Clinical Edge Journal Scan

The use of proton pump inhibitors (PPI) can affect the bioavailability and effectiveness of concomitant medications, including cancer therapies. A retrospective study by Lee and colleagues aimed to identify the clinical outcomes of patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative advanced or metastatic BC who were concomitantly using PPI and palbociclib. The study included 1310 patients, of which 344 received concomitant PPI plus palbociclib and 966 patients received palbociclib alone. Results showed that patients who received concomitant PPI plus palbociclib had significantly shorter progression-free survival (hazard ratio 1.76; 95% CI 1.46-2.13) and overall survival (hazard ratio 2.72; 95% CI 2.07-3.53) rates compared with those who received palbociclib alone. These results suggest that the concomitant use of PPI with palbociclib may alter the therapeutic efficacy of the drug. More research studies are needed to confirm these findings.

Pfeiler and colleagues examined the association of BMI with side effects, treatment discontinuation, and efficacy of palbociclib. This study looked at 5698 patients with early-stage HR+ BC who received palbociclib plus endocrine therapy as part of a preplanned analysis of the PALLAS trial. Results showed that in women who received adjuvant palbociclib, higher BMI was associated with a significantly lower rate of neutropenia (odds ratio for a 1-unit change in BMI 0.93; 95% CI 0.92-0.95) and a lower rate of treatment discontinuation (adjusted hazard ratio for a 10-unit change in BMI 0.75; 95% CI 0.67-0.83) compared with normal-weight patients. No effect of BMI on palbociclib efficacy was observed at 31 months of follow-up. Further studies are needed to validate these findings in different cohorts.

In cases of early-stage breast cancer (clinical T1, T2) where patients undergo upfront breast-conserving therapy and sentinel lymph node biopsy (SLNB), completion of axillary lymph node dissection (CLND) is often omitted if only one or two positive sentinel lymph nodes are detected. A study by Zaveri and colleagues looked at outcomes among 548 patients with cT1-2 N0 BC who were treated with upfront mastectomy and had one or two positive lymph nodes on SLNB. The 5-year cumulative incidence rate of overall locoregional recurrence was comparable between patients who underwent vs those who did not undergo CLND (1.8% vs 1.3%; P = .93); receipt of post-mastectomy radiation therapy did not affect the locoregional recurrence rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638). These results suggest that CLND may not necessarily improve outcomes in this patient population. Larger prospective studies are needed to confirm these findings.

The use of proton pump inhibitors (PPI) can affect the bioavailability and effectiveness of concomitant medications, including cancer therapies. A retrospective study by Lee and colleagues aimed to identify the clinical outcomes of patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative advanced or metastatic BC who were concomitantly using PPI and palbociclib. The study included 1310 patients, of which 344 received concomitant PPI plus palbociclib and 966 patients received palbociclib alone. Results showed that patients who received concomitant PPI plus palbociclib had significantly shorter progression-free survival (hazard ratio 1.76; 95% CI 1.46-2.13) and overall survival (hazard ratio 2.72; 95% CI 2.07-3.53) rates compared with those who received palbociclib alone. These results suggest that the concomitant use of PPI with palbociclib may alter the therapeutic efficacy of the drug. More research studies are needed to confirm these findings.

Pfeiler and colleagues examined the association of BMI with side effects, treatment discontinuation, and efficacy of palbociclib. This study looked at 5698 patients with early-stage HR+ BC who received palbociclib plus endocrine therapy as part of a preplanned analysis of the PALLAS trial. Results showed that in women who received adjuvant palbociclib, higher BMI was associated with a significantly lower rate of neutropenia (odds ratio for a 1-unit change in BMI 0.93; 95% CI 0.92-0.95) and a lower rate of treatment discontinuation (adjusted hazard ratio for a 10-unit change in BMI 0.75; 95% CI 0.67-0.83) compared with normal-weight patients. No effect of BMI on palbociclib efficacy was observed at 31 months of follow-up. Further studies are needed to validate these findings in different cohorts.

In cases of early-stage breast cancer (clinical T1, T2) where patients undergo upfront breast-conserving therapy and sentinel lymph node biopsy (SLNB), completion of axillary lymph node dissection (CLND) is often omitted if only one or two positive sentinel lymph nodes are detected. A study by Zaveri and colleagues looked at outcomes among 548 patients with cT1-2 N0 BC who were treated with upfront mastectomy and had one or two positive lymph nodes on SLNB. The 5-year cumulative incidence rate of overall locoregional recurrence was comparable between patients who underwent vs those who did not undergo CLND (1.8% vs 1.3%; P = .93); receipt of post-mastectomy radiation therapy did not affect the locoregional recurrence rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638). These results suggest that CLND may not necessarily improve outcomes in this patient population. Larger prospective studies are needed to confirm these findings.

The use of proton pump inhibitors (PPI) can affect the bioavailability and effectiveness of concomitant medications, including cancer therapies. A retrospective study by Lee and colleagues aimed to identify the clinical outcomes of patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative advanced or metastatic BC who were concomitantly using PPI and palbociclib. The study included 1310 patients, of which 344 received concomitant PPI plus palbociclib and 966 patients received palbociclib alone. Results showed that patients who received concomitant PPI plus palbociclib had significantly shorter progression-free survival (hazard ratio 1.76; 95% CI 1.46-2.13) and overall survival (hazard ratio 2.72; 95% CI 2.07-3.53) rates compared with those who received palbociclib alone. These results suggest that the concomitant use of PPI with palbociclib may alter the therapeutic efficacy of the drug. More research studies are needed to confirm these findings.

Pfeiler and colleagues examined the association of BMI with side effects, treatment discontinuation, and efficacy of palbociclib. This study looked at 5698 patients with early-stage HR+ BC who received palbociclib plus endocrine therapy as part of a preplanned analysis of the PALLAS trial. Results showed that in women who received adjuvant palbociclib, higher BMI was associated with a significantly lower rate of neutropenia (odds ratio for a 1-unit change in BMI 0.93; 95% CI 0.92-0.95) and a lower rate of treatment discontinuation (adjusted hazard ratio for a 10-unit change in BMI 0.75; 95% CI 0.67-0.83) compared with normal-weight patients. No effect of BMI on palbociclib efficacy was observed at 31 months of follow-up. Further studies are needed to validate these findings in different cohorts.

In cases of early-stage breast cancer (clinical T1, T2) where patients undergo upfront breast-conserving therapy and sentinel lymph node biopsy (SLNB), completion of axillary lymph node dissection (CLND) is often omitted if only one or two positive sentinel lymph nodes are detected. A study by Zaveri and colleagues looked at outcomes among 548 patients with cT1-2 N0 BC who were treated with upfront mastectomy and had one or two positive lymph nodes on SLNB. The 5-year cumulative incidence rate of overall locoregional recurrence was comparable between patients who underwent vs those who did not undergo CLND (1.8% vs 1.3%; P = .93); receipt of post-mastectomy radiation therapy did not affect the locoregional recurrence rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638). These results suggest that CLND may not necessarily improve outcomes in this patient population. Larger prospective studies are needed to confirm these findings.

Although the usual age at onset of PsA is in the fourth or fifth decade of life, children may develop juvenile-onset PsA (JPsA). Less attention has been paid to this form of juvenile idiopathic arthritis (JIA), and the impact of JPsA vis-à-vis other forms of JIA is not well known. In addition, only about half of the patients with JPsA have cutaneous psoriasis. The impact of psoriasis on children with JPsA is not known. In order to evaluate differences in disease outcomes in patients with JPsA, Low and colleagues evaluated 1653 children and young people with JIA who were recruited to the Childhood Arthritis Prospective Study, of whom 111 had JPsA at diagnosis. They demonstrated that there were no significant differences in patient-reported outcomes between children with JPsA and other JIA categories. However, children with JPsA and psoriasis at JPsA diagnosis had more depressive symptoms compared with those without psoriasis. Moreover, children with JPsA vs other JIA categories had 2.35 times higher odds of having persistently poor well-being scores despite improvements in joint counts and physician global scores. Thus, children with JPsA have poorer well-being scores and a higher prevalence of depression, which requires multidisciplinary care.

Apart from immunomodulatory therapies, weight loss leads to improvement in disease activity in patients with obesity and PsA. However, the mechanisms by which weight loss improves PsA is currently not known, but is likely to be due to changes in adipokines and inflammation-related cytokines. In a recent study¹that included patients with PsA and obesity, it was demonstrated that weight loss through a Very Low Energy Diet (VLED) resulted in significant improvements in PsA disease activity. Landgren and colleagues now aimed to determine the effects of VLED on cytokines and adipokines. They obtained blood samples from patients with PsA and obesity (n = 41) and matched control individuals without rheumatic disease or psoriasis (n = 39) who were on VLED. At month 6, along with significant weight loss, serum levels of interleukin-23 and leptin decreased significantly, while those of total adiponectin and high-molecular-weight adiponectin increased significantly in patients with PsA and control individuals. The change in body mass index correlated positively with a reduction in serum interleukin-23 (r_S = 0.671, P < .001) and improvement in PsA disease activity (P = .003). This study highlights the anti-inflammatory effect of weight loss in patients with PsA. Weight loss can complement immunomodulatory therapy in PsA patients with obesity.

Additional Reference

1. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21:17. doi: 10.1186/s13075-019-1810-5

Although the usual age at onset of PsA is in the fourth or fifth decade of life, children may develop juvenile-onset PsA (JPsA). Less attention has been paid to this form of juvenile idiopathic arthritis (JIA), and the impact of JPsA vis-à-vis other forms of JIA is not well known. In addition, only about half of the patients with JPsA have cutaneous psoriasis. The impact of psoriasis on children with JPsA is not known. In order to evaluate differences in disease outcomes in patients with JPsA, Low and colleagues evaluated 1653 children and young people with JIA who were recruited to the Childhood Arthritis Prospective Study, of whom 111 had JPsA at diagnosis. They demonstrated that there were no significant differences in patient-reported outcomes between children with JPsA and other JIA categories. However, children with JPsA and psoriasis at JPsA diagnosis had more depressive symptoms compared with those without psoriasis. Moreover, children with JPsA vs other JIA categories had 2.35 times higher odds of having persistently poor well-being scores despite improvements in joint counts and physician global scores. Thus, children with JPsA have poorer well-being scores and a higher prevalence of depression, which requires multidisciplinary care.

Apart from immunomodulatory therapies, weight loss leads to improvement in disease activity in patients with obesity and PsA. However, the mechanisms by which weight loss improves PsA is currently not known, but is likely to be due to changes in adipokines and inflammation-related cytokines. In a recent study¹that included patients with PsA and obesity, it was demonstrated that weight loss through a Very Low Energy Diet (VLED) resulted in significant improvements in PsA disease activity. Landgren and colleagues now aimed to determine the effects of VLED on cytokines and adipokines. They obtained blood samples from patients with PsA and obesity (n = 41) and matched control individuals without rheumatic disease or psoriasis (n = 39) who were on VLED. At month 6, along with significant weight loss, serum levels of interleukin-23 and leptin decreased significantly, while those of total adiponectin and high-molecular-weight adiponectin increased significantly in patients with PsA and control individuals. The change in body mass index correlated positively with a reduction in serum interleukin-23 (r_S = 0.671, P < .001) and improvement in PsA disease activity (P = .003). This study highlights the anti-inflammatory effect of weight loss in patients with PsA. Weight loss can complement immunomodulatory therapy in PsA patients with obesity.

Additional Reference

1. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21:17. doi: 10.1186/s13075-019-1810-5

Although the usual age at onset of PsA is in the fourth or fifth decade of life, children may develop juvenile-onset PsA (JPsA). Less attention has been paid to this form of juvenile idiopathic arthritis (JIA), and the impact of JPsA vis-à-vis other forms of JIA is not well known. In addition, only about half of the patients with JPsA have cutaneous psoriasis. The impact of psoriasis on children with JPsA is not known. In order to evaluate differences in disease outcomes in patients with JPsA, Low and colleagues evaluated 1653 children and young people with JIA who were recruited to the Childhood Arthritis Prospective Study, of whom 111 had JPsA at diagnosis. They demonstrated that there were no significant differences in patient-reported outcomes between children with JPsA and other JIA categories. However, children with JPsA and psoriasis at JPsA diagnosis had more depressive symptoms compared with those without psoriasis. Moreover, children with JPsA vs other JIA categories had 2.35 times higher odds of having persistently poor well-being scores despite improvements in joint counts and physician global scores. Thus, children with JPsA have poorer well-being scores and a higher prevalence of depression, which requires multidisciplinary care.

Apart from immunomodulatory therapies, weight loss leads to improvement in disease activity in patients with obesity and PsA. However, the mechanisms by which weight loss improves PsA is currently not known, but is likely to be due to changes in adipokines and inflammation-related cytokines. In a recent study¹that included patients with PsA and obesity, it was demonstrated that weight loss through a Very Low Energy Diet (VLED) resulted in significant improvements in PsA disease activity. Landgren and colleagues now aimed to determine the effects of VLED on cytokines and adipokines. They obtained blood samples from patients with PsA and obesity (n = 41) and matched control individuals without rheumatic disease or psoriasis (n = 39) who were on VLED. At month 6, along with significant weight loss, serum levels of interleukin-23 and leptin decreased significantly, while those of total adiponectin and high-molecular-weight adiponectin increased significantly in patients with PsA and control individuals. The change in body mass index correlated positively with a reduction in serum interleukin-23 (r_S = 0.671, P < .001) and improvement in PsA disease activity (P = .003). This study highlights the anti-inflammatory effect of weight loss in patients with PsA. Weight loss can complement immunomodulatory therapy in PsA patients with obesity.

Additional Reference

1. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21:17. doi: 10.1186/s13075-019-1810-5

Amlitelimab is a monoclonal antibody that targets the OX40 ligand (Weidinger et al). It is predicted to have broad potential therapeutic application for multiple immune diseases, including atopic dermatitis. I'm not looking for that. I've been spoiled by drugs that have narrow therapeutic application (like IL-23 blockade and IL-4/IL-13 blockade) that target a specific disease very effectively with very little in the way of side effects.

The OX40 ligand/receptor interaction may be too important. When I Google "OX40 deficiency," the first thing that pops up is a combined T- and B-cell immunodeficiency associated with possible aggressive, childhood-onset, disseminated, cutaneous, and systemic Kaposi sarcoma. That doesn't mean that such a horrible outcome will come with the level of pharmacologic OX40 blockade that we would try to achieve in our patients. Clinical trials don't show horrible adverse events — so far. I'm in no hurry to find out in my patients whether real-life efficacy in large numbers of people treated for long periods of time matches up with the short-term safety profiles seen in relatively small clinical trial populations.

It might be nice to give patients upadacitinib only as needed, for example for a flare of their atopic dermatitis, then cut down the dose or stop altogether until the next flare. The study by Guttman-Yassky and colleagues found that atopic dermatitis came back quickly when upadacitinib was stopped. However, their study looked at patients with chronically bad atopic dermatitis. If we have a patient who tends to flare only intermittently, it may be that we could use upadacitinib or other systemic treatments on an intermittent basis. I know when it came to my son's mild atopic dermatitis, intermittent use of a little triamcinolone ointment was all that was needed. Yes, I know that's a "reactive," roller-coaster approach. Yes, I know that a "proactive" keep-the-disease-away approach sounds better. But I'm realistic when it comes to patients' adherence behaviors. I think there's a lot to be said for minimizing drug exposure and just using treatments as needed. Guttman-Yassky's work makes me believe that a lot of patients will need continuous treatment to keep their severe disease under control. I'm not convinced that everyone will need continuous treatment to be happy with their treatment.

O'Connor and colleagues found that emollient bathing is associated with later development of atopic dermatitis. They defined emollient bathing as baths with oil or emulsifier-based additives. This study illustrates the importance of randomization in a controlled trial. Because their study was not randomized, we don't know whether the emollient bathing caused atopic dermatitis or whether families that had more dry skin or more family history of atopic dermatitis were more likely to use emollient bathing.

When dupilumab was first approved, I prescribed it to my patients to take every 2 weeks as recommended on the label. I'm not so sure how many patients actually used it that way. I suspect that a lot of them took the medicine less often than recommended, especially when they were doing well. This report by Sánchez-García and colleagues suggests that patients who are doing very well on dupilumab may be able to take the drug less often. That's probably not news to my patients who are already taking the drug less often than I told them to.

I think less frequent dosing may become even more common over time, particularly for drugs that may have more safety risks than dupilumab. Many patients with atopic dermatitis probably don't need to be taking drugs all the time. Patients who tend to have flare-ups but who do very well for a long period of time between flares may only need drugs intermittently. It will be interesting to see if our patients can use oral treatments for atopic dermatitis that way.

Siegfried and colleagues assessed how well dupilumab worked in children with atopic dermatitis in different areas of the body: head and neck, trunk, upper extremities, lower extremities. Dupilumab worked well in all these areas, as expected.

Xu and colleagues did a meta-analysis of studies of dupilumab for atopic dermatitis and concluded, not shockingly, that dupilumab is safe and effective for atopic dermatitis. Okay, I believe that. They further concluded: "More long-term, high-quality, controlled studies in different regions are needed for further verification." I don't think so. I think the evidence is clear already.

Studies that measure the levels of things are generally not particularly helpful. The study by García-Reyes and colleagues studied the levels of serum thymic stromal lymphopoietin (TSLP) in patients with atopic dermatitis. TSLP levels were higher in patients with atopic dermatitis compared with patients without atopic dermatitis. This basically tells us nothing about the role of TSLP in atopic dermatitis. The elevated levels could be causing atopic dermatitis or they could be the body's response to having atopic dermatitis.

To tell whether something is causal we have to look at either genetic studies or studies with specific inhibitors. A specific inhibitor study was done by atopic dermatitis expert Eric Simpson and colleagues.1 This was a randomized, placebo-controlled study in which an anti-TSLP antibody was given to patients with atopic dermatitis. Both the anti-TSLP antibody and placebo groups were permitted to use topical steroids. While the anti-TSLP antibody–treated patients did better than placebo-treated patients, the difference did not achieve statistical significance, probably, I believe, because the placebo-treated patients used more topical steroids. When you want to assess whether a drug for atopic dermatitis is better than placebo, you must be careful about how much topical steroid you let patients in the study use!

Additional Reference

1. Simpson EL, Parnes JR, She D, et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. J Am Acad Dermatol. 2019;80(4):1013-1021. doi: 10.1016/j.jaad.2018.11.059

Amlitelimab is a monoclonal antibody that targets the OX40 ligand (Weidinger et al). It is predicted to have broad potential therapeutic application for multiple immune diseases, including atopic dermatitis. I'm not looking for that. I've been spoiled by drugs that have narrow therapeutic application (like IL-23 blockade and IL-4/IL-13 blockade) that target a specific disease very effectively with very little in the way of side effects.

The OX40 ligand/receptor interaction may be too important. When I Google "OX40 deficiency," the first thing that pops up is a combined T- and B-cell immunodeficiency associated with possible aggressive, childhood-onset, disseminated, cutaneous, and systemic Kaposi sarcoma. That doesn't mean that such a horrible outcome will come with the level of pharmacologic OX40 blockade that we would try to achieve in our patients. Clinical trials don't show horrible adverse events — so far. I'm in no hurry to find out in my patients whether real-life efficacy in large numbers of people treated for long periods of time matches up with the short-term safety profiles seen in relatively small clinical trial populations.

It might be nice to give patients upadacitinib only as needed, for example for a flare of their atopic dermatitis, then cut down the dose or stop altogether until the next flare. The study by Guttman-Yassky and colleagues found that atopic dermatitis came back quickly when upadacitinib was stopped. However, their study looked at patients with chronically bad atopic dermatitis. If we have a patient who tends to flare only intermittently, it may be that we could use upadacitinib or other systemic treatments on an intermittent basis. I know when it came to my son's mild atopic dermatitis, intermittent use of a little triamcinolone ointment was all that was needed. Yes, I know that's a "reactive," roller-coaster approach. Yes, I know that a "proactive" keep-the-disease-away approach sounds better. But I'm realistic when it comes to patients' adherence behaviors. I think there's a lot to be said for minimizing drug exposure and just using treatments as needed. Guttman-Yassky's work makes me believe that a lot of patients will need continuous treatment to keep their severe disease under control. I'm not convinced that everyone will need continuous treatment to be happy with their treatment.

O'Connor and colleagues found that emollient bathing is associated with later development of atopic dermatitis. They defined emollient bathing as baths with oil or emulsifier-based additives. This study illustrates the importance of randomization in a controlled trial. Because their study was not randomized, we don't know whether the emollient bathing caused atopic dermatitis or whether families that had more dry skin or more family history of atopic dermatitis were more likely to use emollient bathing.

When dupilumab was first approved, I prescribed it to my patients to take every 2 weeks as recommended on the label. I'm not so sure how many patients actually used it that way. I suspect that a lot of them took the medicine less often than recommended, especially when they were doing well. This report by Sánchez-García and colleagues suggests that patients who are doing very well on dupilumab may be able to take the drug less often. That's probably not news to my patients who are already taking the drug less often than I told them to.

I think less frequent dosing may become even more common over time, particularly for drugs that may have more safety risks than dupilumab. Many patients with atopic dermatitis probably don't need to be taking drugs all the time. Patients who tend to have flare-ups but who do very well for a long period of time between flares may only need drugs intermittently. It will be interesting to see if our patients can use oral treatments for atopic dermatitis that way.

Siegfried and colleagues assessed how well dupilumab worked in children with atopic dermatitis in different areas of the body: head and neck, trunk, upper extremities, lower extremities. Dupilumab worked well in all these areas, as expected.

Xu and colleagues did a meta-analysis of studies of dupilumab for atopic dermatitis and concluded, not shockingly, that dupilumab is safe and effective for atopic dermatitis. Okay, I believe that. They further concluded: "More long-term, high-quality, controlled studies in different regions are needed for further verification." I don't think so. I think the evidence is clear already.

Studies that measure the levels of things are generally not particularly helpful. The study by García-Reyes and colleagues studied the levels of serum thymic stromal lymphopoietin (TSLP) in patients with atopic dermatitis. TSLP levels were higher in patients with atopic dermatitis compared with patients without atopic dermatitis. This basically tells us nothing about the role of TSLP in atopic dermatitis. The elevated levels could be causing atopic dermatitis or they could be the body's response to having atopic dermatitis.

To tell whether something is causal we have to look at either genetic studies or studies with specific inhibitors. A specific inhibitor study was done by atopic dermatitis expert Eric Simpson and colleagues.1 This was a randomized, placebo-controlled study in which an anti-TSLP antibody was given to patients with atopic dermatitis. Both the anti-TSLP antibody and placebo groups were permitted to use topical steroids. While the anti-TSLP antibody–treated patients did better than placebo-treated patients, the difference did not achieve statistical significance, probably, I believe, because the placebo-treated patients used more topical steroids. When you want to assess whether a drug for atopic dermatitis is better than placebo, you must be careful about how much topical steroid you let patients in the study use!

Additional Reference

1. Simpson EL, Parnes JR, She D, et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. J Am Acad Dermatol. 2019;80(4):1013-1021. doi: 10.1016/j.jaad.2018.11.059

Amlitelimab is a monoclonal antibody that targets the OX40 ligand (Weidinger et al). It is predicted to have broad potential therapeutic application for multiple immune diseases, including atopic dermatitis. I'm not looking for that. I've been spoiled by drugs that have narrow therapeutic application (like IL-23 blockade and IL-4/IL-13 blockade) that target a specific disease very effectively with very little in the way of side effects.

The OX40 ligand/receptor interaction may be too important. When I Google "OX40 deficiency," the first thing that pops up is a combined T- and B-cell immunodeficiency associated with possible aggressive, childhood-onset, disseminated, cutaneous, and systemic Kaposi sarcoma. That doesn't mean that such a horrible outcome will come with the level of pharmacologic OX40 blockade that we would try to achieve in our patients. Clinical trials don't show horrible adverse events — so far. I'm in no hurry to find out in my patients whether real-life efficacy in large numbers of people treated for long periods of time matches up with the short-term safety profiles seen in relatively small clinical trial populations.

It might be nice to give patients upadacitinib only as needed, for example for a flare of their atopic dermatitis, then cut down the dose or stop altogether until the next flare. The study by Guttman-Yassky and colleagues found that atopic dermatitis came back quickly when upadacitinib was stopped. However, their study looked at patients with chronically bad atopic dermatitis. If we have a patient who tends to flare only intermittently, it may be that we could use upadacitinib or other systemic treatments on an intermittent basis. I know when it came to my son's mild atopic dermatitis, intermittent use of a little triamcinolone ointment was all that was needed. Yes, I know that's a "reactive," roller-coaster approach. Yes, I know that a "proactive" keep-the-disease-away approach sounds better. But I'm realistic when it comes to patients' adherence behaviors. I think there's a lot to be said for minimizing drug exposure and just using treatments as needed. Guttman-Yassky's work makes me believe that a lot of patients will need continuous treatment to keep their severe disease under control. I'm not convinced that everyone will need continuous treatment to be happy with their treatment.

O'Connor and colleagues found that emollient bathing is associated with later development of atopic dermatitis. They defined emollient bathing as baths with oil or emulsifier-based additives. This study illustrates the importance of randomization in a controlled trial. Because their study was not randomized, we don't know whether the emollient bathing caused atopic dermatitis or whether families that had more dry skin or more family history of atopic dermatitis were more likely to use emollient bathing.

When dupilumab was first approved, I prescribed it to my patients to take every 2 weeks as recommended on the label. I'm not so sure how many patients actually used it that way. I suspect that a lot of them took the medicine less often than recommended, especially when they were doing well. This report by Sánchez-García and colleagues suggests that patients who are doing very well on dupilumab may be able to take the drug less often. That's probably not news to my patients who are already taking the drug less often than I told them to.

I think less frequent dosing may become even more common over time, particularly for drugs that may have more safety risks than dupilumab. Many patients with atopic dermatitis probably don't need to be taking drugs all the time. Patients who tend to have flare-ups but who do very well for a long period of time between flares may only need drugs intermittently. It will be interesting to see if our patients can use oral treatments for atopic dermatitis that way.

Siegfried and colleagues assessed how well dupilumab worked in children with atopic dermatitis in different areas of the body: head and neck, trunk, upper extremities, lower extremities. Dupilumab worked well in all these areas, as expected.

Xu and colleagues did a meta-analysis of studies of dupilumab for atopic dermatitis and concluded, not shockingly, that dupilumab is safe and effective for atopic dermatitis. Okay, I believe that. They further concluded: "More long-term, high-quality, controlled studies in different regions are needed for further verification." I don't think so. I think the evidence is clear already.

Studies that measure the levels of things are generally not particularly helpful. The study by García-Reyes and colleagues studied the levels of serum thymic stromal lymphopoietin (TSLP) in patients with atopic dermatitis. TSLP levels were higher in patients with atopic dermatitis compared with patients without atopic dermatitis. This basically tells us nothing about the role of TSLP in atopic dermatitis. The elevated levels could be causing atopic dermatitis or they could be the body's response to having atopic dermatitis.

To tell whether something is causal we have to look at either genetic studies or studies with specific inhibitors. A specific inhibitor study was done by atopic dermatitis expert Eric Simpson and colleagues.1 This was a randomized, placebo-controlled study in which an anti-TSLP antibody was given to patients with atopic dermatitis. Both the anti-TSLP antibody and placebo groups were permitted to use topical steroids. While the anti-TSLP antibody–treated patients did better than placebo-treated patients, the difference did not achieve statistical significance, probably, I believe, because the placebo-treated patients used more topical steroids. When you want to assess whether a drug for atopic dermatitis is better than placebo, you must be careful about how much topical steroid you let patients in the study use!

Additional Reference

1. Simpson EL, Parnes JR, She D, et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. J Am Acad Dermatol. 2019;80(4):1013-1021. doi: 10.1016/j.jaad.2018.11.059

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

Key clinical point: Serum levels of thymic stromal lymphopoietin (TSLP) are significantly elevated in patients with atopic dermatitis (AD), with the levels being significantly higher in adults than in children and increasing significantly corresponding to the severity of AD.

Major finding: Patients with AD vs control individuals had significantly higher serum levels of TSLP (standardized mean difference [SMD] 2.21; P < .001). Serum TSLP levels were significantly higher in adults vs children with AD (P = .02) and had a significant positive association with AD severity (mild: SMD 1.15; P = .025; moderate: SMD 2.48; P = .024; severe: SMD 8.28; P = .000002).

Study details: The data come from a meta-analysis of 14 studies involving 1032 patients with AD and 416 control individuals without AD.

Disclosures: This study was funded by the Universidad Nacional Autónoma de México. The authors declared no conflicts of interest.

Source: García-Reyes MM et al. Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: A systematic review and meta-analysis. Clin Exp Med. 2023 (Jul 29). doi: 10.1007/s10238-023-01147-5

Key clinical point: Serum levels of thymic stromal lymphopoietin (TSLP) are significantly elevated in patients with atopic dermatitis (AD), with the levels being significantly higher in adults than in children and increasing significantly corresponding to the severity of AD.

Major finding: Patients with AD vs control individuals had significantly higher serum levels of TSLP (standardized mean difference [SMD] 2.21; P < .001). Serum TSLP levels were significantly higher in adults vs children with AD (P = .02) and had a significant positive association with AD severity (mild: SMD 1.15; P = .025; moderate: SMD 2.48; P = .024; severe: SMD 8.28; P = .000002).

Study details: The data come from a meta-analysis of 14 studies involving 1032 patients with AD and 416 control individuals without AD.

Disclosures: This study was funded by the Universidad Nacional Autónoma de México. The authors declared no conflicts of interest.

Source: García-Reyes MM et al. Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: A systematic review and meta-analysis. Clin Exp Med. 2023 (Jul 29). doi: 10.1007/s10238-023-01147-5

Key clinical point: Serum levels of thymic stromal lymphopoietin (TSLP) are significantly elevated in patients with atopic dermatitis (AD), with the levels being significantly higher in adults than in children and increasing significantly corresponding to the severity of AD.

Major finding: Patients with AD vs control individuals had significantly higher serum levels of TSLP (standardized mean difference [SMD] 2.21; P < .001). Serum TSLP levels were significantly higher in adults vs children with AD (P = .02) and had a significant positive association with AD severity (mild: SMD 1.15; P = .025; moderate: SMD 2.48; P = .024; severe: SMD 8.28; P = .000002).

Study details: The data come from a meta-analysis of 14 studies involving 1032 patients with AD and 416 control individuals without AD.

Disclosures: This study was funded by the Universidad Nacional Autónoma de México. The authors declared no conflicts of interest.

Source: García-Reyes MM et al. Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: A systematic review and meta-analysis. Clin Exp Med. 2023 (Jul 29). doi: 10.1007/s10238-023-01147-5

Key clinical point: Dupilumab demonstrates favorable efficacy and manageable safety in pediatric patients with atopic dermatitis (AD), with greater improvements in clinical signs observed with an increase in the treatment duration.

Major finding: The overall pooled Eczema Area and Severity Index (EASI) 75 response rate was 57.4% (95% CI 48.1%-66.2%), whereas an Investigator's Global Assessment score of 0 or 1 was achieved by 35.2% (29.3%-41.5%) of patients. EASI 75 response rates were 26.8% (95% CI 20.7%-33.9%) and 84.9% (95% CI 79.6%-89.0%) after 2-8 weeks and 32-52 weeks of treatment, respectively. Treatment-emergent adverse events were mostly mild-to-moderate in severity.

Study details: This meta-analysis included 18 studies (7 clinical and 11 observational) involving 1275 children and adolescents with AD.

Disclosures: This study was supported by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Xu Y et al. Efficacy and safety profile of dupilumab for the treatment of atopic dermatitis in children and adolescents: A systematic review and meta-analysis. Pediatr Dermatol. 2023 (Aug 2). doi: 10.1111/pde.15398

Key clinical point: Dupilumab demonstrates favorable efficacy and manageable safety in pediatric patients with atopic dermatitis (AD), with greater improvements in clinical signs observed with an increase in the treatment duration.

Major finding: The overall pooled Eczema Area and Severity Index (EASI) 75 response rate was 57.4% (95% CI 48.1%-66.2%), whereas an Investigator's Global Assessment score of 0 or 1 was achieved by 35.2% (29.3%-41.5%) of patients. EASI 75 response rates were 26.8% (95% CI 20.7%-33.9%) and 84.9% (95% CI 79.6%-89.0%) after 2-8 weeks and 32-52 weeks of treatment, respectively. Treatment-emergent adverse events were mostly mild-to-moderate in severity.

Study details: This meta-analysis included 18 studies (7 clinical and 11 observational) involving 1275 children and adolescents with AD.

Disclosures: This study was supported by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Xu Y et al. Efficacy and safety profile of dupilumab for the treatment of atopic dermatitis in children and adolescents: A systematic review and meta-analysis. Pediatr Dermatol. 2023 (Aug 2). doi: 10.1111/pde.15398

Key clinical point: Dupilumab demonstrates favorable efficacy and manageable safety in pediatric patients with atopic dermatitis (AD), with greater improvements in clinical signs observed with an increase in the treatment duration.

Major finding: The overall pooled Eczema Area and Severity Index (EASI) 75 response rate was 57.4% (95% CI 48.1%-66.2%), whereas an Investigator's Global Assessment score of 0 or 1 was achieved by 35.2% (29.3%-41.5%) of patients. EASI 75 response rates were 26.8% (95% CI 20.7%-33.9%) and 84.9% (95% CI 79.6%-89.0%) after 2-8 weeks and 32-52 weeks of treatment, respectively. Treatment-emergent adverse events were mostly mild-to-moderate in severity.

Study details: This meta-analysis included 18 studies (7 clinical and 11 observational) involving 1275 children and adolescents with AD.

Disclosures: This study was supported by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Xu Y et al. Efficacy and safety profile of dupilumab for the treatment of atopic dermatitis in children and adolescents: A systematic review and meta-analysis. Pediatr Dermatol. 2023 (Aug 2). doi: 10.1111/pde.15398

Key clinical point: Reduction in dupilumab dose to every 3 or 4 weeks does not decrease its efficacy in patients with persistently-controlled atopic dermatitis (AD), with clinical outcome measures remaining stable over time.

Major finding: After 144 weeks, similar to patients receiving 300 mg dupilumab every 2 weeks, those receiving 300 mg dupilumab every 3 and 4 weeks had significantly decreased mean Eczema Area and Severity Index, Severity Scoring of Atopic Dermatitis, Pruritus Numerical Rating Scale, and Sleep Numerical Rating Scale scores (all P < .05).

Study details: This multicenter retrospective observational study included 54 patients age ≥ 16 years with controlled moderate-to-severe AD treated with dupilumab for ≥ 1 year who were assigned to receive 300 mg dupilumab every 2 weeks (n = 27), 3 weeks (n = 17), or 4 weeks (n = 10).

Disclosures: This study received no specific funding from any sources. The authors declared no conflicts of interest.

Source: Sánchez-García V et al. Evaluation of dupilumab dosing regimen in patients with persistently controlled atopic dermatitis. J Eur Acad Dermatol Venereol. 2023 (Jul 17). doi: 10.1111/jdv.19348

Key clinical point: Reduction in dupilumab dose to every 3 or 4 weeks does not decrease its efficacy in patients with persistently-controlled atopic dermatitis (AD), with clinical outcome measures remaining stable over time.

Major finding: After 144 weeks, similar to patients receiving 300 mg dupilumab every 2 weeks, those receiving 300 mg dupilumab every 3 and 4 weeks had significantly decreased mean Eczema Area and Severity Index, Severity Scoring of Atopic Dermatitis, Pruritus Numerical Rating Scale, and Sleep Numerical Rating Scale scores (all P < .05).

Study details: This multicenter retrospective observational study included 54 patients age ≥ 16 years with controlled moderate-to-severe AD treated with dupilumab for ≥ 1 year who were assigned to receive 300 mg dupilumab every 2 weeks (n = 27), 3 weeks (n = 17), or 4 weeks (n = 10).

Disclosures: This study received no specific funding from any sources. The authors declared no conflicts of interest.

Source: Sánchez-García V et al. Evaluation of dupilumab dosing regimen in patients with persistently controlled atopic dermatitis. J Eur Acad Dermatol Venereol. 2023 (Jul 17). doi: 10.1111/jdv.19348

Key clinical point: Reduction in dupilumab dose to every 3 or 4 weeks does not decrease its efficacy in patients with persistently-controlled atopic dermatitis (AD), with clinical outcome measures remaining stable over time.

Major finding: After 144 weeks, similar to patients receiving 300 mg dupilumab every 2 weeks, those receiving 300 mg dupilumab every 3 and 4 weeks had significantly decreased mean Eczema Area and Severity Index, Severity Scoring of Atopic Dermatitis, Pruritus Numerical Rating Scale, and Sleep Numerical Rating Scale scores (all P < .05).

Study details: This multicenter retrospective observational study included 54 patients age ≥ 16 years with controlled moderate-to-severe AD treated with dupilumab for ≥ 1 year who were assigned to receive 300 mg dupilumab every 2 weeks (n = 27), 3 weeks (n = 17), or 4 weeks (n = 10).

Disclosures: This study received no specific funding from any sources. The authors declared no conflicts of interest.

Source: Sánchez-García V et al. Evaluation of dupilumab dosing regimen in patients with persistently controlled atopic dermatitis. J Eur Acad Dermatol Venereol. 2023 (Jul 17). doi: 10.1111/jdv.19348

Key clinical point: Dupilumab + low-potency topical corticosteroids (TCS) led to rapid and sustained improvement in disease severity in all anatomical regions (head and neck, trunk, upper extremities, and lower extremities) in children with moderate-to-severe atopic dermatitis (AD).

Major finding: The dupilumab + TCS vs placebo + TCS group had a significant improvement in least-squares mean Eczema Area and Severity Index scores in all 4 anatomical regions by week 2 (all P < .0001) that sustained throughout the 16-week treatment.

Study details: This post hoc analysis of the LIBERTY AD PRESCHOOL trial included 162 children (age, 6 months-5 years) with moderate-to-severe AD who were randomly assigned to receive dupilumab + low-potency TCS or placebo + low-potency TCS every 4 weeks.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Five authors declared being employees or stockholders of Sanofi/Regeneron. The rest declared serving as consultants, investigators, speakers, or advisory board members for and receiving grants or personal fees from various sources, including Sanofi and Regeneron.

Source: Siegfried EC et al. Dupilumab treatment leads to rapid and consistent improvement of atopic dermatitis in all anatomical regions in patients aged 6 months to 5 years. Dermatol Ther (Heidelb). 2023 (Jul 22). doi: 10.1007/s13555-023-00960-w

Key clinical point: Dupilumab + low-potency topical corticosteroids (TCS) led to rapid and sustained improvement in disease severity in all anatomical regions (head and neck, trunk, upper extremities, and lower extremities) in children with moderate-to-severe atopic dermatitis (AD).

Major finding: The dupilumab + TCS vs placebo + TCS group had a significant improvement in least-squares mean Eczema Area and Severity Index scores in all 4 anatomical regions by week 2 (all P < .0001) that sustained throughout the 16-week treatment.

Study details: This post hoc analysis of the LIBERTY AD PRESCHOOL trial included 162 children (age, 6 months-5 years) with moderate-to-severe AD who were randomly assigned to receive dupilumab + low-potency TCS or placebo + low-potency TCS every 4 weeks.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Five authors declared being employees or stockholders of Sanofi/Regeneron. The rest declared serving as consultants, investigators, speakers, or advisory board members for and receiving grants or personal fees from various sources, including Sanofi and Regeneron.

Source: Siegfried EC et al. Dupilumab treatment leads to rapid and consistent improvement of atopic dermatitis in all anatomical regions in patients aged 6 months to 5 years. Dermatol Ther (Heidelb). 2023 (Jul 22). doi: 10.1007/s13555-023-00960-w

Key clinical point: Dupilumab + low-potency topical corticosteroids (TCS) led to rapid and sustained improvement in disease severity in all anatomical regions (head and neck, trunk, upper extremities, and lower extremities) in children with moderate-to-severe atopic dermatitis (AD).

Major finding: The dupilumab + TCS vs placebo + TCS group had a significant improvement in least-squares mean Eczema Area and Severity Index scores in all 4 anatomical regions by week 2 (all P < .0001) that sustained throughout the 16-week treatment.

Study details: This post hoc analysis of the LIBERTY AD PRESCHOOL trial included 162 children (age, 6 months-5 years) with moderate-to-severe AD who were randomly assigned to receive dupilumab + low-potency TCS or placebo + low-potency TCS every 4 weeks.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Five authors declared being employees or stockholders of Sanofi/Regeneron. The rest declared serving as consultants, investigators, speakers, or advisory board members for and receiving grants or personal fees from various sources, including Sanofi and Regeneron.

Source: Siegfried EC et al. Dupilumab treatment leads to rapid and consistent improvement of atopic dermatitis in all anatomical regions in patients aged 6 months to 5 years. Dermatol Ther (Heidelb). 2023 (Jul 22). doi: 10.1007/s13555-023-00960-w

Key clinical point: Emollient bathing at 2 months is significantly associated with the development of atopic dermatitis (AD) by 2 years of age.

Major finding: The odds of developing AD were significantly higher among infants who had emollient baths and frequent (> 1 time weekly) emollient application at 2 months of age compared with infants who had neither at 6 months (adjusted odds ratio [aOR] 1.74; P =  .038), 12 months (aOR 2.59; P < .001), and 24 months (aOR 1.87; P = .009) of age.

Study details: Findings are from a secondary analysis of the observational Cork BASELINE Birth Cohort Study and included 1505 healthy firstborn term infants who did or did not receive emollient baths and did or did not have emollients applied frequently at 2 months of age.

Disclosures: This study was supported by the Science Foundation Ireland and Johnson & Johnson Santé Beauté France. J O’B Hourihane declared receiving research funding, speaker fees, and consulting fees from various sources.

Source: O'Connor C et al. Early emollient bathing is associated with subsequent atopic dermatitis in an unselected birth cohort study. Pediatr Allergy Immunol. 2023;34(7):e13998 (Jul 18). doi: 10.1111/pai.13998

Key clinical point: Emollient bathing at 2 months is significantly associated with the development of atopic dermatitis (AD) by 2 years of age.

Major finding: The odds of developing AD were significantly higher among infants who had emollient baths and frequent (> 1 time weekly) emollient application at 2 months of age compared with infants who had neither at 6 months (adjusted odds ratio [aOR] 1.74; P =  .038), 12 months (aOR 2.59; P < .001), and 24 months (aOR 1.87; P = .009) of age.

Study details: Findings are from a secondary analysis of the observational Cork BASELINE Birth Cohort Study and included 1505 healthy firstborn term infants who did or did not receive emollient baths and did or did not have emollients applied frequently at 2 months of age.

Disclosures: This study was supported by the Science Foundation Ireland and Johnson & Johnson Santé Beauté France. J O’B Hourihane declared receiving research funding, speaker fees, and consulting fees from various sources.

Source: O'Connor C et al. Early emollient bathing is associated with subsequent atopic dermatitis in an unselected birth cohort study. Pediatr Allergy Immunol. 2023;34(7):e13998 (Jul 18). doi: 10.1111/pai.13998

Key clinical point: Emollient bathing at 2 months is significantly associated with the development of atopic dermatitis (AD) by 2 years of age.

Major finding: The odds of developing AD were significantly higher among infants who had emollient baths and frequent (> 1 time weekly) emollient application at 2 months of age compared with infants who had neither at 6 months (adjusted odds ratio [aOR] 1.74; P =  .038), 12 months (aOR 2.59; P < .001), and 24 months (aOR 1.87; P = .009) of age.

Study details: Findings are from a secondary analysis of the observational Cork BASELINE Birth Cohort Study and included 1505 healthy firstborn term infants who did or did not receive emollient baths and did or did not have emollients applied frequently at 2 months of age.

Disclosures: This study was supported by the Science Foundation Ireland and Johnson & Johnson Santé Beauté France. J O’B Hourihane declared receiving research funding, speaker fees, and consulting fees from various sources.

Source: O'Connor C et al. Early emollient bathing is associated with subsequent atopic dermatitis in an unselected birth cohort study. Pediatr Allergy Immunol. 2023;34(7):e13998 (Jul 18). doi: 10.1111/pai.13998

Key clinical point: The likelihood of using cannabis was significantly higher, whereas that of using e-cigarettes and regular cigarettes was significantly lower, in patients with atopic dermatitis (AD).

Major finding: Patients with AD vs control individuals without AD were significantly more likely to use cannabis (adjusted odds ratio [aOR] 1.49; P < .01) but less likely to use e-cigarettes (aOR 0.71; P < .01) and regular cigarettes (aOR 0.65; P < .01). No significant association was observed between AD and hallucinogen (P = .60), opioid (P = .07), and stimulant (P = .20) use.

Study details: This nested case-control study included 13,756 patients with AD and 55,024 age-, race/ethnicity-, and sex-matched control individuals without AD.

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

Source: Joshi TP et al. Association of atopic dermatitis with substance use disorders: A case-control study in the All of Us Research Program. J Am Acad Dermatol. 2023 (Jul 13). doi: 10.1016/j.jaad.2023.06.051

Key clinical point: The likelihood of using cannabis was significantly higher, whereas that of using e-cigarettes and regular cigarettes was significantly lower, in patients with atopic dermatitis (AD).

Major finding: Patients with AD vs control individuals without AD were significantly more likely to use cannabis (adjusted odds ratio [aOR] 1.49; P < .01) but less likely to use e-cigarettes (aOR 0.71; P < .01) and regular cigarettes (aOR 0.65; P < .01). No significant association was observed between AD and hallucinogen (P = .60), opioid (P = .07), and stimulant (P = .20) use.

Study details: This nested case-control study included 13,756 patients with AD and 55,024 age-, race/ethnicity-, and sex-matched control individuals without AD.

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

Source: Joshi TP et al. Association of atopic dermatitis with substance use disorders: A case-control study in the All of Us Research Program. J Am Acad Dermatol. 2023 (Jul 13). doi: 10.1016/j.jaad.2023.06.051

Key clinical point: The likelihood of using cannabis was significantly higher, whereas that of using e-cigarettes and regular cigarettes was significantly lower, in patients with atopic dermatitis (AD).

Major finding: Patients with AD vs control individuals without AD were significantly more likely to use cannabis (adjusted odds ratio [aOR] 1.49; P < .01) but less likely to use e-cigarettes (aOR 0.71; P < .01) and regular cigarettes (aOR 0.65; P < .01). No significant association was observed between AD and hallucinogen (P = .60), opioid (P = .07), and stimulant (P = .20) use.

Study details: This nested case-control study included 13,756 patients with AD and 55,024 age-, race/ethnicity-, and sex-matched control individuals without AD.

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

Source: Joshi TP et al. Association of atopic dermatitis with substance use disorders: A case-control study in the All of Us Research Program. J Am Acad Dermatol. 2023 (Jul 13). doi: 10.1016/j.jaad.2023.06.051