 6 was significantly higher with 1% brepocitinib cream once daily (QD) vs vehicle QD (−70.1% vs −44.4%) and 1% brepocitinib  cream twice daily (BID) vs vehicle BID (−75.0% vs −47.6%; both P < .05). No serious adverse events or deaths were reported.

Study details: Findings are from a double-blind, dose-ranging, phase 2 study including 292 patients with mild-to-moderate AD who were randomly assigned to receive brepocitinib (0.1% QD, 0.3% QD or BID, 1.0% QD or BID, or 3.0% QD) or vehicle (QD or BID).

Disclosures: This study was sponsored by Pfizer Inc. Nine authors declared being shareholders and current or former employees of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Landis MN et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: A phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group study. Br J Dermatol. 2022 (Aug 20). Doi: 10.1111/bjd.21826

Key clinical point: Topical brepocitinib cream showed significant efficacy in reducing disease severity and was well-tolerated in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: The reduction in the mean Eczema Area and Severity Index at week 6 was significantly higher with 1% brepocitinib cream once daily (QD) vs vehicle QD (−70.1% vs −44.4%) and 1% brepocitinib  cream twice daily (BID) vs vehicle BID (−75.0% vs −47.6%; both P < .05). No serious adverse events or deaths were reported.

Study details: Findings are from a double-blind, dose-ranging, phase 2 study including 292 patients with mild-to-moderate AD who were randomly assigned to receive brepocitinib (0.1% QD, 0.3% QD or BID, 1.0% QD or BID, or 3.0% QD) or vehicle (QD or BID).

Disclosures: This study was sponsored by Pfizer Inc. Nine authors declared being shareholders and current or former employees of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Landis MN et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: A phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group study. Br J Dermatol. 2022 (Aug 20). Doi: 10.1111/bjd.21826

Key clinical point: Topical brepocitinib cream showed significant efficacy in reducing disease severity and was well-tolerated in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: The reduction in the mean Eczema Area and Severity Index at week 6 was significantly higher with 1% brepocitinib cream once daily (QD) vs vehicle QD (−70.1% vs −44.4%) and 1% brepocitinib  cream twice daily (BID) vs vehicle BID (−75.0% vs −47.6%; both P < .05). No serious adverse events or deaths were reported.

Study details: Findings are from a double-blind, dose-ranging, phase 2 study including 292 patients with mild-to-moderate AD who were randomly assigned to receive brepocitinib (0.1% QD, 0.3% QD or BID, 1.0% QD or BID, or 3.0% QD) or vehicle (QD or BID).

Disclosures: This study was sponsored by Pfizer Inc. Nine authors declared being shareholders and current or former employees of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Landis MN et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: A phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group study. Br J Dermatol. 2022 (Aug 20). Doi: 10.1111/bjd.21826

Key clinical point: The results of this meta-analysis do not demonstrate an elevated risk for incident venous thromboembolism (VTE) in patients with atopic dermatitis (AD), particularly among those receiving treatment with Janus kinase (JAK) inhibitors.

Major finding: The risk for incident VTE was similar among participants with vs without AD (pooled hazard ratio 0.95; 95% CI 0.62-1.45). Among patients with AD who received JAK inhibitors vs placebo /dupilumab, 0.05% vs 0.03% reported VTE (Mantel-Haenszel risk difference 0; 95% CI 0-0).

Study details: Findings are from a meta-analysis of two cohort studies including 458,206 participants with (n = 229,103) and without AD (n = 229,103) and 15 randomized controlled trials including 8787 patients with AD who received an interventional treatment with JAK inhibitors or a control treatment with dupilumab or placebo.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Chen TL et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: A systematic review and meta-analysis. JAMA Dermatol. 2022;e223516 (Aug 24). Doi: 10.1001/jamadermatol.2022.3516

Key clinical point: The results of this meta-analysis do not demonstrate an elevated risk for incident venous thromboembolism (VTE) in patients with atopic dermatitis (AD), particularly among those receiving treatment with Janus kinase (JAK) inhibitors.

Major finding: The risk for incident VTE was similar among participants with vs without AD (pooled hazard ratio 0.95; 95% CI 0.62-1.45). Among patients with AD who received JAK inhibitors vs placebo /dupilumab, 0.05% vs 0.03% reported VTE (Mantel-Haenszel risk difference 0; 95% CI 0-0).

Study details: Findings are from a meta-analysis of two cohort studies including 458,206 participants with (n = 229,103) and without AD (n = 229,103) and 15 randomized controlled trials including 8787 patients with AD who received an interventional treatment with JAK inhibitors or a control treatment with dupilumab or placebo.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Chen TL et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: A systematic review and meta-analysis. JAMA Dermatol. 2022;e223516 (Aug 24). Doi: 10.1001/jamadermatol.2022.3516

Key clinical point: The results of this meta-analysis do not demonstrate an elevated risk for incident venous thromboembolism (VTE) in patients with atopic dermatitis (AD), particularly among those receiving treatment with Janus kinase (JAK) inhibitors.

Major finding: The risk for incident VTE was similar among participants with vs without AD (pooled hazard ratio 0.95; 95% CI 0.62-1.45). Among patients with AD who received JAK inhibitors vs placebo /dupilumab, 0.05% vs 0.03% reported VTE (Mantel-Haenszel risk difference 0; 95% CI 0-0).

Study details: Findings are from a meta-analysis of two cohort studies including 458,206 participants with (n = 229,103) and without AD (n = 229,103) and 15 randomized controlled trials including 8787 patients with AD who received an interventional treatment with JAK inhibitors or a control treatment with dupilumab or placebo.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Chen TL et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: A systematic review and meta-analysis. JAMA Dermatol. 2022;e223516 (Aug 24). Doi: 10.1001/jamadermatol.2022.3516

Key clinical point: Dupilumab demonstrated good overall drug survival for up to 3 years in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab showed good overall drug survival rates at 1-year (90.3%), 2-year (85.9%), and 3-year (78.6%). The use of immunosuppressant drugs at baseline was associated with shorter drug survival owing to ineffectiveness (hazard ratio [HR] 2.64; 95% CI 1.10-6.37) and adverse events (HR 2.69; 95% CI 1.32-5.48).

Study details: Findings are from an analysis of the BioDay registry data of 715 adult patients with moderate-to-severe AD who received dupilumab and were followed-up for ≥4 weeks.

Disclosures: The BioDay registry was sponsored by Sanofi Genzyme. The authors declared receiving grants, personal fees, speaking fees, financial support or nonfinancial support from several sources.

Source: Spekhorst LS et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: Long-term results from the daily practice BioDay registry. JAMA Dermatol. 2022;e223014 (Aug 10). Doi: 10.1001/jamadermatol.2022.3014

Key clinical point: Dupilumab demonstrated good overall drug survival for up to 3 years in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab showed good overall drug survival rates at 1-year (90.3%), 2-year (85.9%), and 3-year (78.6%). The use of immunosuppressant drugs at baseline was associated with shorter drug survival owing to ineffectiveness (hazard ratio [HR] 2.64; 95% CI 1.10-6.37) and adverse events (HR 2.69; 95% CI 1.32-5.48).

Study details: Findings are from an analysis of the BioDay registry data of 715 adult patients with moderate-to-severe AD who received dupilumab and were followed-up for ≥4 weeks.

Disclosures: The BioDay registry was sponsored by Sanofi Genzyme. The authors declared receiving grants, personal fees, speaking fees, financial support or nonfinancial support from several sources.

Source: Spekhorst LS et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: Long-term results from the daily practice BioDay registry. JAMA Dermatol. 2022;e223014 (Aug 10). Doi: 10.1001/jamadermatol.2022.3014

Key clinical point: Dupilumab demonstrated good overall drug survival for up to 3 years in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab showed good overall drug survival rates at 1-year (90.3%), 2-year (85.9%), and 3-year (78.6%). The use of immunosuppressant drugs at baseline was associated with shorter drug survival owing to ineffectiveness (hazard ratio [HR] 2.64; 95% CI 1.10-6.37) and adverse events (HR 2.69; 95% CI 1.32-5.48).

Study details: Findings are from an analysis of the BioDay registry data of 715 adult patients with moderate-to-severe AD who received dupilumab and were followed-up for ≥4 weeks.

Disclosures: The BioDay registry was sponsored by Sanofi Genzyme. The authors declared receiving grants, personal fees, speaking fees, financial support or nonfinancial support from several sources.

Source: Spekhorst LS et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: Long-term results from the daily practice BioDay registry. JAMA Dermatol. 2022;e223014 (Aug 10). Doi: 10.1001/jamadermatol.2022.3014

Even with recent pharmacologic treatment advances, narrowband UVB (NB-UVB) phototherapy remains a versatile, safe, and efficacious adjunctive or exclusive treatment for multiple dermatologic conditions, including psoriasis and atopic dermatitis. ^1-9 Some providers choose NB-UVB phototherapy as a first-line treatment for older adult patients who frequently use multiple treatment modalities for more than 1 health condition. Older adults with atopic dermatitis and psoriasis are at higher risk for comorbidities such as autoimmune disorders, diabetes mellitus, dyslipidemia, sleep disorders, neuropsychiatric disorders, and cardiovascular disease that can complicate treatment compared with their peers without these dermatologic diagnoses. ^10-12 Polypharmacy (ie, the use of 5 or more daily medications), frequently associated with these conditions, contributes to prescribers pursuing NB-UVB phototherapy as a nonpharmacologic treatment, but some providers wonder if it is as effective and safe for their older patients compared with younger patients.

In a prior study, Matthews et al¹³ reported that 96% (50/52) of patients older than 65 years achieved medium to high levels of clearance with NB-UVB phototherapy. Nonetheless, 2 other findings in this study related to the number of treatments required to achieve clearance (ie, clearance rates) and erythema rates prompted further investigation. The first finding was higher-than-expected clearance rates. Older adults had a clearance rate with a mean of 33 treatments compared to prior studies featuring mean clearance rates of 20 to 28 treatments.^7,8,14-16 This finding resembled a study in the United Kingdom¹⁷ with a median clearance rate in older adults of 30 treatments. In contrast, the median clearance rate from a study in Turkey¹⁸ was 42 treatments in older adults. We hypothesized that more photosensitizing medications used in older vs younger adults prompted more dose adjustments with NB-UVB phototherapy to avoid burning (ie, erythema) at baseline and throughout the treatment course. These dose adjustments may have increased the overall clearance rates. If true, we predicted that younger adults treated with the same protocol would have cleared more quickly, either because of age-related differences or because they likely had fewer comorbidities and therefore fewer medications.

The second finding from Matthews et al¹³ that warranted further investigation was a higher erythema rate compared to the older adult study from the United Kingdom.¹⁷ We hypothesized that potentially greater use of photosensitizing medications in the United States could explain the higher erythema rates. Although medication-induced photosensitivity is less likely with NB-UVB phototherapy than with UVA, certain medications can cause UVB photosensitivity, including thiazides, quinidine, calcium channel antagonists, phenothiazines, and nonsteroidal anti-inflammatory drugs.^8,19,20 Therefore, photosensitizing medication use either at baseline or during a course of NB-UVB phototherapy could increase the risk for erythema. Age-related skin changes also have been considered as a potential cause for erythema. One study found that the skin of older patients was more sensitive than younger patients, resulting in a lower minimal erythema dose (MED)¹⁴—the lowest UV dose that results in erythema.²¹ Others, however, found similar MEDs across age groups, but older adults experienced more intense erythema in the late phase of NB-UVB treatment.^22,23 Such conflicting findings indicate that questions remain regarding the risk for erythema in older patients and if photosensitizing medications are responsible for an increased risk.

This retrospective study aimed to determine if NB-UVB phototherapy is equally effective in both older and younger adults treated with the same protocol; to examine the association between the use of photosensitizing medications and clearance rates in both older and younger adults; and to examine the association between the use of photosensitizing medications and erythema rates in older vs younger adults.

Methods

Study Design and Patients—This retrospective cohort study used billing records to identify patients who received NB-UVB phototherapy at 3 different clinical sites within a large US health care system in Washington (Group Health Cooperative, now Kaiser Permanente Washington), serving more than 600,000 patients between January 1, 2012, and December 31, 2016. The institutional review board of Kaiser Permanente Washington Health Research Institute approved this study (IRB 1498087-4). Younger adults were classified as those 64 years or younger and older adults as those 65 years and older at the start of their phototherapy regimen. A power analysis determined that the optimal sample size for this study was 250 patients.

Individuals were excluded if they had fewer than 6 phototherapy treatments; a diagnosis of vitiligo, photosensitivity dermatitis, morphea, or pityriasis rubra pilaris; and/or treatment of the hands or feet only.

Phototherapy Protocol—Using a 48-lamp NB-UVB unit, trained phototherapy nurses provided all treatments following standardized treatment protocols¹³ based on previously published phototherapy guidelines.²⁴ Nurses determined each patient’s disease clearance level using a 3-point clearance scale (high, medium, low).¹³ Each patient’s starting dose was determined based on the estimated MED for their skin phototype. If the patient was using photosensitizing medications, the protocol indicated a need for a decreased starting dose—down 25% to 50%—depending on the presumed level of photosensitivity. All clinical sites used the same protocol, but decisions about adjustments within this range were made by individual registered nurses and dermatologists, which could lead to variability across sites. Protocols also directed nurses to query patients about specific treatment responses, including erythema, tenderness, or itching; how their condition was responding; use of photosensitizing medications; missed treatments; and placement of shielding. Doses were adjusted accordingly.

Statistical Analysis—Data were analyzed using Stata statistical software (StataCorp LLC). Univariate analyses were used to examine the data and identify outliers, bad values, and missing data, as well as to calculate descriptive statistics. Pearson χ² and Fisher exact statistics were used to calculate differences in categorical variables. Linear multivariate regression models and logistic multivariate models were used to examine statistical relationships between variables. Statistical significance was defined as P≤.05.

Results

Patient Characteristics—Medical records were reviewed for 172 patients who received phototherapy between 2012 and 2016. Patients ranged in age from 23 to 91 years, with 102 patients 64 years and younger and 70 patients 65 years and older. Tables 1 and 2 outline the patient characteristics and conditions treated.

Phototherapy Effectiveness—Narrowband UVB phototherapy was found to be equally effective in older vs younger adults, with 82.9% of older adults (n=58) achieving a high level of clearance vs 80.4% (n=82) of younger adults, and 5.7% (n=4) of older adults achieved a medium level of clearance vs 10% (n=10) of younger adults (Table 3). Although older adults had slightly faster clearance rates on average (34.6 vs 37.2 treatments), these differences were not significant.

Photosensitizing Medications, Clearance Levels, and Clearance Rates—There was no significant association between clearance levels and number of photosensitizing medications in either younger (Figure 1) or older (Figure 2) adults. There was a wide range of clearance rates in both groups (Table 3), but no relationship was identified between clearance rates and photosensitizing medications or age (Figure 3). Clinic C had higher overall clearance rates for both age groups compared to the other clinics (Figure 4), but the clearance levels were still equivalent. No consistent pattern emerged indicating that age was a factor for the slower clearance at this site, and no relationship was identified between taking photosensitizing medications and clearance levels (Fisher exact test, P=.467) or clearance rates (t[149]=0.75; P=.45).

Frequency of Treatments and Clearance Rates—Older adults more consistently completed the recommended frequency of treatments—3 times weekly—compared to younger adults (74.3% vs 58.5%). However, all patients who completed 3 treatments per week required a similar number of treatments to clear (older adults, mean [SD]: 35.7 [21.6]; younger adults, mean [SD]: 34.7 [19.0]; P=.85). Among patients completing 2 or fewer treatments per week, older adults required a mean (SD) of only 31 (9.0) treatments to clear vs 41.5 (21.3) treatments to clear for younger adults, but the difference was not statistically significant (P=.08). However, even those with suboptimal frequency ultimately achieved similar clearance levels.

Photosensitizing Medications and Erythema Rates—Many patients in both age groups took medications that listed photosensitivity as a potential side effect (77.1% of older adults and 60.8% of younger adults). Of them, most patients took only 1 or 2 photosensitizing medications. However, significantly more older patients took 3 or more photosensitizing medications (28.6% vs 12.7%; P=.01)(Table 3). Asymptomatic (grade 1) erythema was unrelated to medication use and quite common in all adults (48.6% of older adults and 60.8% of younger adults). Most patients had only a few episodes of grade 1 erythema (mean [SD], 1.2 [2.9] in older adults and 1.6 [2.2] in younger adults). More older adults had grade 2 erythema (28.6%) compared to younger adults (17.6%). Patients using 3 or more photosensitizing medications were twice as likely to experience grade 2 erythema. Grades 3 and 4 erythema were extremely rare; none of the patients stopped phototherapy because they experienced erythema.

Overall, phototherapy nurses adjusted the starting dose according to the phototype-based protocol an average of 69% of the time for patients on medications with photosensitivity listed as a potential side effect. However, the frequency depended significantly on the clinic (clinic A, 24%; clinic B, 92%; clinic C, 87%)(P≤.001). Nurses across all clinics consistently decreased the treatment dose when patients reported starting new photosensitizing medications. Patients with adjusted starting doses had slightly but not significantly higher clearance rates compared to those without (mean, 37.8 vs 35.5; t(104)=0.58; P=.56).

Comment

Comparisons to Prior Studies—This study confirmed that phototherapy is equally effective for older and younger adults, with approximately 90% reaching medium to high clearance levels with approximately 35 treatments in both groups. Prior studies of all age groups found that patients typically cleared with an average of 20 to 28 treatments.^7,8,14-16 In contrast, the findings in older adults from this study were similar to the older adult study from the United Kingdom that reported a 91% clear/near clear rate with an average of 30 treatments.¹⁷ The clearance level also was similar to the older adult study in Turkey¹⁸ that reported 73.7% (70/95) of patients with psoriasis achieved a minimum psoriasis area severity index of 75, indicating 75% improvement from baseline.

Impact of Photosensitizing Medications on Clearance—Photosensitizing medications and treatment frequency were 2 factors that might explain the slower clearance rates in younger adults. In this study, both groups of patients used similar numbers of photosensitizing medications, but more older adults were taking 3 or more medications (Table 3). We found no statistically significant relationship between taking photosensitizing medications and either the clearance rates or the level of clearance achieved in either age group.

Impact of Treatment Frequency—Weekly treatment frequency also was examined. One prior study demonstrated that treatments 3 times weekly led to a faster clearance time and higher clearance levels compared with twice-weekly treatment.⁷ When patients completed treatments twice weekly, it took an average of 1.5 times more days to clear, which impacted cost and clinical resource availability. The patients ranged in age from 17 to 80 years, but outcomes in older patients were not described separately.⁷ Interestingly, our study seemed to find a difference between age groups when the impact of treatment frequency was examined. Older adults completed nearly 4 fewer mean treatments to clear when treating less often, with more than 80% achieving high levels of clearance, whereas the younger adults required almost 7 more treatments to clear when they came in less frequently, with approximately 80% achieving a high level of clearance. As a result, our study found that in both age groups, slowing the treatment frequency extended the treatment time to clearance—more for the younger adults than the older adults—but did not significantly change the percentage of individuals reaching full clearance in either group.

Erythema Rates—There was no association between photosensitizing medications and erythema rates except when patients were taking at least 3 medications. Most medications that listed photosensitivity as a possible side effect did not specify their relevant range of UV radiation; therefore, all such medications were examined during this analysis. Prior research has shown UVB range photosensitizing medications include thiazides, quinidine, calcium channel antagonists, phenothiazines, and nonsteroidal anti-inflammatory drugs.¹⁹ A sensitivity analysis that focused only on these medications found no association between them and any particular grade of erythema. However, patients taking 3 or more of any medications listing photosensitivity as a side effect had an increased risk for grade 2 erythema.

Erythema rates in this study were consistent with a 2013 systematic review that reported 57% of patients with asymptomatic grade 1 erythema.²⁵ In the 2 other comparative older adult studies, erythema rates varied widely: 35% in a study from Turkey¹⁸compared to only1.89% in a study from the United Kingdom.¹⁷

The starting dose for NB-UVB may drive erythema rates. The current study’s protocols were based on an estimated MED that is subjectively determined by the dermatology provider’s assessment of the patient’s skin sensitivity via examination and questions to the patient about their response to environmental sun exposure (ie, burning and tanning)²⁶ and is frequently used to determine the starting dose and subsequent dose escalation. Certain medications have been found to increase photosensitivity and erythema,²⁰ which can change an individual’s MED. If photosensitizing medications are started prior to or during a course of NB-UVB without a pretreatment MED, they might increase the risk for erythema. This study did not identify specific erythema-inducing medications but did find that taking 3 or more photosensitizing medications was associated with increased episodes of grade 2 erythema. Similarly, Harrop et al⁸ found that patients who were taking photosensitizing medications were more likely to have grade 2 or higher erythema, despite baseline MED testing, which is an established safety mechanism to reduce the risk and severity of erythema.^14,20,27 The authors of a recent study of older adults in Taiwan specifically recommended MED testing due to the unpredictable influence of polypharmacy on MED calculations in this population.²⁸ Therefore, this study’s use of an estimated MED in older adults may have influenced the starting dose as well as the incidence and severity of erythemic events. Age-related skin changes likely are ruled out as a consideration for mild erythema by the similarity of grade 1 erythema rates in both older and younger adults. Other studies have identified differences between the age groups, where older patients experienced more intense erythema in the late phase of UVB treatments.^22,23 This phenomenon could increase the risk for a grade 2 erythema, which may correspond with this study’s findings.

Other potential causes of erythema were ruled out during our study, including erythema related to missed treatments and shielding mishaps. Other factors, however, may impact the level of sensitivity each patient has to phototherapy, including genetics, epigenetics, and cumulative sun damage. With NB-UVB, near-erythemogenic doses are optimal to achieve effective treatments but require a delicate balance to achieve, which may be more problematic for older adults, especially those taking several medications.

Study Limitations—Our study design made it difficult to draw conclusions about rarer dermatologic conditions. Some patients received treatments over years that were not included in the study period. Finally, power calculations suggested that our actual sample size was too small, with approximately one-third of the required sample missing.

Practical Implications—The goals of phototherapy are to achieve a high level of disease clearance with the fewest number of treatments possible and minimal side effects. Skin phototype–driven standardized doses based on estimated MED may be conservatively low to minimize the risk of side effects (eg, erythema), which could slow the treatment progression. Thus, basing the starting dose on individual MED assessments may improve clearance rates. This study also confirmed that phototherapy is safe with minimal erythema in adults of all ages. The erythema episodes that patients experienced were few and mild, but because of greater rates of grade 2 erythema in patients on 3 or more photosensitizing medications, consideration of MED testing in both age groups might optimize doses at baseline and prompt caution for subsequent dose titration in this subset of patients.

The extra staff training and patient monitoring required for MED testing likely is to add value and preserve resources if faster clearance rates could be achieved and may warrant further investigation. Phototherapy centers require standardized treatment protocols, diligent well-trained staff, and program monitoring to ensure consistent care to all patients. This study highlighted the ongoing opportunity for health care organizations to conduct evidence-based practice inquiries to continually optimize care for their patients.

Even with recent pharmacologic treatment advances, narrowband UVB (NB-UVB) phototherapy remains a versatile, safe, and efficacious adjunctive or exclusive treatment for multiple dermatologic conditions, including psoriasis and atopic dermatitis. ^1-9 Some providers choose NB-UVB phototherapy as a first-line treatment for older adult patients who frequently use multiple treatment modalities for more than 1 health condition. Older adults with atopic dermatitis and psoriasis are at higher risk for comorbidities such as autoimmune disorders, diabetes mellitus, dyslipidemia, sleep disorders, neuropsychiatric disorders, and cardiovascular disease that can complicate treatment compared with their peers without these dermatologic diagnoses. ^10-12 Polypharmacy (ie, the use of 5 or more daily medications), frequently associated with these conditions, contributes to prescribers pursuing NB-UVB phototherapy as a nonpharmacologic treatment, but some providers wonder if it is as effective and safe for their older patients compared with younger patients.

In a prior study, Matthews et al¹³ reported that 96% (50/52) of patients older than 65 years achieved medium to high levels of clearance with NB-UVB phototherapy. Nonetheless, 2 other findings in this study related to the number of treatments required to achieve clearance (ie, clearance rates) and erythema rates prompted further investigation. The first finding was higher-than-expected clearance rates. Older adults had a clearance rate with a mean of 33 treatments compared to prior studies featuring mean clearance rates of 20 to 28 treatments.^7,8,14-16 This finding resembled a study in the United Kingdom¹⁷ with a median clearance rate in older adults of 30 treatments. In contrast, the median clearance rate from a study in Turkey¹⁸ was 42 treatments in older adults. We hypothesized that more photosensitizing medications used in older vs younger adults prompted more dose adjustments with NB-UVB phototherapy to avoid burning (ie, erythema) at baseline and throughout the treatment course. These dose adjustments may have increased the overall clearance rates. If true, we predicted that younger adults treated with the same protocol would have cleared more quickly, either because of age-related differences or because they likely had fewer comorbidities and therefore fewer medications.

The second finding from Matthews et al¹³ that warranted further investigation was a higher erythema rate compared to the older adult study from the United Kingdom.¹⁷ We hypothesized that potentially greater use of photosensitizing medications in the United States could explain the higher erythema rates. Although medication-induced photosensitivity is less likely with NB-UVB phototherapy than with UVA, certain medications can cause UVB photosensitivity, including thiazides, quinidine, calcium channel antagonists, phenothiazines, and nonsteroidal anti-inflammatory drugs.^8,19,20 Therefore, photosensitizing medication use either at baseline or during a course of NB-UVB phototherapy could increase the risk for erythema. Age-related skin changes also have been considered as a potential cause for erythema. One study found that the skin of older patients was more sensitive than younger patients, resulting in a lower minimal erythema dose (MED)¹⁴—the lowest UV dose that results in erythema.²¹ Others, however, found similar MEDs across age groups, but older adults experienced more intense erythema in the late phase of NB-UVB treatment.^22,23 Such conflicting findings indicate that questions remain regarding the risk for erythema in older patients and if photosensitizing medications are responsible for an increased risk.

This retrospective study aimed to determine if NB-UVB phototherapy is equally effective in both older and younger adults treated with the same protocol; to examine the association between the use of photosensitizing medications and clearance rates in both older and younger adults; and to examine the association between the use of photosensitizing medications and erythema rates in older vs younger adults.

Methods

Study Design and Patients—This retrospective cohort study used billing records to identify patients who received NB-UVB phototherapy at 3 different clinical sites within a large US health care system in Washington (Group Health Cooperative, now Kaiser Permanente Washington), serving more than 600,000 patients between January 1, 2012, and December 31, 2016. The institutional review board of Kaiser Permanente Washington Health Research Institute approved this study (IRB 1498087-4). Younger adults were classified as those 64 years or younger and older adults as those 65 years and older at the start of their phototherapy regimen. A power analysis determined that the optimal sample size for this study was 250 patients.

Individuals were excluded if they had fewer than 6 phototherapy treatments; a diagnosis of vitiligo, photosensitivity dermatitis, morphea, or pityriasis rubra pilaris; and/or treatment of the hands or feet only.

Phototherapy Protocol—Using a 48-lamp NB-UVB unit, trained phototherapy nurses provided all treatments following standardized treatment protocols¹³ based on previously published phototherapy guidelines.²⁴ Nurses determined each patient’s disease clearance level using a 3-point clearance scale (high, medium, low).¹³ Each patient’s starting dose was determined based on the estimated MED for their skin phototype. If the patient was using photosensitizing medications, the protocol indicated a need for a decreased starting dose—down 25% to 50%—depending on the presumed level of photosensitivity. All clinical sites used the same protocol, but decisions about adjustments within this range were made by individual registered nurses and dermatologists, which could lead to variability across sites. Protocols also directed nurses to query patients about specific treatment responses, including erythema, tenderness, or itching; how their condition was responding; use of photosensitizing medications; missed treatments; and placement of shielding. Doses were adjusted accordingly.

Statistical Analysis—Data were analyzed using Stata statistical software (StataCorp LLC). Univariate analyses were used to examine the data and identify outliers, bad values, and missing data, as well as to calculate descriptive statistics. Pearson χ² and Fisher exact statistics were used to calculate differences in categorical variables. Linear multivariate regression models and logistic multivariate models were used to examine statistical relationships between variables. Statistical significance was defined as P≤.05.

Results

Patient Characteristics—Medical records were reviewed for 172 patients who received phototherapy between 2012 and 2016. Patients ranged in age from 23 to 91 years, with 102 patients 64 years and younger and 70 patients 65 years and older. Tables 1 and 2 outline the patient characteristics and conditions treated.

Phototherapy Effectiveness—Narrowband UVB phototherapy was found to be equally effective in older vs younger adults, with 82.9% of older adults (n=58) achieving a high level of clearance vs 80.4% (n=82) of younger adults, and 5.7% (n=4) of older adults achieved a medium level of clearance vs 10% (n=10) of younger adults (Table 3). Although older adults had slightly faster clearance rates on average (34.6 vs 37.2 treatments), these differences were not significant.

Photosensitizing Medications, Clearance Levels, and Clearance Rates—There was no significant association between clearance levels and number of photosensitizing medications in either younger (Figure 1) or older (Figure 2) adults. There was a wide range of clearance rates in both groups (Table 3), but no relationship was identified between clearance rates and photosensitizing medications or age (Figure 3). Clinic C had higher overall clearance rates for both age groups compared to the other clinics (Figure 4), but the clearance levels were still equivalent. No consistent pattern emerged indicating that age was a factor for the slower clearance at this site, and no relationship was identified between taking photosensitizing medications and clearance levels (Fisher exact test, P=.467) or clearance rates (t[149]=0.75; P=.45).

Frequency of Treatments and Clearance Rates—Older adults more consistently completed the recommended frequency of treatments—3 times weekly—compared to younger adults (74.3% vs 58.5%). However, all patients who completed 3 treatments per week required a similar number of treatments to clear (older adults, mean [SD]: 35.7 [21.6]; younger adults, mean [SD]: 34.7 [19.0]; P=.85). Among patients completing 2 or fewer treatments per week, older adults required a mean (SD) of only 31 (9.0) treatments to clear vs 41.5 (21.3) treatments to clear for younger adults, but the difference was not statistically significant (P=.08). However, even those with suboptimal frequency ultimately achieved similar clearance levels.

Photosensitizing Medications and Erythema Rates—Many patients in both age groups took medications that listed photosensitivity as a potential side effect (77.1% of older adults and 60.8% of younger adults). Of them, most patients took only 1 or 2 photosensitizing medications. However, significantly more older patients took 3 or more photosensitizing medications (28.6% vs 12.7%; P=.01)(Table 3). Asymptomatic (grade 1) erythema was unrelated to medication use and quite common in all adults (48.6% of older adults and 60.8% of younger adults). Most patients had only a few episodes of grade 1 erythema (mean [SD], 1.2 [2.9] in older adults and 1.6 [2.2] in younger adults). More older adults had grade 2 erythema (28.6%) compared to younger adults (17.6%). Patients using 3 or more photosensitizing medications were twice as likely to experience grade 2 erythema. Grades 3 and 4 erythema were extremely rare; none of the patients stopped phototherapy because they experienced erythema.

Overall, phototherapy nurses adjusted the starting dose according to the phototype-based protocol an average of 69% of the time for patients on medications with photosensitivity listed as a potential side effect. However, the frequency depended significantly on the clinic (clinic A, 24%; clinic B, 92%; clinic C, 87%)(P≤.001). Nurses across all clinics consistently decreased the treatment dose when patients reported starting new photosensitizing medications. Patients with adjusted starting doses had slightly but not significantly higher clearance rates compared to those without (mean, 37.8 vs 35.5; t(104)=0.58; P=.56).

Comment

Comparisons to Prior Studies—This study confirmed that phototherapy is equally effective for older and younger adults, with approximately 90% reaching medium to high clearance levels with approximately 35 treatments in both groups. Prior studies of all age groups found that patients typically cleared with an average of 20 to 28 treatments.^7,8,14-16 In contrast, the findings in older adults from this study were similar to the older adult study from the United Kingdom that reported a 91% clear/near clear rate with an average of 30 treatments.¹⁷ The clearance level also was similar to the older adult study in Turkey¹⁸ that reported 73.7% (70/95) of patients with psoriasis achieved a minimum psoriasis area severity index of 75, indicating 75% improvement from baseline.

Impact of Photosensitizing Medications on Clearance—Photosensitizing medications and treatment frequency were 2 factors that might explain the slower clearance rates in younger adults. In this study, both groups of patients used similar numbers of photosensitizing medications, but more older adults were taking 3 or more medications (Table 3). We found no statistically significant relationship between taking photosensitizing medications and either the clearance rates or the level of clearance achieved in either age group.

Impact of Treatment Frequency—Weekly treatment frequency also was examined. One prior study demonstrated that treatments 3 times weekly led to a faster clearance time and higher clearance levels compared with twice-weekly treatment.⁷ When patients completed treatments twice weekly, it took an average of 1.5 times more days to clear, which impacted cost and clinical resource availability. The patients ranged in age from 17 to 80 years, but outcomes in older patients were not described separately.⁷ Interestingly, our study seemed to find a difference between age groups when the impact of treatment frequency was examined. Older adults completed nearly 4 fewer mean treatments to clear when treating less often, with more than 80% achieving high levels of clearance, whereas the younger adults required almost 7 more treatments to clear when they came in less frequently, with approximately 80% achieving a high level of clearance. As a result, our study found that in both age groups, slowing the treatment frequency extended the treatment time to clearance—more for the younger adults than the older adults—but did not significantly change the percentage of individuals reaching full clearance in either group.

Erythema Rates—There was no association between photosensitizing medications and erythema rates except when patients were taking at least 3 medications. Most medications that listed photosensitivity as a possible side effect did not specify their relevant range of UV radiation; therefore, all such medications were examined during this analysis. Prior research has shown UVB range photosensitizing medications include thiazides, quinidine, calcium channel antagonists, phenothiazines, and nonsteroidal anti-inflammatory drugs.¹⁹ A sensitivity analysis that focused only on these medications found no association between them and any particular grade of erythema. However, patients taking 3 or more of any medications listing photosensitivity as a side effect had an increased risk for grade 2 erythema.

Erythema rates in this study were consistent with a 2013 systematic review that reported 57% of patients with asymptomatic grade 1 erythema.²⁵ In the 2 other comparative older adult studies, erythema rates varied widely: 35% in a study from Turkey¹⁸compared to only1.89% in a study from the United Kingdom.¹⁷

The starting dose for NB-UVB may drive erythema rates. The current study’s protocols were based on an estimated MED that is subjectively determined by the dermatology provider’s assessment of the patient’s skin sensitivity via examination and questions to the patient about their response to environmental sun exposure (ie, burning and tanning)²⁶ and is frequently used to determine the starting dose and subsequent dose escalation. Certain medications have been found to increase photosensitivity and erythema,²⁰ which can change an individual’s MED. If photosensitizing medications are started prior to or during a course of NB-UVB without a pretreatment MED, they might increase the risk for erythema. This study did not identify specific erythema-inducing medications but did find that taking 3 or more photosensitizing medications was associated with increased episodes of grade 2 erythema. Similarly, Harrop et al⁸ found that patients who were taking photosensitizing medications were more likely to have grade 2 or higher erythema, despite baseline MED testing, which is an established safety mechanism to reduce the risk and severity of erythema.^14,20,27 The authors of a recent study of older adults in Taiwan specifically recommended MED testing due to the unpredictable influence of polypharmacy on MED calculations in this population.²⁸ Therefore, this study’s use of an estimated MED in older adults may have influenced the starting dose as well as the incidence and severity of erythemic events. Age-related skin changes likely are ruled out as a consideration for mild erythema by the similarity of grade 1 erythema rates in both older and younger adults. Other studies have identified differences between the age groups, where older patients experienced more intense erythema in the late phase of UVB treatments.^22,23 This phenomenon could increase the risk for a grade 2 erythema, which may correspond with this study’s findings.

Other potential causes of erythema were ruled out during our study, including erythema related to missed treatments and shielding mishaps. Other factors, however, may impact the level of sensitivity each patient has to phototherapy, including genetics, epigenetics, and cumulative sun damage. With NB-UVB, near-erythemogenic doses are optimal to achieve effective treatments but require a delicate balance to achieve, which may be more problematic for older adults, especially those taking several medications.

Study Limitations—Our study design made it difficult to draw conclusions about rarer dermatologic conditions. Some patients received treatments over years that were not included in the study period. Finally, power calculations suggested that our actual sample size was too small, with approximately one-third of the required sample missing.

Practical Implications—The goals of phototherapy are to achieve a high level of disease clearance with the fewest number of treatments possible and minimal side effects. Skin phototype–driven standardized doses based on estimated MED may be conservatively low to minimize the risk of side effects (eg, erythema), which could slow the treatment progression. Thus, basing the starting dose on individual MED assessments may improve clearance rates. This study also confirmed that phototherapy is safe with minimal erythema in adults of all ages. The erythema episodes that patients experienced were few and mild, but because of greater rates of grade 2 erythema in patients on 3 or more photosensitizing medications, consideration of MED testing in both age groups might optimize doses at baseline and prompt caution for subsequent dose titration in this subset of patients.

The extra staff training and patient monitoring required for MED testing likely is to add value and preserve resources if faster clearance rates could be achieved and may warrant further investigation. Phototherapy centers require standardized treatment protocols, diligent well-trained staff, and program monitoring to ensure consistent care to all patients. This study highlighted the ongoing opportunity for health care organizations to conduct evidence-based practice inquiries to continually optimize care for their patients.

Even with recent pharmacologic treatment advances, narrowband UVB (NB-UVB) phototherapy remains a versatile, safe, and efficacious adjunctive or exclusive treatment for multiple dermatologic conditions, including psoriasis and atopic dermatitis. ^1-9 Some providers choose NB-UVB phototherapy as a first-line treatment for older adult patients who frequently use multiple treatment modalities for more than 1 health condition. Older adults with atopic dermatitis and psoriasis are at higher risk for comorbidities such as autoimmune disorders, diabetes mellitus, dyslipidemia, sleep disorders, neuropsychiatric disorders, and cardiovascular disease that can complicate treatment compared with their peers without these dermatologic diagnoses. ^10-12 Polypharmacy (ie, the use of 5 or more daily medications), frequently associated with these conditions, contributes to prescribers pursuing NB-UVB phototherapy as a nonpharmacologic treatment, but some providers wonder if it is as effective and safe for their older patients compared with younger patients.

In a prior study, Matthews et al¹³ reported that 96% (50/52) of patients older than 65 years achieved medium to high levels of clearance with NB-UVB phototherapy. Nonetheless, 2 other findings in this study related to the number of treatments required to achieve clearance (ie, clearance rates) and erythema rates prompted further investigation. The first finding was higher-than-expected clearance rates. Older adults had a clearance rate with a mean of 33 treatments compared to prior studies featuring mean clearance rates of 20 to 28 treatments.^7,8,14-16 This finding resembled a study in the United Kingdom¹⁷ with a median clearance rate in older adults of 30 treatments. In contrast, the median clearance rate from a study in Turkey¹⁸ was 42 treatments in older adults. We hypothesized that more photosensitizing medications used in older vs younger adults prompted more dose adjustments with NB-UVB phototherapy to avoid burning (ie, erythema) at baseline and throughout the treatment course. These dose adjustments may have increased the overall clearance rates. If true, we predicted that younger adults treated with the same protocol would have cleared more quickly, either because of age-related differences or because they likely had fewer comorbidities and therefore fewer medications.

The second finding from Matthews et al¹³ that warranted further investigation was a higher erythema rate compared to the older adult study from the United Kingdom.¹⁷ We hypothesized that potentially greater use of photosensitizing medications in the United States could explain the higher erythema rates. Although medication-induced photosensitivity is less likely with NB-UVB phototherapy than with UVA, certain medications can cause UVB photosensitivity, including thiazides, quinidine, calcium channel antagonists, phenothiazines, and nonsteroidal anti-inflammatory drugs.^8,19,20 Therefore, photosensitizing medication use either at baseline or during a course of NB-UVB phototherapy could increase the risk for erythema. Age-related skin changes also have been considered as a potential cause for erythema. One study found that the skin of older patients was more sensitive than younger patients, resulting in a lower minimal erythema dose (MED)¹⁴—the lowest UV dose that results in erythema.²¹ Others, however, found similar MEDs across age groups, but older adults experienced more intense erythema in the late phase of NB-UVB treatment.^22,23 Such conflicting findings indicate that questions remain regarding the risk for erythema in older patients and if photosensitizing medications are responsible for an increased risk.

This retrospective study aimed to determine if NB-UVB phototherapy is equally effective in both older and younger adults treated with the same protocol; to examine the association between the use of photosensitizing medications and clearance rates in both older and younger adults; and to examine the association between the use of photosensitizing medications and erythema rates in older vs younger adults.

Methods

Study Design and Patients—This retrospective cohort study used billing records to identify patients who received NB-UVB phototherapy at 3 different clinical sites within a large US health care system in Washington (Group Health Cooperative, now Kaiser Permanente Washington), serving more than 600,000 patients between January 1, 2012, and December 31, 2016. The institutional review board of Kaiser Permanente Washington Health Research Institute approved this study (IRB 1498087-4). Younger adults were classified as those 64 years or younger and older adults as those 65 years and older at the start of their phototherapy regimen. A power analysis determined that the optimal sample size for this study was 250 patients.

Individuals were excluded if they had fewer than 6 phototherapy treatments; a diagnosis of vitiligo, photosensitivity dermatitis, morphea, or pityriasis rubra pilaris; and/or treatment of the hands or feet only.

Phototherapy Protocol—Using a 48-lamp NB-UVB unit, trained phototherapy nurses provided all treatments following standardized treatment protocols¹³ based on previously published phototherapy guidelines.²⁴ Nurses determined each patient’s disease clearance level using a 3-point clearance scale (high, medium, low).¹³ Each patient’s starting dose was determined based on the estimated MED for their skin phototype. If the patient was using photosensitizing medications, the protocol indicated a need for a decreased starting dose—down 25% to 50%—depending on the presumed level of photosensitivity. All clinical sites used the same protocol, but decisions about adjustments within this range were made by individual registered nurses and dermatologists, which could lead to variability across sites. Protocols also directed nurses to query patients about specific treatment responses, including erythema, tenderness, or itching; how their condition was responding; use of photosensitizing medications; missed treatments; and placement of shielding. Doses were adjusted accordingly.

Statistical Analysis—Data were analyzed using Stata statistical software (StataCorp LLC). Univariate analyses were used to examine the data and identify outliers, bad values, and missing data, as well as to calculate descriptive statistics. Pearson χ² and Fisher exact statistics were used to calculate differences in categorical variables. Linear multivariate regression models and logistic multivariate models were used to examine statistical relationships between variables. Statistical significance was defined as P≤.05.

Results

Patient Characteristics—Medical records were reviewed for 172 patients who received phototherapy between 2012 and 2016. Patients ranged in age from 23 to 91 years, with 102 patients 64 years and younger and 70 patients 65 years and older. Tables 1 and 2 outline the patient characteristics and conditions treated.

Phototherapy Effectiveness—Narrowband UVB phototherapy was found to be equally effective in older vs younger adults, with 82.9% of older adults (n=58) achieving a high level of clearance vs 80.4% (n=82) of younger adults, and 5.7% (n=4) of older adults achieved a medium level of clearance vs 10% (n=10) of younger adults (Table 3). Although older adults had slightly faster clearance rates on average (34.6 vs 37.2 treatments), these differences were not significant.

Photosensitizing Medications, Clearance Levels, and Clearance Rates—There was no significant association between clearance levels and number of photosensitizing medications in either younger (Figure 1) or older (Figure 2) adults. There was a wide range of clearance rates in both groups (Table 3), but no relationship was identified between clearance rates and photosensitizing medications or age (Figure 3). Clinic C had higher overall clearance rates for both age groups compared to the other clinics (Figure 4), but the clearance levels were still equivalent. No consistent pattern emerged indicating that age was a factor for the slower clearance at this site, and no relationship was identified between taking photosensitizing medications and clearance levels (Fisher exact test, P=.467) or clearance rates (t[149]=0.75; P=.45).

Frequency of Treatments and Clearance Rates—Older adults more consistently completed the recommended frequency of treatments—3 times weekly—compared to younger adults (74.3% vs 58.5%). However, all patients who completed 3 treatments per week required a similar number of treatments to clear (older adults, mean [SD]: 35.7 [21.6]; younger adults, mean [SD]: 34.7 [19.0]; P=.85). Among patients completing 2 or fewer treatments per week, older adults required a mean (SD) of only 31 (9.0) treatments to clear vs 41.5 (21.3) treatments to clear for younger adults, but the difference was not statistically significant (P=.08). However, even those with suboptimal frequency ultimately achieved similar clearance levels.

Photosensitizing Medications and Erythema Rates—Many patients in both age groups took medications that listed photosensitivity as a potential side effect (77.1% of older adults and 60.8% of younger adults). Of them, most patients took only 1 or 2 photosensitizing medications. However, significantly more older patients took 3 or more photosensitizing medications (28.6% vs 12.7%; P=.01)(Table 3). Asymptomatic (grade 1) erythema was unrelated to medication use and quite common in all adults (48.6% of older adults and 60.8% of younger adults). Most patients had only a few episodes of grade 1 erythema (mean [SD], 1.2 [2.9] in older adults and 1.6 [2.2] in younger adults). More older adults had grade 2 erythema (28.6%) compared to younger adults (17.6%). Patients using 3 or more photosensitizing medications were twice as likely to experience grade 2 erythema. Grades 3 and 4 erythema were extremely rare; none of the patients stopped phototherapy because they experienced erythema.

Overall, phototherapy nurses adjusted the starting dose according to the phototype-based protocol an average of 69% of the time for patients on medications with photosensitivity listed as a potential side effect. However, the frequency depended significantly on the clinic (clinic A, 24%; clinic B, 92%; clinic C, 87%)(P≤.001). Nurses across all clinics consistently decreased the treatment dose when patients reported starting new photosensitizing medications. Patients with adjusted starting doses had slightly but not significantly higher clearance rates compared to those without (mean, 37.8 vs 35.5; t(104)=0.58; P=.56).

Comment

Comparisons to Prior Studies—This study confirmed that phototherapy is equally effective for older and younger adults, with approximately 90% reaching medium to high clearance levels with approximately 35 treatments in both groups. Prior studies of all age groups found that patients typically cleared with an average of 20 to 28 treatments.^7,8,14-16 In contrast, the findings in older adults from this study were similar to the older adult study from the United Kingdom that reported a 91% clear/near clear rate with an average of 30 treatments.¹⁷ The clearance level also was similar to the older adult study in Turkey¹⁸ that reported 73.7% (70/95) of patients with psoriasis achieved a minimum psoriasis area severity index of 75, indicating 75% improvement from baseline.

Impact of Photosensitizing Medications on Clearance—Photosensitizing medications and treatment frequency were 2 factors that might explain the slower clearance rates in younger adults. In this study, both groups of patients used similar numbers of photosensitizing medications, but more older adults were taking 3 or more medications (Table 3). We found no statistically significant relationship between taking photosensitizing medications and either the clearance rates or the level of clearance achieved in either age group.

Impact of Treatment Frequency—Weekly treatment frequency also was examined. One prior study demonstrated that treatments 3 times weekly led to a faster clearance time and higher clearance levels compared with twice-weekly treatment.⁷ When patients completed treatments twice weekly, it took an average of 1.5 times more days to clear, which impacted cost and clinical resource availability. The patients ranged in age from 17 to 80 years, but outcomes in older patients were not described separately.⁷ Interestingly, our study seemed to find a difference between age groups when the impact of treatment frequency was examined. Older adults completed nearly 4 fewer mean treatments to clear when treating less often, with more than 80% achieving high levels of clearance, whereas the younger adults required almost 7 more treatments to clear when they came in less frequently, with approximately 80% achieving a high level of clearance. As a result, our study found that in both age groups, slowing the treatment frequency extended the treatment time to clearance—more for the younger adults than the older adults—but did not significantly change the percentage of individuals reaching full clearance in either group.

Erythema Rates—There was no association between photosensitizing medications and erythema rates except when patients were taking at least 3 medications. Most medications that listed photosensitivity as a possible side effect did not specify their relevant range of UV radiation; therefore, all such medications were examined during this analysis. Prior research has shown UVB range photosensitizing medications include thiazides, quinidine, calcium channel antagonists, phenothiazines, and nonsteroidal anti-inflammatory drugs.¹⁹ A sensitivity analysis that focused only on these medications found no association between them and any particular grade of erythema. However, patients taking 3 or more of any medications listing photosensitivity as a side effect had an increased risk for grade 2 erythema.

Erythema rates in this study were consistent with a 2013 systematic review that reported 57% of patients with asymptomatic grade 1 erythema.²⁵ In the 2 other comparative older adult studies, erythema rates varied widely: 35% in a study from Turkey¹⁸compared to only1.89% in a study from the United Kingdom.¹⁷

The starting dose for NB-UVB may drive erythema rates. The current study’s protocols were based on an estimated MED that is subjectively determined by the dermatology provider’s assessment of the patient’s skin sensitivity via examination and questions to the patient about their response to environmental sun exposure (ie, burning and tanning)²⁶ and is frequently used to determine the starting dose and subsequent dose escalation. Certain medications have been found to increase photosensitivity and erythema,²⁰ which can change an individual’s MED. If photosensitizing medications are started prior to or during a course of NB-UVB without a pretreatment MED, they might increase the risk for erythema. This study did not identify specific erythema-inducing medications but did find that taking 3 or more photosensitizing medications was associated with increased episodes of grade 2 erythema. Similarly, Harrop et al⁸ found that patients who were taking photosensitizing medications were more likely to have grade 2 or higher erythema, despite baseline MED testing, which is an established safety mechanism to reduce the risk and severity of erythema.^14,20,27 The authors of a recent study of older adults in Taiwan specifically recommended MED testing due to the unpredictable influence of polypharmacy on MED calculations in this population.²⁸ Therefore, this study’s use of an estimated MED in older adults may have influenced the starting dose as well as the incidence and severity of erythemic events. Age-related skin changes likely are ruled out as a consideration for mild erythema by the similarity of grade 1 erythema rates in both older and younger adults. Other studies have identified differences between the age groups, where older patients experienced more intense erythema in the late phase of UVB treatments.^22,23 This phenomenon could increase the risk for a grade 2 erythema, which may correspond with this study’s findings.

Other potential causes of erythema were ruled out during our study, including erythema related to missed treatments and shielding mishaps. Other factors, however, may impact the level of sensitivity each patient has to phototherapy, including genetics, epigenetics, and cumulative sun damage. With NB-UVB, near-erythemogenic doses are optimal to achieve effective treatments but require a delicate balance to achieve, which may be more problematic for older adults, especially those taking several medications.

Study Limitations—Our study design made it difficult to draw conclusions about rarer dermatologic conditions. Some patients received treatments over years that were not included in the study period. Finally, power calculations suggested that our actual sample size was too small, with approximately one-third of the required sample missing.

Practical Implications—The goals of phototherapy are to achieve a high level of disease clearance with the fewest number of treatments possible and minimal side effects. Skin phototype–driven standardized doses based on estimated MED may be conservatively low to minimize the risk of side effects (eg, erythema), which could slow the treatment progression. Thus, basing the starting dose on individual MED assessments may improve clearance rates. This study also confirmed that phototherapy is safe with minimal erythema in adults of all ages. The erythema episodes that patients experienced were few and mild, but because of greater rates of grade 2 erythema in patients on 3 or more photosensitizing medications, consideration of MED testing in both age groups might optimize doses at baseline and prompt caution for subsequent dose titration in this subset of patients.

The extra staff training and patient monitoring required for MED testing likely is to add value and preserve resources if faster clearance rates could be achieved and may warrant further investigation. Phototherapy centers require standardized treatment protocols, diligent well-trained staff, and program monitoring to ensure consistent care to all patients. This study highlighted the ongoing opportunity for health care organizations to conduct evidence-based practice inquiries to continually optimize care for their patients.

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

A version of this article first appeared on Medscape.com.

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

A version of this article first appeared on Medscape.com.

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

A version of this article first appeared on Medscape.com.

Patients with prurigo nodularis (PN) who had severe itch and high lesion counts and whose condition was inadequately controlled with prior therapies experienced significant improvements with dupilumab (Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.

The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.

More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.

The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.

Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”

Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.

The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.

Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.

He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).

Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).

With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.

Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.

Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.

The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.

A version of this article first appeared on Medscape.com.

Patients with prurigo nodularis (PN) who had severe itch and high lesion counts and whose condition was inadequately controlled with prior therapies experienced significant improvements with dupilumab (Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.

The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.

More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.

The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.

Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”

Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.

The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.

Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.

He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).

Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).

With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.

Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.

Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.

The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.

A version of this article first appeared on Medscape.com.

Patients with prurigo nodularis (PN) who had severe itch and high lesion counts and whose condition was inadequately controlled with prior therapies experienced significant improvements with dupilumab (Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.

The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.

More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.

The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.

Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”

Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.

The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.

Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.

He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).

Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).

With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.

Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.

Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.

The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.

A version of this article first appeared on Medscape.com.

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 common inflammatory skin conditions that may have similar clinical presentations. Historically, it was thought that these conditions could not be diagnosed simultaneously due to their differing immune mechanisms; however, this belief has been challenged by recent evidence suggesting a more nuanced relationship between the 2 disease processes. In this review, we examine the complex interplay between AD and ACD and explain how shifts in conventional understanding of the 2 conditions shaped our evolving recognition of their ability to coexist.

Epidemiology of AD and ACD

Atopic dermatitis is the most common inflammatory skin disease in children and adolescents, with an estimated prevalence reaching 21%.¹ In 60% of cases, onset of AD will occur within the first year of life, and 90% of cases begin within the first 5 years.² Resolution may occur by adulthood; however, AD may continue to impact up to 8% to 9% of adults, with an increased prevalence in those older than 75 years.¹ This may represent an underestimation of the burden of adult AD; one systematic review of 17 studies found that the pooled proportion of adult-onset AD was greater than 25%.³

In contrast, ACD previously was assumed to be a disease that more commonly impacted adults and only rarely children, primarily due to an early misconception that children were not frequently exposed to contact allergens and their immune systems were too immature to react to them even if exposed.^4,5 However, it is now known that children do have risk factors for development of ACD, including a thinner stratum corneum and potentially a more absorbent skin surface.⁴ In addition, a 2022 study by the North American Contact Dermatitis Group (NACDG) found similar rates of ACD in children (n=1871) and adults (n=41,699) referred for patch testing (55.2% and 57.3%, respectively) as well as similar rates of having at least 1 relevant positive patch test (49.2% and 52.2%).⁶

In opposition to traditional beliefs, these findings highlight that AD and ACD can occur across age groups.

Immune Mechanism

The pathogenesis of AD represents a multifactorial process involving the immune system, cutaneous flora, genetic predisposition, and surrounding environment. Immunologically, acute AD is driven by a predominantly T_H2 helper T-cell response with high levels of IL-4, IL-5, and IL-13⁷; T_H22, T_H17, and T_H1 also have been implicated.⁸ Notably, T_H17 is found in high levels during the acute eczema phase, while T_H1 and T_H22are associated with the chronic phase.⁷

The pathophysiology of ACD is not completely understood. The classic paradigm involves 2 phases: sensitization and elicitation. Sensitization involves antigen-presenting cells that take up allergens absorbed by the skin to present them in regional lymph nodes where antigen-specific T lymphocytes are generated. Elicitation occurs upon re-exposure to the allergen, at which time the primed T lymphocytes are recruited to the skin, causing inflammation.⁹ Allergic contact dermatitis initially was thought to be driven by T_H1 cytokines and IL-17 but now is understood to be more complex.¹⁰ Studies have revealed immune polarization of contact allergens, demonstrating that nickel primarily induces a T_H1/T_H17 response, whereas fragrance and rubber accelerators skew to T_H2; T_H9 and T_H22 also may be involved depending on the causative allergen.^11,12

Of note, the immunologic differences between AD and ACD led early investigators to believe that patients with AD were relatively protected from ACD.¹³ However, as previously described, there are several overlapping cytokines between AD and ACD. Furthermore, research has revealed that risk of contact sensitization might be increased in the chronic eczema phase due to the shared T_H1 pathway.¹⁴ Barrier-disrupted skin (such as that in AD) also may increase the cytokine response and the density of antigen-presenting cells, leading to a proallergic state.¹⁵ This suggests that the immunologic pathways of AD and ACD are more intertwined than was previously understood.

Underlying Risk Factors

Skin barrier dysfunction is a key step in the pathogenesis of AD. Patients with AD commonly have loss-of-function mutations in the filaggrin gene, a protein that is key to the function of the stratum corneum. Loss of this protein may not only impact the immune response as previously noted but also may lead to increased transepidermal water loss and bacterial colonization.¹⁶ Interestingly, a 2014 review examined how this mutation could lead to an increased risk of sensitization to bivalent metal ions via an impaired chelating ability of the skin.¹⁷ Furthermore, a 2016 study conducted in Dutch construction workers revealed an increased risk for contact dermatitis (irritant and allergic) for those with a loss-of-function filaggrin mutation.¹⁸

Importantly, this same mutation may explain why patients with AD tend to have increased skin colonization by Staphylococcus aureus. The abundance of S aureus and the relative decrease in the diversity of other microorganisms on the skin may be associated with increased AD severity.¹⁹ Likewise, S aureus may play a role in the pathogenesis of ACD via production of its exotoxin directed at the T-cell receptor V beta 17 region. In particular, this receptor has been associated with nickel sensitization.¹⁷

Another risk factor to consider is increased exposure to contact sensitizers when treating AD. For instance, management often includes use of over-the-counter emollients, natural or botanical remedies with purported benefits for AD, cleansers, and detergents. However, these products can contain some of the most prevalent contact allergens seen in those with AD, including methyl-isothiazolinone, formaldehyde releasers, and fragrance.²⁰ Topical corticosteroids also are frequently used, and ACD to steroid molecules can occur, particularly to tixocortol-21-pivalate (a marker for class A corticosteroids) and budesonide (a marker for class B corticosteroids).²¹ Other allergens (eg, benzyl alcohol, propylene glycol) also may be found as inactive ingredients of topical corticosteroids.²² These exposures may place AD patients at risk for ACD.

The Coexistence of AD and ACD

Given the overlapping epidemiology, immunology, and potentially increased risk for the development of ACD in patients with AD, it would be reasonable to assume that the 2 diagnoses could coexist; however, is there clinical data to support this idea? Based on recent database reviews, the answer appears to be yes.^20,23-26 An analysis from the Pediatric Contact Dermatitis Registry revealed that 30% of 1142 pediatric patch test cases analyzed were diagnosed as AD and ACD simultaneously.²⁴ The NACDG found similar results in its 2021 review, as 29.5% of children (n=1648) and 20.7% of adults (n=36,834) had a concurrent diagnosis of AD and ACD.²⁰ Notably, older results from these databases also demonstrated an association between the 2 conditions.^23,25,26

It remains unclear whether the prevalence of ACD is higher in those with or without AD. A comprehensive systematic review conducted in 2017 examined this topic through analysis of 74 studies. The results demonstrated a similar prevalence of contact sensitization in individuals with and without AD.²⁷ Another systematic review of 31 studies conducted in 2017 found a higher prevalence for ACD in children without AD; however, the authors noted that the included studies were too variable (eg, size, design, allergens tested) to draw definitive conclusions.²⁸

Even though there is no clear overall increased risk for ACD in patients with AD, research has suggested that certain allergens may be more prevalent in the setting of AD. An NACDG study found that adults with AD had increased odds of reacting to 10 of the top 25 NACDG screening allergens compared to those without AD.²⁰ Other studies have found that AD patients may be more likely to become sensitized to certain allergens, such as fragrance and lanolin.¹⁴

Considerations for Management

Diagnosis of ACD in patients with AD can be challenging because these conditions may present similarly with chronic, pruritic, inflammatory patches and plaques. Chronic ACD may be misdiagnosed as AD if patch testing is not performed.²⁹ Given the prevalence of ACD in the setting of AD, there should be a low threshold to pursue patch testing, especially when dermatitis is recalcitrant to standard therapies or presents in an atypical distribution (ie, perioral, predominantly head/neck, hand and foot, isolated eyelid involvement, buttocks).^4,30 Various allergen series are available for patch testing adults and children including the NACDG Standard Series, American Contact Dermatitis Society Core Allergen Series, or the Pediatric Baseline Series.^31-33

If potentially relevant allergens are uncovered by patch testing, patients should be counseled on avoidance strategies. However, allergen avoidance may not always lead to complete symptom resolution, especially if AD is present concomitantly with ACD. Therefore, use of topical or systemic therapies still may be required. Topical corticosteroids can be used when dermatitis is acute and localized. Systemic corticosteroids are utilized for both diagnoses when cases are more severe or extensive, but their adverse-effect profile limits long-term use. Other systemic treatments, including conventional agents (ie, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil), biologics, and small molecule inhibitors also may be considered for severe cases.^34,35 Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved for use in moderate to severe AD in patients 6 months and older. Recent evidence has suggested that dupilumab also may be an effective off-label treatment choice for ACD when allergen avoidance alone is insufficient.³⁶ Studies have been conducted on secukinumab, a monoclonal antibody against IL-17; however, it has not been shown to be effective in either AD or ACD.^37,38 This indicates that targeted biologics may not always be successful in treating these diagnoses, likely due to their complex immune pathways. Finally, there is an emerging role for JAK inhibitors. Three are approved for AD: topical ruxolitinib, oral abrocitinib, and oral upadacitinib.³⁹ Further investigation is needed to determine the efficacy of JAK inhibitors in ACD.

Final Interpretation

Evolving evidence shows that AD and ACD can occur at the same time despite the historical perspective that their immune pathways were too polarized for this to happen. Atopic dermatitis may be an important risk factor for subsequent development of ACD. Management should include a low threshold to perform patch testing, while pharmacotherapies utilized in the treatment of both conditions should be considered.

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 common inflammatory skin conditions that may have similar clinical presentations. Historically, it was thought that these conditions could not be diagnosed simultaneously due to their differing immune mechanisms; however, this belief has been challenged by recent evidence suggesting a more nuanced relationship between the 2 disease processes. In this review, we examine the complex interplay between AD and ACD and explain how shifts in conventional understanding of the 2 conditions shaped our evolving recognition of their ability to coexist.

Epidemiology of AD and ACD

Atopic dermatitis is the most common inflammatory skin disease in children and adolescents, with an estimated prevalence reaching 21%.¹ In 60% of cases, onset of AD will occur within the first year of life, and 90% of cases begin within the first 5 years.² Resolution may occur by adulthood; however, AD may continue to impact up to 8% to 9% of adults, with an increased prevalence in those older than 75 years.¹ This may represent an underestimation of the burden of adult AD; one systematic review of 17 studies found that the pooled proportion of adult-onset AD was greater than 25%.³

In contrast, ACD previously was assumed to be a disease that more commonly impacted adults and only rarely children, primarily due to an early misconception that children were not frequently exposed to contact allergens and their immune systems were too immature to react to them even if exposed.^4,5 However, it is now known that children do have risk factors for development of ACD, including a thinner stratum corneum and potentially a more absorbent skin surface.⁴ In addition, a 2022 study by the North American Contact Dermatitis Group (NACDG) found similar rates of ACD in children (n=1871) and adults (n=41,699) referred for patch testing (55.2% and 57.3%, respectively) as well as similar rates of having at least 1 relevant positive patch test (49.2% and 52.2%).⁶

In opposition to traditional beliefs, these findings highlight that AD and ACD can occur across age groups.

Immune Mechanism

The pathogenesis of AD represents a multifactorial process involving the immune system, cutaneous flora, genetic predisposition, and surrounding environment. Immunologically, acute AD is driven by a predominantly T_H2 helper T-cell response with high levels of IL-4, IL-5, and IL-13⁷; T_H22, T_H17, and T_H1 also have been implicated.⁸ Notably, T_H17 is found in high levels during the acute eczema phase, while T_H1 and T_H22are associated with the chronic phase.⁷

The pathophysiology of ACD is not completely understood. The classic paradigm involves 2 phases: sensitization and elicitation. Sensitization involves antigen-presenting cells that take up allergens absorbed by the skin to present them in regional lymph nodes where antigen-specific T lymphocytes are generated. Elicitation occurs upon re-exposure to the allergen, at which time the primed T lymphocytes are recruited to the skin, causing inflammation.⁹ Allergic contact dermatitis initially was thought to be driven by T_H1 cytokines and IL-17 but now is understood to be more complex.¹⁰ Studies have revealed immune polarization of contact allergens, demonstrating that nickel primarily induces a T_H1/T_H17 response, whereas fragrance and rubber accelerators skew to T_H2; T_H9 and T_H22 also may be involved depending on the causative allergen.^11,12

Of note, the immunologic differences between AD and ACD led early investigators to believe that patients with AD were relatively protected from ACD.¹³ However, as previously described, there are several overlapping cytokines between AD and ACD. Furthermore, research has revealed that risk of contact sensitization might be increased in the chronic eczema phase due to the shared T_H1 pathway.¹⁴ Barrier-disrupted skin (such as that in AD) also may increase the cytokine response and the density of antigen-presenting cells, leading to a proallergic state.¹⁵ This suggests that the immunologic pathways of AD and ACD are more intertwined than was previously understood.

Underlying Risk Factors

Skin barrier dysfunction is a key step in the pathogenesis of AD. Patients with AD commonly have loss-of-function mutations in the filaggrin gene, a protein that is key to the function of the stratum corneum. Loss of this protein may not only impact the immune response as previously noted but also may lead to increased transepidermal water loss and bacterial colonization.¹⁶ Interestingly, a 2014 review examined how this mutation could lead to an increased risk of sensitization to bivalent metal ions via an impaired chelating ability of the skin.¹⁷ Furthermore, a 2016 study conducted in Dutch construction workers revealed an increased risk for contact dermatitis (irritant and allergic) for those with a loss-of-function filaggrin mutation.¹⁸

Importantly, this same mutation may explain why patients with AD tend to have increased skin colonization by Staphylococcus aureus. The abundance of S aureus and the relative decrease in the diversity of other microorganisms on the skin may be associated with increased AD severity.¹⁹ Likewise, S aureus may play a role in the pathogenesis of ACD via production of its exotoxin directed at the T-cell receptor V beta 17 region. In particular, this receptor has been associated with nickel sensitization.¹⁷

Another risk factor to consider is increased exposure to contact sensitizers when treating AD. For instance, management often includes use of over-the-counter emollients, natural or botanical remedies with purported benefits for AD, cleansers, and detergents. However, these products can contain some of the most prevalent contact allergens seen in those with AD, including methyl-isothiazolinone, formaldehyde releasers, and fragrance.²⁰ Topical corticosteroids also are frequently used, and ACD to steroid molecules can occur, particularly to tixocortol-21-pivalate (a marker for class A corticosteroids) and budesonide (a marker for class B corticosteroids).²¹ Other allergens (eg, benzyl alcohol, propylene glycol) also may be found as inactive ingredients of topical corticosteroids.²² These exposures may place AD patients at risk for ACD.

The Coexistence of AD and ACD

Given the overlapping epidemiology, immunology, and potentially increased risk for the development of ACD in patients with AD, it would be reasonable to assume that the 2 diagnoses could coexist; however, is there clinical data to support this idea? Based on recent database reviews, the answer appears to be yes.^20,23-26 An analysis from the Pediatric Contact Dermatitis Registry revealed that 30% of 1142 pediatric patch test cases analyzed were diagnosed as AD and ACD simultaneously.²⁴ The NACDG found similar results in its 2021 review, as 29.5% of children (n=1648) and 20.7% of adults (n=36,834) had a concurrent diagnosis of AD and ACD.²⁰ Notably, older results from these databases also demonstrated an association between the 2 conditions.^23,25,26

It remains unclear whether the prevalence of ACD is higher in those with or without AD. A comprehensive systematic review conducted in 2017 examined this topic through analysis of 74 studies. The results demonstrated a similar prevalence of contact sensitization in individuals with and without AD.²⁷ Another systematic review of 31 studies conducted in 2017 found a higher prevalence for ACD in children without AD; however, the authors noted that the included studies were too variable (eg, size, design, allergens tested) to draw definitive conclusions.²⁸

Even though there is no clear overall increased risk for ACD in patients with AD, research has suggested that certain allergens may be more prevalent in the setting of AD. An NACDG study found that adults with AD had increased odds of reacting to 10 of the top 25 NACDG screening allergens compared to those without AD.²⁰ Other studies have found that AD patients may be more likely to become sensitized to certain allergens, such as fragrance and lanolin.¹⁴

Considerations for Management

Diagnosis of ACD in patients with AD can be challenging because these conditions may present similarly with chronic, pruritic, inflammatory patches and plaques. Chronic ACD may be misdiagnosed as AD if patch testing is not performed.²⁹ Given the prevalence of ACD in the setting of AD, there should be a low threshold to pursue patch testing, especially when dermatitis is recalcitrant to standard therapies or presents in an atypical distribution (ie, perioral, predominantly head/neck, hand and foot, isolated eyelid involvement, buttocks).^4,30 Various allergen series are available for patch testing adults and children including the NACDG Standard Series, American Contact Dermatitis Society Core Allergen Series, or the Pediatric Baseline Series.^31-33

If potentially relevant allergens are uncovered by patch testing, patients should be counseled on avoidance strategies. However, allergen avoidance may not always lead to complete symptom resolution, especially if AD is present concomitantly with ACD. Therefore, use of topical or systemic therapies still may be required. Topical corticosteroids can be used when dermatitis is acute and localized. Systemic corticosteroids are utilized for both diagnoses when cases are more severe or extensive, but their adverse-effect profile limits long-term use. Other systemic treatments, including conventional agents (ie, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil), biologics, and small molecule inhibitors also may be considered for severe cases.^34,35 Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved for use in moderate to severe AD in patients 6 months and older. Recent evidence has suggested that dupilumab also may be an effective off-label treatment choice for ACD when allergen avoidance alone is insufficient.³⁶ Studies have been conducted on secukinumab, a monoclonal antibody against IL-17; however, it has not been shown to be effective in either AD or ACD.^37,38 This indicates that targeted biologics may not always be successful in treating these diagnoses, likely due to their complex immune pathways. Finally, there is an emerging role for JAK inhibitors. Three are approved for AD: topical ruxolitinib, oral abrocitinib, and oral upadacitinib.³⁹ Further investigation is needed to determine the efficacy of JAK inhibitors in ACD.

Final Interpretation

Evolving evidence shows that AD and ACD can occur at the same time despite the historical perspective that their immune pathways were too polarized for this to happen. Atopic dermatitis may be an important risk factor for subsequent development of ACD. Management should include a low threshold to perform patch testing, while pharmacotherapies utilized in the treatment of both conditions should be considered.

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 common inflammatory skin conditions that may have similar clinical presentations. Historically, it was thought that these conditions could not be diagnosed simultaneously due to their differing immune mechanisms; however, this belief has been challenged by recent evidence suggesting a more nuanced relationship between the 2 disease processes. In this review, we examine the complex interplay between AD and ACD and explain how shifts in conventional understanding of the 2 conditions shaped our evolving recognition of their ability to coexist.

Epidemiology of AD and ACD

Atopic dermatitis is the most common inflammatory skin disease in children and adolescents, with an estimated prevalence reaching 21%.¹ In 60% of cases, onset of AD will occur within the first year of life, and 90% of cases begin within the first 5 years.² Resolution may occur by adulthood; however, AD may continue to impact up to 8% to 9% of adults, with an increased prevalence in those older than 75 years.¹ This may represent an underestimation of the burden of adult AD; one systematic review of 17 studies found that the pooled proportion of adult-onset AD was greater than 25%.³

In contrast, ACD previously was assumed to be a disease that more commonly impacted adults and only rarely children, primarily due to an early misconception that children were not frequently exposed to contact allergens and their immune systems were too immature to react to them even if exposed.^4,5 However, it is now known that children do have risk factors for development of ACD, including a thinner stratum corneum and potentially a more absorbent skin surface.⁴ In addition, a 2022 study by the North American Contact Dermatitis Group (NACDG) found similar rates of ACD in children (n=1871) and adults (n=41,699) referred for patch testing (55.2% and 57.3%, respectively) as well as similar rates of having at least 1 relevant positive patch test (49.2% and 52.2%).⁶

In opposition to traditional beliefs, these findings highlight that AD and ACD can occur across age groups.

Immune Mechanism

The pathogenesis of AD represents a multifactorial process involving the immune system, cutaneous flora, genetic predisposition, and surrounding environment. Immunologically, acute AD is driven by a predominantly T_H2 helper T-cell response with high levels of IL-4, IL-5, and IL-13⁷; T_H22, T_H17, and T_H1 also have been implicated.⁸ Notably, T_H17 is found in high levels during the acute eczema phase, while T_H1 and T_H22are associated with the chronic phase.⁷

The pathophysiology of ACD is not completely understood. The classic paradigm involves 2 phases: sensitization and elicitation. Sensitization involves antigen-presenting cells that take up allergens absorbed by the skin to present them in regional lymph nodes where antigen-specific T lymphocytes are generated. Elicitation occurs upon re-exposure to the allergen, at which time the primed T lymphocytes are recruited to the skin, causing inflammation.⁹ Allergic contact dermatitis initially was thought to be driven by T_H1 cytokines and IL-17 but now is understood to be more complex.¹⁰ Studies have revealed immune polarization of contact allergens, demonstrating that nickel primarily induces a T_H1/T_H17 response, whereas fragrance and rubber accelerators skew to T_H2; T_H9 and T_H22 also may be involved depending on the causative allergen.^11,12

Of note, the immunologic differences between AD and ACD led early investigators to believe that patients with AD were relatively protected from ACD.¹³ However, as previously described, there are several overlapping cytokines between AD and ACD. Furthermore, research has revealed that risk of contact sensitization might be increased in the chronic eczema phase due to the shared T_H1 pathway.¹⁴ Barrier-disrupted skin (such as that in AD) also may increase the cytokine response and the density of antigen-presenting cells, leading to a proallergic state.¹⁵ This suggests that the immunologic pathways of AD and ACD are more intertwined than was previously understood.

Underlying Risk Factors

Skin barrier dysfunction is a key step in the pathogenesis of AD. Patients with AD commonly have loss-of-function mutations in the filaggrin gene, a protein that is key to the function of the stratum corneum. Loss of this protein may not only impact the immune response as previously noted but also may lead to increased transepidermal water loss and bacterial colonization.¹⁶ Interestingly, a 2014 review examined how this mutation could lead to an increased risk of sensitization to bivalent metal ions via an impaired chelating ability of the skin.¹⁷ Furthermore, a 2016 study conducted in Dutch construction workers revealed an increased risk for contact dermatitis (irritant and allergic) for those with a loss-of-function filaggrin mutation.¹⁸

Importantly, this same mutation may explain why patients with AD tend to have increased skin colonization by Staphylococcus aureus. The abundance of S aureus and the relative decrease in the diversity of other microorganisms on the skin may be associated with increased AD severity.¹⁹ Likewise, S aureus may play a role in the pathogenesis of ACD via production of its exotoxin directed at the T-cell receptor V beta 17 region. In particular, this receptor has been associated with nickel sensitization.¹⁷

Another risk factor to consider is increased exposure to contact sensitizers when treating AD. For instance, management often includes use of over-the-counter emollients, natural or botanical remedies with purported benefits for AD, cleansers, and detergents. However, these products can contain some of the most prevalent contact allergens seen in those with AD, including methyl-isothiazolinone, formaldehyde releasers, and fragrance.²⁰ Topical corticosteroids also are frequently used, and ACD to steroid molecules can occur, particularly to tixocortol-21-pivalate (a marker for class A corticosteroids) and budesonide (a marker for class B corticosteroids).²¹ Other allergens (eg, benzyl alcohol, propylene glycol) also may be found as inactive ingredients of topical corticosteroids.²² These exposures may place AD patients at risk for ACD.

The Coexistence of AD and ACD

Given the overlapping epidemiology, immunology, and potentially increased risk for the development of ACD in patients with AD, it would be reasonable to assume that the 2 diagnoses could coexist; however, is there clinical data to support this idea? Based on recent database reviews, the answer appears to be yes.^20,23-26 An analysis from the Pediatric Contact Dermatitis Registry revealed that 30% of 1142 pediatric patch test cases analyzed were diagnosed as AD and ACD simultaneously.²⁴ The NACDG found similar results in its 2021 review, as 29.5% of children (n=1648) and 20.7% of adults (n=36,834) had a concurrent diagnosis of AD and ACD.²⁰ Notably, older results from these databases also demonstrated an association between the 2 conditions.^23,25,26

It remains unclear whether the prevalence of ACD is higher in those with or without AD. A comprehensive systematic review conducted in 2017 examined this topic through analysis of 74 studies. The results demonstrated a similar prevalence of contact sensitization in individuals with and without AD.²⁷ Another systematic review of 31 studies conducted in 2017 found a higher prevalence for ACD in children without AD; however, the authors noted that the included studies were too variable (eg, size, design, allergens tested) to draw definitive conclusions.²⁸

Even though there is no clear overall increased risk for ACD in patients with AD, research has suggested that certain allergens may be more prevalent in the setting of AD. An NACDG study found that adults with AD had increased odds of reacting to 10 of the top 25 NACDG screening allergens compared to those without AD.²⁰ Other studies have found that AD patients may be more likely to become sensitized to certain allergens, such as fragrance and lanolin.¹⁴

Considerations for Management

Diagnosis of ACD in patients with AD can be challenging because these conditions may present similarly with chronic, pruritic, inflammatory patches and plaques. Chronic ACD may be misdiagnosed as AD if patch testing is not performed.²⁹ Given the prevalence of ACD in the setting of AD, there should be a low threshold to pursue patch testing, especially when dermatitis is recalcitrant to standard therapies or presents in an atypical distribution (ie, perioral, predominantly head/neck, hand and foot, isolated eyelid involvement, buttocks).^4,30 Various allergen series are available for patch testing adults and children including the NACDG Standard Series, American Contact Dermatitis Society Core Allergen Series, or the Pediatric Baseline Series.^31-33

If potentially relevant allergens are uncovered by patch testing, patients should be counseled on avoidance strategies. However, allergen avoidance may not always lead to complete symptom resolution, especially if AD is present concomitantly with ACD. Therefore, use of topical or systemic therapies still may be required. Topical corticosteroids can be used when dermatitis is acute and localized. Systemic corticosteroids are utilized for both diagnoses when cases are more severe or extensive, but their adverse-effect profile limits long-term use. Other systemic treatments, including conventional agents (ie, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil), biologics, and small molecule inhibitors also may be considered for severe cases.^34,35 Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved for use in moderate to severe AD in patients 6 months and older. Recent evidence has suggested that dupilumab also may be an effective off-label treatment choice for ACD when allergen avoidance alone is insufficient.³⁶ Studies have been conducted on secukinumab, a monoclonal antibody against IL-17; however, it has not been shown to be effective in either AD or ACD.^37,38 This indicates that targeted biologics may not always be successful in treating these diagnoses, likely due to their complex immune pathways. Finally, there is an emerging role for JAK inhibitors. Three are approved for AD: topical ruxolitinib, oral abrocitinib, and oral upadacitinib.³⁹ Further investigation is needed to determine the efficacy of JAK inhibitors in ACD.

Final Interpretation

Evolving evidence shows that AD and ACD can occur at the same time despite the historical perspective that their immune pathways were too polarized for this to happen. Atopic dermatitis may be an important risk factor for subsequent development of ACD. Management should include a low threshold to perform patch testing, while pharmacotherapies utilized in the treatment of both conditions should be considered.

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.