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Dr. Feldman scans the journals, so you don’t have to!

Steven R. Feldman, MD, PhD
The idea that changing the gut microbiome affects the skin has always been intriguing to me and, at the same time, seems a lot like pseudoscience. Hoskinson and colleagues report that taking antibiotics in the first year of life disrupts the infant gut microbiome and leads to development of atopic dermatitis (AD). This study followed a previous study by this investigative team in which they found that antibiotics for upper respiratory tract infections led to AD. I'm left wondering whether taking antibiotics leads to gut microbiome changes that cause AD or whether a tendency toward having AD predisposes to infections and antibiotic use that changes the gut microbiome. The latter seems more plausible to me than the former.

Traidl and colleagues report that obesity was linked to worse AD in German patients. The authors hit the nail on the head with their conclusions: "In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance." What might account for the small difference in disease severity? Adherence to treatment is highly variable among patients with AD. A small tendency toward worse adherence in patients with obesity could easily explain the small differences seen in disease severity.

Eichenfeld and colleagues report that topical ruxolitinib maintained good efficacy over a year in open-label use. Topical ruxolitinib is a very effective treatment for AD. If real-life AD patients on topical ruxolitinib were to lose efficacy over time, I'd consider the possibility that they've developed mutant Janus kinase (JAK) enzymes that are no longer responsive to the drug. Just kidding. I doubt that such mutations ever occur. If topical ruxolitinib in AD patients were to lose efficacy over time, I'd strongly consider the possibility that patients' adherence to the treatment is no longer as good as it was before. Long-term adherence to topical treatment can be abysmal. Adherence in clinical trials is probably a lot better than in clinical practice. When we see topical treatments that are effective in clinical trials failing in real-life patients with AD, it may be prudent to address the possibility of poor adherence.

I'd love to see a head-to-head trial of tralokinumab vs dupilumab in the treatment of moderate to severe AD. Lacking that, Torres and colleagues report an indirect comparison of the two drugs in patients also treated with topical steroids. This study, funded by the manufacturer of tralokinumab, reported that the two drugs have similar efficacy. How much of the efficacy was due to the topical steroid use is not clear to me. I'd still love to see a head-to-head trial of tralokinumab vs dupilumab to have a better, more confident sense of their relative efficacy.

Is AD associated with brain cancer, as reported by Xin and colleagues? I'm not an expert in their methodology, but they did find a statistically significant increased risk, with an odds ratio of 1.0005. I understand the odds ratio for smoking and lung cancer to be about 80. Even if the increased odds of 1.005 — no, wait, that's 1.0005 — is truly due to AD, this tiny difference doesn't seem meaningful in any way.

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Professor of Dermatology, Pathology and Social Sciences & Health Policy Wake Forest University School of Medicine, Winston-Salem, NC

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Dr. Feldman scans the journals, so you don’t have to!
Dr. Feldman scans the journals, so you don’t have to!

Steven R. Feldman, MD, PhD
The idea that changing the gut microbiome affects the skin has always been intriguing to me and, at the same time, seems a lot like pseudoscience. Hoskinson and colleagues report that taking antibiotics in the first year of life disrupts the infant gut microbiome and leads to development of atopic dermatitis (AD). This study followed a previous study by this investigative team in which they found that antibiotics for upper respiratory tract infections led to AD. I'm left wondering whether taking antibiotics leads to gut microbiome changes that cause AD or whether a tendency toward having AD predisposes to infections and antibiotic use that changes the gut microbiome. The latter seems more plausible to me than the former.

Traidl and colleagues report that obesity was linked to worse AD in German patients. The authors hit the nail on the head with their conclusions: "In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance." What might account for the small difference in disease severity? Adherence to treatment is highly variable among patients with AD. A small tendency toward worse adherence in patients with obesity could easily explain the small differences seen in disease severity.

Eichenfeld and colleagues report that topical ruxolitinib maintained good efficacy over a year in open-label use. Topical ruxolitinib is a very effective treatment for AD. If real-life AD patients on topical ruxolitinib were to lose efficacy over time, I'd consider the possibility that they've developed mutant Janus kinase (JAK) enzymes that are no longer responsive to the drug. Just kidding. I doubt that such mutations ever occur. If topical ruxolitinib in AD patients were to lose efficacy over time, I'd strongly consider the possibility that patients' adherence to the treatment is no longer as good as it was before. Long-term adherence to topical treatment can be abysmal. Adherence in clinical trials is probably a lot better than in clinical practice. When we see topical treatments that are effective in clinical trials failing in real-life patients with AD, it may be prudent to address the possibility of poor adherence.

I'd love to see a head-to-head trial of tralokinumab vs dupilumab in the treatment of moderate to severe AD. Lacking that, Torres and colleagues report an indirect comparison of the two drugs in patients also treated with topical steroids. This study, funded by the manufacturer of tralokinumab, reported that the two drugs have similar efficacy. How much of the efficacy was due to the topical steroid use is not clear to me. I'd still love to see a head-to-head trial of tralokinumab vs dupilumab to have a better, more confident sense of their relative efficacy.

Is AD associated with brain cancer, as reported by Xin and colleagues? I'm not an expert in their methodology, but they did find a statistically significant increased risk, with an odds ratio of 1.0005. I understand the odds ratio for smoking and lung cancer to be about 80. Even if the increased odds of 1.005 — no, wait, that's 1.0005 — is truly due to AD, this tiny difference doesn't seem meaningful in any way.

Steven R. Feldman, MD, PhD
The idea that changing the gut microbiome affects the skin has always been intriguing to me and, at the same time, seems a lot like pseudoscience. Hoskinson and colleagues report that taking antibiotics in the first year of life disrupts the infant gut microbiome and leads to development of atopic dermatitis (AD). This study followed a previous study by this investigative team in which they found that antibiotics for upper respiratory tract infections led to AD. I'm left wondering whether taking antibiotics leads to gut microbiome changes that cause AD or whether a tendency toward having AD predisposes to infections and antibiotic use that changes the gut microbiome. The latter seems more plausible to me than the former.

Traidl and colleagues report that obesity was linked to worse AD in German patients. The authors hit the nail on the head with their conclusions: "In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance." What might account for the small difference in disease severity? Adherence to treatment is highly variable among patients with AD. A small tendency toward worse adherence in patients with obesity could easily explain the small differences seen in disease severity.

Eichenfeld and colleagues report that topical ruxolitinib maintained good efficacy over a year in open-label use. Topical ruxolitinib is a very effective treatment for AD. If real-life AD patients on topical ruxolitinib were to lose efficacy over time, I'd consider the possibility that they've developed mutant Janus kinase (JAK) enzymes that are no longer responsive to the drug. Just kidding. I doubt that such mutations ever occur. If topical ruxolitinib in AD patients were to lose efficacy over time, I'd strongly consider the possibility that patients' adherence to the treatment is no longer as good as it was before. Long-term adherence to topical treatment can be abysmal. Adherence in clinical trials is probably a lot better than in clinical practice. When we see topical treatments that are effective in clinical trials failing in real-life patients with AD, it may be prudent to address the possibility of poor adherence.

I'd love to see a head-to-head trial of tralokinumab vs dupilumab in the treatment of moderate to severe AD. Lacking that, Torres and colleagues report an indirect comparison of the two drugs in patients also treated with topical steroids. This study, funded by the manufacturer of tralokinumab, reported that the two drugs have similar efficacy. How much of the efficacy was due to the topical steroid use is not clear to me. I'd still love to see a head-to-head trial of tralokinumab vs dupilumab to have a better, more confident sense of their relative efficacy.

Is AD associated with brain cancer, as reported by Xin and colleagues? I'm not an expert in their methodology, but they did find a statistically significant increased risk, with an odds ratio of 1.0005. I understand the odds ratio for smoking and lung cancer to be about 80. Even if the increased odds of 1.005 — no, wait, that's 1.0005 — is truly due to AD, this tiny difference doesn't seem meaningful in any way.

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