Atopic Dermatitis

According to the best available evidence, patients with atopic dermatitis (AD) do not appear to face an increased risk of acquiring COVID-19 or becoming hospitalized because of the virus.

“This is an area that will continue to evolve, and further understanding will improve the health care advice that we provide to our patients,” Jacob P. Thyssen, MD, PhD, DmSci, said at the Revolutionizing Atopic Dermatitis virtual symposium. “The general recommendation for now is to continue systemic AD treatments during the pandemic, but the risk of acquiring COVID-19 is different for different drugs.”

According to Thyssen, professor of dermatology at the University of Copenhagen, early management guidance from the European Task Force on Atopic Dermatitis (ETFAD), the European Academy of Allergy and Clinical Immunology (EAACI), and the International Eczema Council (IEC) state that patients with AD who are on biologics or immunosuppressants should continue treatment if they are not infected with COVID-19. For example, the EIC statement says that the IEC “does not recommend temporary interruption of systemic AD treatments affecting the immune system in patients without COVID-19 infection or in those who have COVID-19 but are asymptomatic or have only mild symptoms.”

Guidelines from the EAACI recommend that patients with AD who become infected with COVID-19 withhold biologic treatment for a minimum of 2 weeks until they have recovered and/or have a negative SARS-CoV-2 test.

“However, if you have more severe respiratory disease, the advice to dermatologists is to consult with an infectious medicine specialist or a pulmonologist,” Dr. Thyssen said. “That’s out of our specialty realm. But in terms of AD, there’s no reason to stop treatment as long as the patient has mild symptoms or is asymptomatic. AD patients treated with immunosuppressive agents may have a higher risk of COVID-19 complications. Treatment with traditional immunosuppressant medications does increase the risk of infections. But what about COVID-19?”

Traditional systemic immunosuppressive therapies in AD with azathioprine, cyclosporine, and methotrexate suppress the immune system for 1-3 months, Dr. Thyssen continued. “We do know that vaccination response is reduced when using these agents,” he said. “The half-life of dupilumab [Dupixent] is 12-21 days. It takes about 13 weeks before dupilumab is completely out of the system, but it’s such a targeted therapy that it doesn’t lead to any broad immunosuppression.”

Meanwhile, the half-life of JAK inhibitors such as baricitinib (Olumiant) is about 13 hours. “It’s a broader immune suppressant because there will be off-target effects if you have a high dose, but it’s much more specific than the traditional immunosuppressants,” he said. “We now have JAK1 and JAK2 inhibitors in AD, which do not interfere with vaccine responses to the same degree as traditional immunosuppressants.”

To evaluate the risk for COVID-19 in patients with AD, researchers from the Center for Dermatology Research at the University of Manchester, United Kingdom, performed a cross-sectional study of 13,162 dermatology patients seen in the U.K. between June 2018 and Feb. 2021. Of the 13,162 patients, 624 (4.7%) had AD. They found that 4.8% of patients without a history of COVID-19 infection had AD, compared with 3.4% with a history of COVID-19. The risk for COVID-19 in patients with AD was similar to that of controls (adjusted odds ratio, 0.67).

Authors of a separate cross-sectional study published in May evaluated the health insurance medical records of 269,299 patients who were tested for SARS-CoV-2 across University of California Medical Centers. Of these, 3.6% had a positive test for SARS-CoV-2. Of 5,387 patients with AD, the infection rate was 2.9%, which was lower than in those without AD (3.7%; P = .0063). Hospitalization and mortality were not increased in patients with AD.

Another study, a case-control of more than 4.6 million HMO patients in Israel, found that the intake of systemic corticosteroids, older age, comorbid cardiovascular diseases, metabolic syndrome, and COPD were independent predictors of COVID-19–associated hospitalization. Mortality as a result of COVID-19 was independently predicted by metabolic syndrome and COPD but not by any AD-related variables.

“So, for our AD patients out there, there is no need to fear that they develop a COVID-19 infection or have a severe course, but we do have a few medications that would slightly increase the risk,” Dr. Thyssen said.

In another analysis, researchers evaluated Symphony Health–derived data from the COVID-19 Research Database to evaluate the risk for COVID-19 infection in adults with AD. The AD cohort included 39,417 patients, and the cohort without AD included 397,293 patients. Among AD patients, 8,180 were prescribed prednisone, 2,793 were prescribed dupilumab, 714 were prescribed methotrexate, and 512 were prescribed cyclosporine. The risk for COVID-19 was slightly increased in the AD cohort compared with the non-AD cohort (adjusted incidence rate ratio [IRR], 1.18; P < .0001).

“There can be various explanations for this,” Dr. Thyssen said. “I still think we should maintain that AD itself is not a risk factor for COVID-19, but some of the medications may slightly increase the risk.”

In other findings, the investigators observed that treatment with dupilumab versus no systemic medication decreased the risk for COVID-19 by 34% (adjusted IRR, 0.66; P < .0001), as did methotrexate by 18% (adjusted IRR 0.82; P = .32). However, compared with no systemic medication, the use of prednisone slightly increased the risk of COVID-19 (adjusted IRR, 1.13; P = .03), as did the use of cyclosporine (adjusted IRR, 1.20; P = .32) and azathioprine (adjusted IRR, 1.61; P = .16).

More recently, researchers evaluated the records of 1,237 patients with moderate-to-severe AD (aged 9-95 years) to assess the self-reported severity of COVID-19 symptoms among those who received dupilumab versus other treatments.

Of the 1,237 patients with AD, 632 were on dupilumab, 107 were on other systemic treatments, and 498 were on limited or no treatment. Patients treated with dupilumab were less likely to report moderate-to-severe COVID-19 symptoms compared with patients who were on other systemic treatments, or limited/no treatments.
 

Vaccines and AD

Dr. Thyssen pointed out that the risk-benefit ratio of currently approved COVID-19 vaccines is better than the risk for an infection with SARS-CoV-2. “AD is not a contraindication to vaccination,” he said. “COVID-19 vaccine does not cause AD worsening since the vaccination response is mainly Th1 skewed.” He added that systemic immunosuppressants and JAK inhibitors used to treat AD may attenuate the vaccination response, but no attenuation is expected with dupilumab. “The half-life of JAK inhibitors is so short that vaccination followed by 1 week of pause treatment is a good strategy for patients.”

Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Asian, Arena, Almirall, AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.

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

According to the best available evidence, patients with atopic dermatitis (AD) do not appear to face an increased risk of acquiring COVID-19 or becoming hospitalized because of the virus.

“This is an area that will continue to evolve, and further understanding will improve the health care advice that we provide to our patients,” Jacob P. Thyssen, MD, PhD, DmSci, said at the Revolutionizing Atopic Dermatitis virtual symposium. “The general recommendation for now is to continue systemic AD treatments during the pandemic, but the risk of acquiring COVID-19 is different for different drugs.”

According to Thyssen, professor of dermatology at the University of Copenhagen, early management guidance from the European Task Force on Atopic Dermatitis (ETFAD), the European Academy of Allergy and Clinical Immunology (EAACI), and the International Eczema Council (IEC) state that patients with AD who are on biologics or immunosuppressants should continue treatment if they are not infected with COVID-19. For example, the EIC statement says that the IEC “does not recommend temporary interruption of systemic AD treatments affecting the immune system in patients without COVID-19 infection or in those who have COVID-19 but are asymptomatic or have only mild symptoms.”

Guidelines from the EAACI recommend that patients with AD who become infected with COVID-19 withhold biologic treatment for a minimum of 2 weeks until they have recovered and/or have a negative SARS-CoV-2 test.

“However, if you have more severe respiratory disease, the advice to dermatologists is to consult with an infectious medicine specialist or a pulmonologist,” Dr. Thyssen said. “That’s out of our specialty realm. But in terms of AD, there’s no reason to stop treatment as long as the patient has mild symptoms or is asymptomatic. AD patients treated with immunosuppressive agents may have a higher risk of COVID-19 complications. Treatment with traditional immunosuppressant medications does increase the risk of infections. But what about COVID-19?”

Traditional systemic immunosuppressive therapies in AD with azathioprine, cyclosporine, and methotrexate suppress the immune system for 1-3 months, Dr. Thyssen continued. “We do know that vaccination response is reduced when using these agents,” he said. “The half-life of dupilumab [Dupixent] is 12-21 days. It takes about 13 weeks before dupilumab is completely out of the system, but it’s such a targeted therapy that it doesn’t lead to any broad immunosuppression.”

Meanwhile, the half-life of JAK inhibitors such as baricitinib (Olumiant) is about 13 hours. “It’s a broader immune suppressant because there will be off-target effects if you have a high dose, but it’s much more specific than the traditional immunosuppressants,” he said. “We now have JAK1 and JAK2 inhibitors in AD, which do not interfere with vaccine responses to the same degree as traditional immunosuppressants.”

To evaluate the risk for COVID-19 in patients with AD, researchers from the Center for Dermatology Research at the University of Manchester, United Kingdom, performed a cross-sectional study of 13,162 dermatology patients seen in the U.K. between June 2018 and Feb. 2021. Of the 13,162 patients, 624 (4.7%) had AD. They found that 4.8% of patients without a history of COVID-19 infection had AD, compared with 3.4% with a history of COVID-19. The risk for COVID-19 in patients with AD was similar to that of controls (adjusted odds ratio, 0.67).

Authors of a separate cross-sectional study published in May evaluated the health insurance medical records of 269,299 patients who were tested for SARS-CoV-2 across University of California Medical Centers. Of these, 3.6% had a positive test for SARS-CoV-2. Of 5,387 patients with AD, the infection rate was 2.9%, which was lower than in those without AD (3.7%; P = .0063). Hospitalization and mortality were not increased in patients with AD.

Another study, a case-control of more than 4.6 million HMO patients in Israel, found that the intake of systemic corticosteroids, older age, comorbid cardiovascular diseases, metabolic syndrome, and COPD were independent predictors of COVID-19–associated hospitalization. Mortality as a result of COVID-19 was independently predicted by metabolic syndrome and COPD but not by any AD-related variables.

“So, for our AD patients out there, there is no need to fear that they develop a COVID-19 infection or have a severe course, but we do have a few medications that would slightly increase the risk,” Dr. Thyssen said.

In another analysis, researchers evaluated Symphony Health–derived data from the COVID-19 Research Database to evaluate the risk for COVID-19 infection in adults with AD. The AD cohort included 39,417 patients, and the cohort without AD included 397,293 patients. Among AD patients, 8,180 were prescribed prednisone, 2,793 were prescribed dupilumab, 714 were prescribed methotrexate, and 512 were prescribed cyclosporine. The risk for COVID-19 was slightly increased in the AD cohort compared with the non-AD cohort (adjusted incidence rate ratio [IRR], 1.18; P < .0001).

“There can be various explanations for this,” Dr. Thyssen said. “I still think we should maintain that AD itself is not a risk factor for COVID-19, but some of the medications may slightly increase the risk.”

In other findings, the investigators observed that treatment with dupilumab versus no systemic medication decreased the risk for COVID-19 by 34% (adjusted IRR, 0.66; P < .0001), as did methotrexate by 18% (adjusted IRR 0.82; P = .32). However, compared with no systemic medication, the use of prednisone slightly increased the risk of COVID-19 (adjusted IRR, 1.13; P = .03), as did the use of cyclosporine (adjusted IRR, 1.20; P = .32) and azathioprine (adjusted IRR, 1.61; P = .16).

More recently, researchers evaluated the records of 1,237 patients with moderate-to-severe AD (aged 9-95 years) to assess the self-reported severity of COVID-19 symptoms among those who received dupilumab versus other treatments.

Of the 1,237 patients with AD, 632 were on dupilumab, 107 were on other systemic treatments, and 498 were on limited or no treatment. Patients treated with dupilumab were less likely to report moderate-to-severe COVID-19 symptoms compared with patients who were on other systemic treatments, or limited/no treatments.
 

Vaccines and AD

Dr. Thyssen pointed out that the risk-benefit ratio of currently approved COVID-19 vaccines is better than the risk for an infection with SARS-CoV-2. “AD is not a contraindication to vaccination,” he said. “COVID-19 vaccine does not cause AD worsening since the vaccination response is mainly Th1 skewed.” He added that systemic immunosuppressants and JAK inhibitors used to treat AD may attenuate the vaccination response, but no attenuation is expected with dupilumab. “The half-life of JAK inhibitors is so short that vaccination followed by 1 week of pause treatment is a good strategy for patients.”

Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Asian, Arena, Almirall, AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.

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

According to the best available evidence, patients with atopic dermatitis (AD) do not appear to face an increased risk of acquiring COVID-19 or becoming hospitalized because of the virus.

“This is an area that will continue to evolve, and further understanding will improve the health care advice that we provide to our patients,” Jacob P. Thyssen, MD, PhD, DmSci, said at the Revolutionizing Atopic Dermatitis virtual symposium. “The general recommendation for now is to continue systemic AD treatments during the pandemic, but the risk of acquiring COVID-19 is different for different drugs.”

According to Thyssen, professor of dermatology at the University of Copenhagen, early management guidance from the European Task Force on Atopic Dermatitis (ETFAD), the European Academy of Allergy and Clinical Immunology (EAACI), and the International Eczema Council (IEC) state that patients with AD who are on biologics or immunosuppressants should continue treatment if they are not infected with COVID-19. For example, the EIC statement says that the IEC “does not recommend temporary interruption of systemic AD treatments affecting the immune system in patients without COVID-19 infection or in those who have COVID-19 but are asymptomatic or have only mild symptoms.”

Guidelines from the EAACI recommend that patients with AD who become infected with COVID-19 withhold biologic treatment for a minimum of 2 weeks until they have recovered and/or have a negative SARS-CoV-2 test.

“However, if you have more severe respiratory disease, the advice to dermatologists is to consult with an infectious medicine specialist or a pulmonologist,” Dr. Thyssen said. “That’s out of our specialty realm. But in terms of AD, there’s no reason to stop treatment as long as the patient has mild symptoms or is asymptomatic. AD patients treated with immunosuppressive agents may have a higher risk of COVID-19 complications. Treatment with traditional immunosuppressant medications does increase the risk of infections. But what about COVID-19?”

Traditional systemic immunosuppressive therapies in AD with azathioprine, cyclosporine, and methotrexate suppress the immune system for 1-3 months, Dr. Thyssen continued. “We do know that vaccination response is reduced when using these agents,” he said. “The half-life of dupilumab [Dupixent] is 12-21 days. It takes about 13 weeks before dupilumab is completely out of the system, but it’s such a targeted therapy that it doesn’t lead to any broad immunosuppression.”

Meanwhile, the half-life of JAK inhibitors such as baricitinib (Olumiant) is about 13 hours. “It’s a broader immune suppressant because there will be off-target effects if you have a high dose, but it’s much more specific than the traditional immunosuppressants,” he said. “We now have JAK1 and JAK2 inhibitors in AD, which do not interfere with vaccine responses to the same degree as traditional immunosuppressants.”

To evaluate the risk for COVID-19 in patients with AD, researchers from the Center for Dermatology Research at the University of Manchester, United Kingdom, performed a cross-sectional study of 13,162 dermatology patients seen in the U.K. between June 2018 and Feb. 2021. Of the 13,162 patients, 624 (4.7%) had AD. They found that 4.8% of patients without a history of COVID-19 infection had AD, compared with 3.4% with a history of COVID-19. The risk for COVID-19 in patients with AD was similar to that of controls (adjusted odds ratio, 0.67).

Authors of a separate cross-sectional study published in May evaluated the health insurance medical records of 269,299 patients who were tested for SARS-CoV-2 across University of California Medical Centers. Of these, 3.6% had a positive test for SARS-CoV-2. Of 5,387 patients with AD, the infection rate was 2.9%, which was lower than in those without AD (3.7%; P = .0063). Hospitalization and mortality were not increased in patients with AD.

Another study, a case-control of more than 4.6 million HMO patients in Israel, found that the intake of systemic corticosteroids, older age, comorbid cardiovascular diseases, metabolic syndrome, and COPD were independent predictors of COVID-19–associated hospitalization. Mortality as a result of COVID-19 was independently predicted by metabolic syndrome and COPD but not by any AD-related variables.

“So, for our AD patients out there, there is no need to fear that they develop a COVID-19 infection or have a severe course, but we do have a few medications that would slightly increase the risk,” Dr. Thyssen said.

In another analysis, researchers evaluated Symphony Health–derived data from the COVID-19 Research Database to evaluate the risk for COVID-19 infection in adults with AD. The AD cohort included 39,417 patients, and the cohort without AD included 397,293 patients. Among AD patients, 8,180 were prescribed prednisone, 2,793 were prescribed dupilumab, 714 were prescribed methotrexate, and 512 were prescribed cyclosporine. The risk for COVID-19 was slightly increased in the AD cohort compared with the non-AD cohort (adjusted incidence rate ratio [IRR], 1.18; P < .0001).

“There can be various explanations for this,” Dr. Thyssen said. “I still think we should maintain that AD itself is not a risk factor for COVID-19, but some of the medications may slightly increase the risk.”

In other findings, the investigators observed that treatment with dupilumab versus no systemic medication decreased the risk for COVID-19 by 34% (adjusted IRR, 0.66; P < .0001), as did methotrexate by 18% (adjusted IRR 0.82; P = .32). However, compared with no systemic medication, the use of prednisone slightly increased the risk of COVID-19 (adjusted IRR, 1.13; P = .03), as did the use of cyclosporine (adjusted IRR, 1.20; P = .32) and azathioprine (adjusted IRR, 1.61; P = .16).

More recently, researchers evaluated the records of 1,237 patients with moderate-to-severe AD (aged 9-95 years) to assess the self-reported severity of COVID-19 symptoms among those who received dupilumab versus other treatments.

Of the 1,237 patients with AD, 632 were on dupilumab, 107 were on other systemic treatments, and 498 were on limited or no treatment. Patients treated with dupilumab were less likely to report moderate-to-severe COVID-19 symptoms compared with patients who were on other systemic treatments, or limited/no treatments.
 

Vaccines and AD

Dr. Thyssen pointed out that the risk-benefit ratio of currently approved COVID-19 vaccines is better than the risk for an infection with SARS-CoV-2. “AD is not a contraindication to vaccination,” he said. “COVID-19 vaccine does not cause AD worsening since the vaccination response is mainly Th1 skewed.” He added that systemic immunosuppressants and JAK inhibitors used to treat AD may attenuate the vaccination response, but no attenuation is expected with dupilumab. “The half-life of JAK inhibitors is so short that vaccination followed by 1 week of pause treatment is a good strategy for patients.”

Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Asian, Arena, Almirall, AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.

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

Key clinical point: Combination of dupilumab and topical corticosteroids (TCS) improved signs of atopic dermatitis (AD) rapidly and consistently across all anatomic regions in adults with moderate-to-severe AD.

Major finding: Dupilumab+TCS vs. placebo+TCS significantly improved infiltration/papulation score in head and neck, trunk, and upper extremities; excoriation score in trunk, upper, and lower extremities; lichenification score in trunk by week 2; and erythema score in head and neck and trunk by week 4 (all P ≤ .001), with all improvements sustained until week 52 (P ≤ .001).

Study details: Findings are post hoc analysis of 52-week phase 3 LIBERTY AD CHRONOS trial including 421 patients with moderate-to-severe AD who were randomly assigned to receive dupilumab+TCS or placebo+TCS.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. Some of the authors declared receiving grants and personal fees or serving as a consultant, speaker, advisory board member, and investigator for various sources. Some of the authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi Genzyme.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 (Nov 22). Doi: 10.1007/s13555-021-00638-1.

Key clinical point: Combination of dupilumab and topical corticosteroids (TCS) improved signs of atopic dermatitis (AD) rapidly and consistently across all anatomic regions in adults with moderate-to-severe AD.

Major finding: Dupilumab+TCS vs. placebo+TCS significantly improved infiltration/papulation score in head and neck, trunk, and upper extremities; excoriation score in trunk, upper, and lower extremities; lichenification score in trunk by week 2; and erythema score in head and neck and trunk by week 4 (all P ≤ .001), with all improvements sustained until week 52 (P ≤ .001).

Study details: Findings are post hoc analysis of 52-week phase 3 LIBERTY AD CHRONOS trial including 421 patients with moderate-to-severe AD who were randomly assigned to receive dupilumab+TCS or placebo+TCS.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. Some of the authors declared receiving grants and personal fees or serving as a consultant, speaker, advisory board member, and investigator for various sources. Some of the authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi Genzyme.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 (Nov 22). Doi: 10.1007/s13555-021-00638-1.

Key clinical point: Combination of dupilumab and topical corticosteroids (TCS) improved signs of atopic dermatitis (AD) rapidly and consistently across all anatomic regions in adults with moderate-to-severe AD.

Major finding: Dupilumab+TCS vs. placebo+TCS significantly improved infiltration/papulation score in head and neck, trunk, and upper extremities; excoriation score in trunk, upper, and lower extremities; lichenification score in trunk by week 2; and erythema score in head and neck and trunk by week 4 (all P ≤ .001), with all improvements sustained until week 52 (P ≤ .001).

Study details: Findings are post hoc analysis of 52-week phase 3 LIBERTY AD CHRONOS trial including 421 patients with moderate-to-severe AD who were randomly assigned to receive dupilumab+TCS or placebo+TCS.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. Some of the authors declared receiving grants and personal fees or serving as a consultant, speaker, advisory board member, and investigator for various sources. Some of the authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi Genzyme.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 (Nov 22). Doi: 10.1007/s13555-021-00638-1.

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) are most likely to benefit from long-term 2 mg baricitinib therapy if affected body surface area (BSA) at baseline was 10%-50% and early clinical improvement in itch/skin inflammation was seen after 4-8 weeks of treatment initiation.

Major finding: At week 16, at least 75% improvement in Eczema Area and Severity Index (EASI75) was achieved by a higher proportion of patients treated with 2 mg baricitinib with baseline BSA 10%-50% vs. >50% (37.5% vs. 9.5%) and those with vs. without an early response to 2 mg baricitinib at week 4 (55.4% vs. 16.7%) and week 8 (66.7% vs. 2.1%).

Study details: Findings are post hoc analysis of the ongoing phase 3 BREEZE-AD5 trial including 440 adults with moderate-to-severe AD who were randomly assigned to receive once-daily 1 mg baricitinib, 2 mg baricitinib, or placebo.

Disclosures: This work was funded by Eli Lilly and Company. The authors declared having ties with several sources including Eli Lilly. Four authors declared being current or former employees and shareholders of Eli Lilly.

Source: Silverberg JI et al. Dermatol Ther (Heidelb). 2021 (Nov 30). Doi: 10.1007/s13555-021-00640-7.

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) are most likely to benefit from long-term 2 mg baricitinib therapy if affected body surface area (BSA) at baseline was 10%-50% and early clinical improvement in itch/skin inflammation was seen after 4-8 weeks of treatment initiation.

Major finding: At week 16, at least 75% improvement in Eczema Area and Severity Index (EASI75) was achieved by a higher proportion of patients treated with 2 mg baricitinib with baseline BSA 10%-50% vs. >50% (37.5% vs. 9.5%) and those with vs. without an early response to 2 mg baricitinib at week 4 (55.4% vs. 16.7%) and week 8 (66.7% vs. 2.1%).

Study details: Findings are post hoc analysis of the ongoing phase 3 BREEZE-AD5 trial including 440 adults with moderate-to-severe AD who were randomly assigned to receive once-daily 1 mg baricitinib, 2 mg baricitinib, or placebo.

Disclosures: This work was funded by Eli Lilly and Company. The authors declared having ties with several sources including Eli Lilly. Four authors declared being current or former employees and shareholders of Eli Lilly.

Source: Silverberg JI et al. Dermatol Ther (Heidelb). 2021 (Nov 30). Doi: 10.1007/s13555-021-00640-7.

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) are most likely to benefit from long-term 2 mg baricitinib therapy if affected body surface area (BSA) at baseline was 10%-50% and early clinical improvement in itch/skin inflammation was seen after 4-8 weeks of treatment initiation.

Major finding: At week 16, at least 75% improvement in Eczema Area and Severity Index (EASI75) was achieved by a higher proportion of patients treated with 2 mg baricitinib with baseline BSA 10%-50% vs. >50% (37.5% vs. 9.5%) and those with vs. without an early response to 2 mg baricitinib at week 4 (55.4% vs. 16.7%) and week 8 (66.7% vs. 2.1%).

Study details: Findings are post hoc analysis of the ongoing phase 3 BREEZE-AD5 trial including 440 adults with moderate-to-severe AD who were randomly assigned to receive once-daily 1 mg baricitinib, 2 mg baricitinib, or placebo.

Disclosures: This work was funded by Eli Lilly and Company. The authors declared having ties with several sources including Eli Lilly. Four authors declared being current or former employees and shareholders of Eli Lilly.

Source: Silverberg JI et al. Dermatol Ther (Heidelb). 2021 (Nov 30). Doi: 10.1007/s13555-021-00640-7.

Key clinical point: Topical tacrolimus (TAC; 0.3% and 0.1%) and topical corticosteroids (TCS) of mild and moderate potency were safe and showed a comparable safety profile in young children with moderate-to-severe atopic dermatitis (AD).

Major finding: Skin-related infections (P = .198), other infections (P = .498), height (P = .601), weight (P = .812), vaccination responses (P = .620), and serum cortisone levels (P = .228) were not significantly different between TAC and TCS groups. In both groups, Eczema Area and Severity Index decreased significantly (P < .0001) and was similar after 36 months (P = .187).

Study details: Findings are from a 36-month follow-up study including 152 children (age 1-3 years) with moderate-to-severe AD who were randomly assigned to receive TCS creams or TAC ointments (0.03% and 0.1%).

Disclosures: The work was supported by the Pediatric Research Foundation, Helsinki University Hospital, Sigrid Juselius Foundation, and others. The authors declared no conflict of interests.

Source: Salava A et al. Clin Exp Dermatol. 2021 (Nov 19). Doi: 10.1111/ced.15024.

Key clinical point: Topical tacrolimus (TAC; 0.3% and 0.1%) and topical corticosteroids (TCS) of mild and moderate potency were safe and showed a comparable safety profile in young children with moderate-to-severe atopic dermatitis (AD).

Major finding: Skin-related infections (P = .198), other infections (P = .498), height (P = .601), weight (P = .812), vaccination responses (P = .620), and serum cortisone levels (P = .228) were not significantly different between TAC and TCS groups. In both groups, Eczema Area and Severity Index decreased significantly (P < .0001) and was similar after 36 months (P = .187).

Study details: Findings are from a 36-month follow-up study including 152 children (age 1-3 years) with moderate-to-severe AD who were randomly assigned to receive TCS creams or TAC ointments (0.03% and 0.1%).

Disclosures: The work was supported by the Pediatric Research Foundation, Helsinki University Hospital, Sigrid Juselius Foundation, and others. The authors declared no conflict of interests.

Source: Salava A et al. Clin Exp Dermatol. 2021 (Nov 19). Doi: 10.1111/ced.15024.

Key clinical point: Topical tacrolimus (TAC; 0.3% and 0.1%) and topical corticosteroids (TCS) of mild and moderate potency were safe and showed a comparable safety profile in young children with moderate-to-severe atopic dermatitis (AD).

Major finding: Skin-related infections (P = .198), other infections (P = .498), height (P = .601), weight (P = .812), vaccination responses (P = .620), and serum cortisone levels (P = .228) were not significantly different between TAC and TCS groups. In both groups, Eczema Area and Severity Index decreased significantly (P < .0001) and was similar after 36 months (P = .187).

Study details: Findings are from a 36-month follow-up study including 152 children (age 1-3 years) with moderate-to-severe AD who were randomly assigned to receive TCS creams or TAC ointments (0.03% and 0.1%).

Disclosures: The work was supported by the Pediatric Research Foundation, Helsinki University Hospital, Sigrid Juselius Foundation, and others. The authors declared no conflict of interests.

Source: Salava A et al. Clin Exp Dermatol. 2021 (Nov 19). Doi: 10.1111/ced.15024.

Key clinical point: Patients aged 2 years or older with mild-to-moderate atopic dermatitis (AD) showed a better response to 2% crisaborole ointment than other topical calcineurin inhibitors, such as 1% pimecrolimus and 0.03% tacrolimus.

Major finding: By week 6, the odds of achieving Investigator’s Static Global Assessment score of 0/1 was higher for 2% crisaborole vs. 1% pimecrolimus (odds ratio [OR] 2.03; P < .001) and 0.03% tacrolimus (OR, 1.50; P = .012).

Study details: Findings are from an unanchored matching-adjusted indirect comparison of crisaborole 2% with pimecrolimus 1% and tacrolimus (0.03% and 0.1%) in patients aged 2 years or older who had mild-to-moderate AD using individual patient data from 2 phase 3 randomized controlled trials (RCTs) and comparators used in published RCTs.

Disclosures: This study was funded by Pfizer. The authors declared serving as advisor and speaker and/or receiving consulting fees and funding from several sources. Five employees declared being employees and/or shareholders of Pfizer.

Source: Thom H et al. Dermatol Ther (Heidelb). 2021 (Dec 8). Doi: 10.1007/s13555-021-00646-1.

Key clinical point: Patients aged 2 years or older with mild-to-moderate atopic dermatitis (AD) showed a better response to 2% crisaborole ointment than other topical calcineurin inhibitors, such as 1% pimecrolimus and 0.03% tacrolimus.

Major finding: By week 6, the odds of achieving Investigator’s Static Global Assessment score of 0/1 was higher for 2% crisaborole vs. 1% pimecrolimus (odds ratio [OR] 2.03; P < .001) and 0.03% tacrolimus (OR, 1.50; P = .012).

Study details: Findings are from an unanchored matching-adjusted indirect comparison of crisaborole 2% with pimecrolimus 1% and tacrolimus (0.03% and 0.1%) in patients aged 2 years or older who had mild-to-moderate AD using individual patient data from 2 phase 3 randomized controlled trials (RCTs) and comparators used in published RCTs.

Disclosures: This study was funded by Pfizer. The authors declared serving as advisor and speaker and/or receiving consulting fees and funding from several sources. Five employees declared being employees and/or shareholders of Pfizer.

Source: Thom H et al. Dermatol Ther (Heidelb). 2021 (Dec 8). Doi: 10.1007/s13555-021-00646-1.

Key clinical point: Patients aged 2 years or older with mild-to-moderate atopic dermatitis (AD) showed a better response to 2% crisaborole ointment than other topical calcineurin inhibitors, such as 1% pimecrolimus and 0.03% tacrolimus.

Major finding: By week 6, the odds of achieving Investigator’s Static Global Assessment score of 0/1 was higher for 2% crisaborole vs. 1% pimecrolimus (odds ratio [OR] 2.03; P < .001) and 0.03% tacrolimus (OR, 1.50; P = .012).

Study details: Findings are from an unanchored matching-adjusted indirect comparison of crisaborole 2% with pimecrolimus 1% and tacrolimus (0.03% and 0.1%) in patients aged 2 years or older who had mild-to-moderate AD using individual patient data from 2 phase 3 randomized controlled trials (RCTs) and comparators used in published RCTs.

Disclosures: This study was funded by Pfizer. The authors declared serving as advisor and speaker and/or receiving consulting fees and funding from several sources. Five employees declared being employees and/or shareholders of Pfizer.

Source: Thom H et al. Dermatol Ther (Heidelb). 2021 (Dec 8). Doi: 10.1007/s13555-021-00646-1.

Key clinical point: Add-on sublingual immunotherapy (SLIT) with house dust mite (HDM) extract may effectively improve signs and symptoms of atopic dermatitis in patients sensitized to HDM.

Major finding: After 18 months, the SCORing Atopic Dermatitis score decrease in HDM SLIT vs. placebo groups was 55.6% vs. 34.5%, with a significant mean difference of 20.4 (95% credible interval [CI] 3.89-37.3). A significantly higher proportion of patients in the HDM SLIT vs. placebo groups achieved the Investigator’s Global Assessment score of 0/1 (relative risk 2.63; 95% CI, 1.09-6.39). Headache and abdominal pain were the most common adverse events reported by both groups.

Study details: Findings are from a phase 4 study including 91 patients, mostly with moderate-to-severe AD, who were randomly assigned to receive HDM SLIT or placebo for 18 months along with background AD therapy.

Disclosures: This study was funded by the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and others. Two authors declared receiving doctoral scholarship and research grants from various sources.

Source: Langer SS et al. J Allergy Clin Immunol Pract. 2021 (Nov 9). Doi: 10.1016/j.jaip.2021.10.060.

Key clinical point: Add-on sublingual immunotherapy (SLIT) with house dust mite (HDM) extract may effectively improve signs and symptoms of atopic dermatitis in patients sensitized to HDM.

Major finding: After 18 months, the SCORing Atopic Dermatitis score decrease in HDM SLIT vs. placebo groups was 55.6% vs. 34.5%, with a significant mean difference of 20.4 (95% credible interval [CI] 3.89-37.3). A significantly higher proportion of patients in the HDM SLIT vs. placebo groups achieved the Investigator’s Global Assessment score of 0/1 (relative risk 2.63; 95% CI, 1.09-6.39). Headache and abdominal pain were the most common adverse events reported by both groups.

Study details: Findings are from a phase 4 study including 91 patients, mostly with moderate-to-severe AD, who were randomly assigned to receive HDM SLIT or placebo for 18 months along with background AD therapy.

Disclosures: This study was funded by the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and others. Two authors declared receiving doctoral scholarship and research grants from various sources.

Source: Langer SS et al. J Allergy Clin Immunol Pract. 2021 (Nov 9). Doi: 10.1016/j.jaip.2021.10.060.

Key clinical point: Add-on sublingual immunotherapy (SLIT) with house dust mite (HDM) extract may effectively improve signs and symptoms of atopic dermatitis in patients sensitized to HDM.

Major finding: After 18 months, the SCORing Atopic Dermatitis score decrease in HDM SLIT vs. placebo groups was 55.6% vs. 34.5%, with a significant mean difference of 20.4 (95% credible interval [CI] 3.89-37.3). A significantly higher proportion of patients in the HDM SLIT vs. placebo groups achieved the Investigator’s Global Assessment score of 0/1 (relative risk 2.63; 95% CI, 1.09-6.39). Headache and abdominal pain were the most common adverse events reported by both groups.

Study details: Findings are from a phase 4 study including 91 patients, mostly with moderate-to-severe AD, who were randomly assigned to receive HDM SLIT or placebo for 18 months along with background AD therapy.

Disclosures: This study was funded by the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and others. Two authors declared receiving doctoral scholarship and research grants from various sources.

Source: Langer SS et al. J Allergy Clin Immunol Pract. 2021 (Nov 9). Doi: 10.1016/j.jaip.2021.10.060.

Key clinical point: Atopic dermatitis (AD) was associated with an increased burden of a wide range of psychiatric, dermatologic, and extracutaneous comorbidities, increased awareness of which could help better patient management.

Major finding: Compared with control participants, adults with AD were at an increased risk for psychiatric disorders, such as anxiety (odds ratio [OR] 1.44) and obsessive-compulsive disorder (OR 2.01); autoimmune diseases, such as alopecia areata (OR 6.01) and vitiligo (OR 4.44); dermatologic problems, such as cellulitis (OR 2.52); and systemic conditions, such as lymphoid malignancy (OR 1.91), atherosclerosis (OR 1.69), and metabolic syndrome (OR 1.47; all P < .001).

Study details: Findings are a retrospective analysis of 39,779 patients with AD, who were matched with 353,743 control participants from the general population.

Disclosures: The corresponding author Dr. Kwatra received funding from Pfizer and declared serving as an advisory board member, consultant, and investigator for several sources.

Source: Roh YS et al. J Am Acad Dermatol. 2021 (Nov 17). Doi: 10.1016/j.jaad.2021.11.014.

Key clinical point: Atopic dermatitis (AD) was associated with an increased burden of a wide range of psychiatric, dermatologic, and extracutaneous comorbidities, increased awareness of which could help better patient management.

Major finding: Compared with control participants, adults with AD were at an increased risk for psychiatric disorders, such as anxiety (odds ratio [OR] 1.44) and obsessive-compulsive disorder (OR 2.01); autoimmune diseases, such as alopecia areata (OR 6.01) and vitiligo (OR 4.44); dermatologic problems, such as cellulitis (OR 2.52); and systemic conditions, such as lymphoid malignancy (OR 1.91), atherosclerosis (OR 1.69), and metabolic syndrome (OR 1.47; all P < .001).

Study details: Findings are a retrospective analysis of 39,779 patients with AD, who were matched with 353,743 control participants from the general population.

Disclosures: The corresponding author Dr. Kwatra received funding from Pfizer and declared serving as an advisory board member, consultant, and investigator for several sources.

Source: Roh YS et al. J Am Acad Dermatol. 2021 (Nov 17). Doi: 10.1016/j.jaad.2021.11.014.

Key clinical point: Atopic dermatitis (AD) was associated with an increased burden of a wide range of psychiatric, dermatologic, and extracutaneous comorbidities, increased awareness of which could help better patient management.

Major finding: Compared with control participants, adults with AD were at an increased risk for psychiatric disorders, such as anxiety (odds ratio [OR] 1.44) and obsessive-compulsive disorder (OR 2.01); autoimmune diseases, such as alopecia areata (OR 6.01) and vitiligo (OR 4.44); dermatologic problems, such as cellulitis (OR 2.52); and systemic conditions, such as lymphoid malignancy (OR 1.91), atherosclerosis (OR 1.69), and metabolic syndrome (OR 1.47; all P < .001).

Study details: Findings are a retrospective analysis of 39,779 patients with AD, who were matched with 353,743 control participants from the general population.

Disclosures: The corresponding author Dr. Kwatra received funding from Pfizer and declared serving as an advisory board member, consultant, and investigator for several sources.

Source: Roh YS et al. J Am Acad Dermatol. 2021 (Nov 17). Doi: 10.1016/j.jaad.2021.11.014.

Key clinical point: Phototherapy with narrowband (NB) ultraviolet type B (UV-B) light showed high and long-lasting efficacy in atopic dermatitis (AD) with patients with facial involvement and adverse events (AE) responding poorly to the treatment.

Major finding: Overall, 55.4% patients achieved Investigator’s Global Assessment score of 0 and 1 with an overall median response duration of 12 months. Facial involvement (odds ratio [OR] 2.743; P < .001), adverse events (OR 2.366; P = .015), and lower number of treatments (OR 1.017; P = .089) were related with poor response.

Study details: Findings are from a retrospective cohort study of 390 patients with moderate-to-severe AD who were treated with NB-UV-B therapy and followed up for at least 3 years after completing therapy.

Disclosures: This study did not report any funding. The authors declared no conflict of interests.

Source: Ben Mordehai Y et al. Dermatitis. 2021 (Nov 27). Doi: 10.1097/DER.0000000000000810.

Key clinical point: Phototherapy with narrowband (NB) ultraviolet type B (UV-B) light showed high and long-lasting efficacy in atopic dermatitis (AD) with patients with facial involvement and adverse events (AE) responding poorly to the treatment.

Major finding: Overall, 55.4% patients achieved Investigator’s Global Assessment score of 0 and 1 with an overall median response duration of 12 months. Facial involvement (odds ratio [OR] 2.743; P < .001), adverse events (OR 2.366; P = .015), and lower number of treatments (OR 1.017; P = .089) were related with poor response.

Study details: Findings are from a retrospective cohort study of 390 patients with moderate-to-severe AD who were treated with NB-UV-B therapy and followed up for at least 3 years after completing therapy.

Disclosures: This study did not report any funding. The authors declared no conflict of interests.

Source: Ben Mordehai Y et al. Dermatitis. 2021 (Nov 27). Doi: 10.1097/DER.0000000000000810.

Key clinical point: Phototherapy with narrowband (NB) ultraviolet type B (UV-B) light showed high and long-lasting efficacy in atopic dermatitis (AD) with patients with facial involvement and adverse events (AE) responding poorly to the treatment.

Major finding: Overall, 55.4% patients achieved Investigator’s Global Assessment score of 0 and 1 with an overall median response duration of 12 months. Facial involvement (odds ratio [OR] 2.743; P < .001), adverse events (OR 2.366; P = .015), and lower number of treatments (OR 1.017; P = .089) were related with poor response.

Study details: Findings are from a retrospective cohort study of 390 patients with moderate-to-severe AD who were treated with NB-UV-B therapy and followed up for at least 3 years after completing therapy.

Disclosures: This study did not report any funding. The authors declared no conflict of interests.

Source: Ben Mordehai Y et al. Dermatitis. 2021 (Nov 27). Doi: 10.1097/DER.0000000000000810.

Key clinical point: Ocular surface diseases (OSD), particularly conjunctivitis, are prevalent among patients with atopic dermatitis (AD), with the prevalence increasing with AD severity and childhood onset of AD.

Major finding: Of all OSDs, lifetime prevalence was highest for conjunctivitis (66.6%), followed by other OSDs, such as hordeolum (63.5%), blepharitis (11%), and keratitis (9.7%). The lifetime occurrence of conjunctivitis was higher for mild (adjusted odds ratio [aOR] 1.48; 95% CI 1.02-2.14), moderate (aOR 1.73; 95% CI 1.19-2.53), and severe (aOR 2.17; 95% CI 1.42-3.21) AD vs. inactive AD and for childhood-onset vs. adult-onset AD (aOR 1.34; 95% CI 1.16-1.56).

Study details: Findings are from a nationwide, cross-sectional questionnaire-based survey sent to 16,718 patients with AD, of which 7,044 patients responded.

Disclosures: This study was funded by the Kgl. Hofbundtmager Aage Bang Foundation. The authors declared serving as advisory board members, investigators, and consultants or receiving honoraria, grants, and funding from several sources.

Source: Rønnstad ATM et al. J Eur Acad Dermatol Venereol. 2021 (Nov 23). Doi: 10.1111/jdv.17832.

Key clinical point: Ocular surface diseases (OSD), particularly conjunctivitis, are prevalent among patients with atopic dermatitis (AD), with the prevalence increasing with AD severity and childhood onset of AD.

Major finding: Of all OSDs, lifetime prevalence was highest for conjunctivitis (66.6%), followed by other OSDs, such as hordeolum (63.5%), blepharitis (11%), and keratitis (9.7%). The lifetime occurrence of conjunctivitis was higher for mild (adjusted odds ratio [aOR] 1.48; 95% CI 1.02-2.14), moderate (aOR 1.73; 95% CI 1.19-2.53), and severe (aOR 2.17; 95% CI 1.42-3.21) AD vs. inactive AD and for childhood-onset vs. adult-onset AD (aOR 1.34; 95% CI 1.16-1.56).

Study details: Findings are from a nationwide, cross-sectional questionnaire-based survey sent to 16,718 patients with AD, of which 7,044 patients responded.

Disclosures: This study was funded by the Kgl. Hofbundtmager Aage Bang Foundation. The authors declared serving as advisory board members, investigators, and consultants or receiving honoraria, grants, and funding from several sources.

Source: Rønnstad ATM et al. J Eur Acad Dermatol Venereol. 2021 (Nov 23). Doi: 10.1111/jdv.17832.

Key clinical point: Ocular surface diseases (OSD), particularly conjunctivitis, are prevalent among patients with atopic dermatitis (AD), with the prevalence increasing with AD severity and childhood onset of AD.

Major finding: Of all OSDs, lifetime prevalence was highest for conjunctivitis (66.6%), followed by other OSDs, such as hordeolum (63.5%), blepharitis (11%), and keratitis (9.7%). The lifetime occurrence of conjunctivitis was higher for mild (adjusted odds ratio [aOR] 1.48; 95% CI 1.02-2.14), moderate (aOR 1.73; 95% CI 1.19-2.53), and severe (aOR 2.17; 95% CI 1.42-3.21) AD vs. inactive AD and for childhood-onset vs. adult-onset AD (aOR 1.34; 95% CI 1.16-1.56).

Study details: Findings are from a nationwide, cross-sectional questionnaire-based survey sent to 16,718 patients with AD, of which 7,044 patients responded.

Disclosures: This study was funded by the Kgl. Hofbundtmager Aage Bang Foundation. The authors declared serving as advisory board members, investigators, and consultants or receiving honoraria, grants, and funding from several sources.

Source: Rønnstad ATM et al. J Eur Acad Dermatol Venereol. 2021 (Nov 23). Doi: 10.1111/jdv.17832.

Key clinical point: Treatment with once-daily oral abrocitinib led to significantly greater improvements in patient-reported outcomes than placebo in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the patient-oriented eczema measure score improved significantly for 100 mg abrocitinib (least square mean change from baseline [LSM] −9.2) and 200 mg abrocitinib (LSM −12.5) vs. placebo (−5.0; P for both < .0001). A significantly higher proportion of patients receiving abrocitinib, both 200 mg and 100 mg, than placebo reported clinically meaningful improvement in pruritus and symptoms assessment for AD and patient global assessment response (all P < .05).

Study details: Findings are from a phase 3 JADE COMPARE study including 837 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg abrocitinib, 100 mg abrocitinib, dupilumab, or placebo, with background topical therapy.

Disclosures: This study was funded by Pfizer. The authors declared serving as a consultants, speakers, advisors, and investigators or receiving grants from Pfizer and other sources. Six authors declared being employees and shareholders of Pfizer.

Source: Thyssen JP et al. J Eur Acad Dermatol Venereol. 2021 (Nov 15). Doi: 10.1111/jdv.17813.

Key clinical point: Treatment with once-daily oral abrocitinib led to significantly greater improvements in patient-reported outcomes than placebo in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the patient-oriented eczema measure score improved significantly for 100 mg abrocitinib (least square mean change from baseline [LSM] −9.2) and 200 mg abrocitinib (LSM −12.5) vs. placebo (−5.0; P for both < .0001). A significantly higher proportion of patients receiving abrocitinib, both 200 mg and 100 mg, than placebo reported clinically meaningful improvement in pruritus and symptoms assessment for AD and patient global assessment response (all P < .05).

Study details: Findings are from a phase 3 JADE COMPARE study including 837 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg abrocitinib, 100 mg abrocitinib, dupilumab, or placebo, with background topical therapy.

Disclosures: This study was funded by Pfizer. The authors declared serving as a consultants, speakers, advisors, and investigators or receiving grants from Pfizer and other sources. Six authors declared being employees and shareholders of Pfizer.

Source: Thyssen JP et al. J Eur Acad Dermatol Venereol. 2021 (Nov 15). Doi: 10.1111/jdv.17813.

Key clinical point: Treatment with once-daily oral abrocitinib led to significantly greater improvements in patient-reported outcomes than placebo in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the patient-oriented eczema measure score improved significantly for 100 mg abrocitinib (least square mean change from baseline [LSM] −9.2) and 200 mg abrocitinib (LSM −12.5) vs. placebo (−5.0; P for both < .0001). A significantly higher proportion of patients receiving abrocitinib, both 200 mg and 100 mg, than placebo reported clinically meaningful improvement in pruritus and symptoms assessment for AD and patient global assessment response (all P < .05).

Study details: Findings are from a phase 3 JADE COMPARE study including 837 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg abrocitinib, 100 mg abrocitinib, dupilumab, or placebo, with background topical therapy.

Disclosures: This study was funded by Pfizer. The authors declared serving as a consultants, speakers, advisors, and investigators or receiving grants from Pfizer and other sources. Six authors declared being employees and shareholders of Pfizer.

Source: Thyssen JP et al. J Eur Acad Dermatol Venereol. 2021 (Nov 15). Doi: 10.1111/jdv.17813.