Topical Anti‐Inflammatory Treatments for Eczema: A Cochrane Systematic Review and Network Meta‐Analysis
ABSTRACT Objective Eczema is the most burdensome skin condition worldwide and topical anti‐inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti‐inflammatory treatments is uncertain. Design Network meta‐analysis performed withi...
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| Published in | Clinical and experimental allergy Vol. 54; no. 12; pp. 960 - 972 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Wiley Subscription Services, Inc
01.12.2024
John Wiley and Sons Inc |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0954-7894 1365-2222 1365-2222 |
| DOI | 10.1111/cea.14556 |
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| Abstract | ABSTRACT
Objective
Eczema is the most burdensome skin condition worldwide and topical anti‐inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti‐inflammatory treatments is uncertain.
Design
Network meta‐analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti‐inflammatory eczema treatments.
Data Sources
Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023.
Eligibility Criteria for Selected Trials
Included trials were within‐participant or between‐participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti‐inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti‐inflammatory.
Results
We identified 291 trials (45,846 participants), mainly in high‐income countries. Most were industry‐funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta‐analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient‐reported symptoms (40 trials, all low confidence) and clinician‐reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short‐term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer‐term (6–60 months) topical steroids.
Conclusion
Potent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti‐inflammatory treatments for eczema.
Trials of topical anti‐inflammatory eczema treatments are mostly industry‐funded, evaluate short‐term outcomes and carry a high risk of bias due to selective reporting. Data from almost 300 trials suggest that potent steroids, Janus kinase inhibitors and tacrolimus 0.1% are among the most effective topical treatments. Local reactions were most common with tacrolimus 0.1% and crisaborole and least common with steroids. |
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| AbstractList | Eczema is the most burdensome skin condition worldwide and topical anti-inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti-inflammatory treatments is uncertain.OBJECTIVEEczema is the most burdensome skin condition worldwide and topical anti-inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti-inflammatory treatments is uncertain.Network meta-analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti-inflammatory eczema treatments.DESIGNNetwork meta-analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti-inflammatory eczema treatments.Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023.DATA SOURCESCochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023.Included trials were within-participant or between-participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti-inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti-inflammatory.ELIGIBILITY CRITERIA FOR SELECTED TRIALSIncluded trials were within-participant or between-participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti-inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti-inflammatory.We identified 291 trials (45,846 participants), mainly in high-income countries. Most were industry-funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta-analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient-reported symptoms (40 trials, all low confidence) and clinician-reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short-term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer-term (6-60 months) topical steroids.RESULTSWe identified 291 trials (45,846 participants), mainly in high-income countries. Most were industry-funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta-analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient-reported symptoms (40 trials, all low confidence) and clinician-reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short-term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer-term (6-60 months) topical steroids.Potent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti-inflammatory treatments for eczema.CONCLUSIONPotent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti-inflammatory treatments for eczema. Trials of topical anti‐inflammatory eczema treatments are mostly industry‐funded, evaluate short‐term outcomes and carry a high risk of bias due to selective reporting. Data from almost 300 trials suggest that potent steroids, Janus kinase inhibitors and tacrolimus 0.1% are among the most effective topical treatments. Local reactions were most common with tacrolimus 0.1% and crisaborole and least common with steroids. Eczema is the most burdensome skin condition worldwide and topical anti-inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti-inflammatory treatments is uncertain. Network meta-analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti-inflammatory eczema treatments. Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023. Included trials were within-participant or between-participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti-inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti-inflammatory. We identified 291 trials (45,846 participants), mainly in high-income countries. Most were industry-funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta-analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient-reported symptoms (40 trials, all low confidence) and clinician-reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short-term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer-term (6-60 months) topical steroids. Potent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti-inflammatory treatments for eczema. ABSTRACT Objective Eczema is the most burdensome skin condition worldwide and topical anti‐inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti‐inflammatory treatments is uncertain. Design Network meta‐analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti‐inflammatory eczema treatments. Data Sources Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023. Eligibility Criteria for Selected Trials Included trials were within‐participant or between‐participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti‐inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti‐inflammatory. Results We identified 291 trials (45,846 participants), mainly in high‐income countries. Most were industry‐funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta‐analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient‐reported symptoms (40 trials, all low confidence) and clinician‐reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short‐term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer‐term (6–60 months) topical steroids. Conclusion Potent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti‐inflammatory treatments for eczema. Trials of topical anti‐inflammatory eczema treatments are mostly industry‐funded, evaluate short‐term outcomes and carry a high risk of bias due to selective reporting. Data from almost 300 trials suggest that potent steroids, Janus kinase inhibitors and tacrolimus 0.1% are among the most effective topical treatments. Local reactions were most common with tacrolimus 0.1% and crisaborole and least common with steroids. ObjectiveEczema is the most burdensome skin condition worldwide and topical anti‐inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti‐inflammatory treatments is uncertain.DesignNetwork meta‐analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti‐inflammatory eczema treatments.Data SourcesCochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023.Eligibility Criteria for Selected TrialsIncluded trials were within‐participant or between‐participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti‐inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti‐inflammatory.ResultsWe identified 291 trials (45,846 participants), mainly in high‐income countries. Most were industry‐funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta‐analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient‐reported symptoms (40 trials, all low confidence) and clinician‐reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short‐term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer‐term (6–60 months) topical steroids.ConclusionPotent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti‐inflammatory treatments for eczema. |
| Author | Reynolds, Clare Futamura, Masaki Santer, Miriam Axon, Emma Lax, Stephanie J. Candy, Bridget Chu, Derek K. Cro, Suzie Parker, Roses Stuart, Beth Roberts, Amanda Boyle, Robert J. Van Vogt, Eleanor Steele, Lloyd Doyle, Megan Williams, Hywel C. Drucker, Aaron M. |
| AuthorAffiliation | 4 Wellcome Sanger Institute Cambridge UK 5 School of Public Health, Physiotherapy and Sports Science, University College Dublin Dublin Ireland 3 Department of Dermatology Royal Free Hospital London UK 6 Primary Care and Population Sciences, Faculty of Medicine University of Southampton Southampton UK 7 Cochrane MOSS Network, c/o Cochrane Pain Palliative and Supportive Care Group Oxford UK 8 Cochrane Methods Support Unit Cochrane London UK 9 Nottingham Support Group for Carers of Children With Eczema Nottingham UK 14 Department of Medicine, Research and Innovation Institute Women's College Hospital Toronto Ontario Canada 11 Department of Health Research Methods, Evidence & Impact McMaster University Hamilton Ontario Canada 13 Department of Medicine University of Toronto Toronto Ontario Canada 12 Department of Pediatrics National Hospital Organization Nagoya Medical Center Nagoya Japan 2 Imperial Clinical Trials Unit Imperial College London London UK 1 Centre of Evidence Based Dermatology University |
| AuthorAffiliation_xml | – name: 3 Department of Dermatology Royal Free Hospital London UK – name: 15 Section of Inflammation and Repair, National Heart & Lung Institute Imperial College London London UK – name: 9 Nottingham Support Group for Carers of Children With Eczema Nottingham UK – name: 8 Cochrane Methods Support Unit Cochrane London UK – name: 1 Centre of Evidence Based Dermatology University of Nottingham Nottingham UK – name: 13 Department of Medicine University of Toronto Toronto Ontario Canada – name: 5 School of Public Health, Physiotherapy and Sports Science, University College Dublin Dublin Ireland – name: 11 Department of Health Research Methods, Evidence & Impact McMaster University Hamilton Ontario Canada – name: 4 Wellcome Sanger Institute Cambridge UK – name: 12 Department of Pediatrics National Hospital Organization Nagoya Medical Center Nagoya Japan – name: 7 Cochrane MOSS Network, c/o Cochrane Pain Palliative and Supportive Care Group Oxford UK – name: 6 Primary Care and Population Sciences, Faculty of Medicine University of Southampton Southampton UK – name: 14 Department of Medicine, Research and Innovation Institute Women's College Hospital Toronto Ontario Canada – name: 2 Imperial Clinical Trials Unit Imperial College London London UK – name: 10 Department of Medicine McMaster University Hamilton Ontario Canada |
| Author_xml | – sequence: 1 givenname: Stephanie J. orcidid: 0000-0002-7000-9364 surname: Lax fullname: Lax, Stephanie J. organization: University of Nottingham – sequence: 2 givenname: Eleanor surname: Van Vogt fullname: Van Vogt, Eleanor organization: Imperial College London – sequence: 3 givenname: Bridget surname: Candy fullname: Candy, Bridget organization: Royal Free Hospital – sequence: 4 givenname: Lloyd surname: Steele fullname: Steele, Lloyd organization: Wellcome Sanger Institute – sequence: 5 givenname: Clare surname: Reynolds fullname: Reynolds, Clare organization: School of Public Health, Physiotherapy and Sports Science, University College Dublin – sequence: 6 givenname: Beth surname: Stuart fullname: Stuart, Beth organization: University of Southampton – sequence: 7 givenname: Roses surname: Parker fullname: Parker, Roses organization: Cochrane MOSS Network, c/o Cochrane Pain Palliative and Supportive Care Group – sequence: 8 givenname: Emma surname: Axon fullname: Axon, Emma organization: Cochrane – sequence: 9 givenname: Amanda surname: Roberts fullname: Roberts, Amanda organization: Nottingham Support Group for Carers of Children With Eczema – sequence: 10 givenname: Megan surname: Doyle fullname: Doyle, Megan organization: University of Nottingham – sequence: 11 givenname: Derek K. orcidid: 0000-0001-8269-4496 surname: Chu fullname: Chu, Derek K. organization: McMaster University – sequence: 12 givenname: Masaki surname: Futamura fullname: Futamura, Masaki organization: National Hospital Organization Nagoya Medical Center – sequence: 13 givenname: Miriam surname: Santer fullname: Santer, Miriam organization: University of Southampton – sequence: 14 givenname: Hywel C. surname: Williams fullname: Williams, Hywel C. organization: University of Nottingham – sequence: 15 givenname: Suzie orcidid: 0000-0002-6113-1173 surname: Cro fullname: Cro, Suzie organization: Imperial College London – sequence: 16 givenname: Aaron M. surname: Drucker fullname: Drucker, Aaron M. organization: Women's College Hospital – sequence: 17 givenname: Robert J. orcidid: 0000-0002-4913-7580 surname: Boyle fullname: Boyle, Robert J. email: r.boyle@imperial.ac.uk organization: Imperial College London |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39219446$$D View this record in MEDLINE/PubMed |
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| Copyright | 2024 The Author(s). published by John Wiley & Sons Ltd. 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd. 2024. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Keywords | eczema network meta‐analysis calcineurin inhibitor systematic review topical steroid Janus kinase inhibitor |
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| License | Attribution 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
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| Notes | https://youtu.be/k7CU‐e4Jdpk This systematic review and network meta‐analysis was funded by the National Institute for Health and Care Research (NIHR) through a Research for Patient Benefit grant to Dr Robert Boyle (NIHR201993) and a Systematic Review Programme Grant to Cochrane Skin at the Centre of Evidence Based Dermatology. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding . This article includes Author Insights, a video abstract available at ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-4 content type line 23 ObjectType-Undefined-3 Funding: This systematic review and network meta‐analysis was funded by the National Institute for Health and Care Research (NIHR) through a Research for Patient Benefit grant to Dr Robert Boyle (NIHR201993) and a Systematic Review Programme Grant to Cochrane Skin at the Centre of Evidence Based Dermatology. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. This article includes Author Insights, a video abstract available at: https://youtu.be/k7CU‐e4Jdpk. |
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Objective
Eczema is the most burdensome skin condition worldwide and topical anti‐inflammatory treatments are commonly used to control symptoms. The... Eczema is the most burdensome skin condition worldwide and topical anti-inflammatory treatments are commonly used to control symptoms. The relative... ObjectiveEczema is the most burdensome skin condition worldwide and topical anti‐inflammatory treatments are commonly used to control symptoms. The relative... Trials of topical anti‐inflammatory eczema treatments are mostly industry‐funded, evaluate short‐term outcomes and carry a high risk of bias due to selective... |
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| SubjectTerms | Administration, Topical Anti-Inflammatory Agents - administration & dosage Anti-Inflammatory Agents - adverse effects Antibiotics calcineurin inhibitor Clinical trials Contact dermatitis Eczema Eczema - drug therapy Humans Inflammation Inhibitor drugs Janus kinase Janus kinase inhibitor Meta-analysis network meta‐analysis Phototherapy Randomized Controlled Trials as Topic Skin diseases Steroid hormones Steroids Systematic Review Tacrolimus Thinning topical steroid Treatment Outcome |
| Title | Topical Anti‐Inflammatory Treatments for Eczema: A Cochrane Systematic Review and Network Meta‐Analysis |
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