**Title:** A systematic review investigating the proportion of clinical images shared in prospective randomized controlled trials involving patients with atopic dermatitis and systemic pharmacotherapy Sam Polesie,1,2 and Mikael Alsterholm1,2,3 ¹Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ²Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden ³ Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden ## **Corresponding author:** Sam Polesie, MD, PhD Gröna stråket 16, SE-413 45 Gothenburg, Sweden Email: [sam.polesie@gu.se](mailto:sam.polesie@gu.se) **Table SI:** Data Extraction sheet **Table SII:** List of excluded records and reason for exclusion **Table SIII:** List of represented journals among all included investigations **Appendix S1:** PRISMA Checklist **Appendix S2:** Search string for PubMed **Appendix S3:** Reference list of excluded records # **Table SI – Data Extraction sheet.** DOI, Digital Object Identifier. | First
Year
author | Journal | DOI-link | Primary
outcome | Time to primary
outcome | Number of randomized
patients | Number of patients depicted
in manuscript | Number of patient images
in manuscript | Number of patients depicted
in supplements | Number of patient images
in supplements | Video
Supplement | Number of patients depicted
in video supplements | Number of images depicted
in video supplements | Comments | |-------------------------|---------|----------|--------------------|----------------------------|----------------------------------|----------------------------------------------|-------------------------------------------|-----------------------------------------------|--------------------------------------------|---------------------|-----------------------------------------------------|---------------------------------------------------|----------| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | ## **Table SII – List of excluded records and reason for exclusion** | First author | Year | Reason for exclusion | Journal | |------------------------|------|-------------------------|------------------------------| | Bangert, et al. | 2023 | Wrong study drug | J Invest Dermatol | | Cork, et al. | 2020 | Wrong outcome | Br J Dermatol | | Cork, et al. | 2021 | Wrong outcome | Br J Dermatol | | Granlund, et al. | 1997 | Wrong outcome | Acta Derm Venereol | | Guttman-Yassky, et al. | 2023 | Post-hoc | J Eur Acad Dermatol Venereol | | Irvine, et al. | 2018 | Wrong publication type | Br J Dermatol | | Katoh, et al. | 2022 | Wrong outcome | JAAD Int | | Rossi, et al. | 2021 | Wrong publication type | Dermatology | | Siegfried, et al. | 2023 | Post-hoc | Dermatol Ther (Heidelb) | | Silverberg, et al. | 2022 | Extension investigation | J Allergy Clin Immunol | | Thaci, et al. | 2019 | Post-hoc | J Dermatol Sci | Acta Derm Venereol, Acta Dermato-Venereologica; Br J Dermatol, British Journal of Dermatology; Dermatol Ther (Heidelb), Dermatologic Therapy (Heidelberg); Dermatology, Dermatology; J Allergy Clin Immunol, Journal of Allergy and Clinical Immunology; JAAD Int, Journal of the American Academy of Dermatology International; J Dermatol Sci, Journal of Dermatological Science; J Eur Acad Dermatol Venereol, Journal of the European Academy of Dermatology and Venereology; J Invest Dermatol, Journal of Investigative Dermatology. ### **Table SIII – List of represented journals among all included investigations.** | Journal abbreviation | Full journal name | |-----------------------------------|----------------------------------------------------------| | Acta Derm Venereol | Acta Dermato-Venereologica | | Br J Dermatol | British Journal of Dermatology | | Clin Exp Allergy | Clinical and Experimental Allergy | | Contact Dermatitis | Contact Dermatitis | | Dermatitis | Dermatitis | | Dermatol Ther | Dermatologic Therapy | | Dermatology | Dermatology | | Eur J Pediatr | European Journal of Pediatrics | | Front Med (Lausanne) | Frontiers in Medicine | | Indian J Dermatol Venereol Leprol | Indian Journal of Dermatology, Venereology and Leprology | | Iran J Allergy Asthma Immunol | Iranian Journal of Allergy, Asthma and Immunology | | J Allergy Clin Immunol | Journal of Allergy and Clinical Immunology | | J Allergy Clin Immunol Pract | Journal of Allergy and Clinical Immunology: In Practice | | J Am Acad Dermatol | Journal of the American Academy of Dermatology | | J Dermatol | The Journal of Dermatology | | JAMA Dermatol | Journal of the American Medical Association Dermatology | | Lancet | The Lancet | | N Engl J Med | New England Journal of Medicine | ### **Supplementary Appendix 1 – PRISMA Checklist** | Section and Topic | Item
# | Checklist item | Location
where item is
reported | |----------------------------------|-----------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------| | TITLE | | | | | Title | 1 | Identify the report as a systematic review. | Included | | ABSTRACT | | | | | Abstract | 2 | See the PRISMA 2020 for Abstracts checklist. | Abstract | | INTRODUCTION | | | | | Rationale | 3 | Describe the rationale for the review in the context of existing knowledge. | Introduction | | Objectives | 4 | Provide an explicit statement of the objective(s) or question(s) the review addresses. | Introduction | | METHODS | | | | | Eligibility criteria | 5 | Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses. | Methods | | Information
sources | 6 | Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when
each source was last searched or consulted. | Methods | | Search strategy | 7 | Present the full search strategies for all databases, registers and websites, including any filters and limits used. | Appendix S2 | | Selection process | 8 | Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each
report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. | Methods | | Data collection
process | 9 | Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked
independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. | Methods | | Data items | 10a | List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were
sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect. | Methods
Table SI | | | 10b | List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions
made about any missing or unclear information. | Not applicable | | Study risk of bias
assessment | 11 | Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and
whether they worked independently, and if applicable, details of automation tools used in the process. | Not applicable
and Methods | | Effect measures | 12 | Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results. | Not applicable | | Synthesis methods | 13a | Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing
against the planned groups for each synthesis (item #5)). | Methods | | | 13b | Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. | Not applicable | | | 13c | Describe any methods used to tabulate or visually display results of individual studies and syntheses. | Methods | | Section and Topic | Item
# | Checklist item | Location
where item is
reported | | | | |----------------------------------|-----------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------|--|--|--| | | 13d | Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s),
method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used. | Not applicable | | | | | | 13e | Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression). | Not applicable | | | | | | 13f | Describe any sensitivity analyses conducted to assess robustness of the synthesized results. | Not applicable | | | | | Reporting bias
assessment | 14 | Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). | Not applicable | | | | | Certainty
assessment | 15 | Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. | | | | | | RESULTS | | | | | | | | Study selection | 16a | Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the
review, ideally using a flow diagram. | Figure 1 | | | | | | 16b | Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. | Not applicable | | | | | Study
characteristics | 17 | Cite each included study and present its characteristics. | Results | | | | | Risk of bias in
studies | 18 | Present assessments of risk of bias for each included study. | Not applicable | | | | | Results of
individual studies | 19 | For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g.
confidence/credible interval), ideally using structured tables or plots. | Results | | | | | Results of | 20a | For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies. | Not applicable | | | | | syntheses | 20b | Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g.
confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. | Results | | | | | | 20c | Present results of all investigations of possible causes of heterogeneity among study results. | Not applicable | | | | | | 20d | Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results. | Not applicable | | | | | Reporting biases | 21 | Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed. | Not applicable | | | | | Certainty of
evidence | 22 | Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed. | Not applicable | | | | | DISCUSSION | | | | | | | | Discussion | 23a | Provide a general interpretation of the results in the context of other evidence. | Discussion | | | | | | 23b | Discuss any limitations of the evidence included in the review. | Discussion | | | | | | 23c | Discuss any limitations of the review processes used. | Discussion | | | | Polesie *et al* Supporting material 8 | Section and Topic | Item
# | Checklist item | Location
where item is
reported | |------------------------------------------------------|-----------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------| | | 23d | Discuss implications of the results for practice, policy, and future research. | Discussion | | OTHER INFORMATION | | | | | Registration and | 24a | Provide registration information for the review, including register name and registration number, or state that the review was not registered. | Not applicable | | protocol | 24b | Indicate where the review protocol can be accessed, or state that a protocol was not prepared. | Not applicable | | | 24c | Describe and explain any amendments to information provided at registration or in the protocol. | Not applicable | | Support | 25 | Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review. | Funding | | Competing
interests | 26 | Declare any competing interests of review authors. | Attached
documents | | Availability of data,
code and other
materials | 27 | Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies;
data used for all analyses; analytic code; any other materials used in the review. | Table SI | *From:* Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, *et al.* The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71 ### **Supplementary Appendix 2 – Search strings for Medline (PubMed)** The search below included records from inception to December 21, 2023. #### **Medline (PubMed)** ("Randomized Controlled Trial"[pt] OR random\*) AND ("atopic dermatitis" OR "atopic eczema" OR "neurodermatitis" OR "eczema") AND (dupilumab OR tralokinumab OR upadacitinib OR abrocitinib OR baricitinib OR methotrexate OR azathioprine OR cyclosporine OR mycophenolate mofetil) ### **Supplementary Appendix 3 – Reference list of excluded records listed in alphabetical order** Bangert C, Loesche C, Skvara H, et al. IgE Depletion with Ligelizumab Does Not Significantly Improve Clinical Symptoms in Patients with Moderate-to-Severe Atopic Dermatitis. J Invest Dermatol 2023; 143: 1896-1905 e1898. Cork MJ, Thaci D, Eichenfield LF, et al. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol 2020; 182: 85-96. Cork MJ, Thaci D, Eichenfield LF, et al. Dupilumab provides favourable long-term safety and efficacy in children aged >/= 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study. Br J Dermatol 2021; 184: 857-870. Granlund H, Erkko P, Reitamo S. Comparison of the influence of cyclosporine and topical betamethasone-17,21-dipropionate treatment on quality of life in chronic hand eczema. Acta Derm Venereol 1997; 77: 54-58. Guttman-Yassky E, Silverberg JI, Thaci D, et al. Upadacitinib treatment withdrawal and retreatment in patients with moderate-to-severe atopic dermatitis: Results from a phase 2b, randomized, controlled trial. J Eur Acad Dermatol Venereol 2023; 37: 2558-2568. Irvine AD, Jones AP, Beattie P, et al. A randomized controlled trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT). Br J Dermatol 2018; 179: 1297-1306. Katoh N, Ohya Y, Murota H, et al. A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysis. JAAD Int 2022; 6: 27-36. Rossi M, Rovati C, Arisi M, et al. A Short Cycle of Narrow-Band UVB Phototherapy in the Early Phase of Dupilumab Therapy Can Provide a Quicker Improvement of Severe Atopic Dermatitis. Dermatology 2021; 237: 407-415. Siegfried EC, Simpson EL, Cork MJ, 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; 13: 1987-2000. Silverberg JI, de Bruin-Weller M, Bieber T, et al. Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results. J Allergy Clin Immunol 2022; 149: 977-987 e914. Thaci D, E LS, Deleuran M, et al. Efficacy and safety of dupilumab monotherapy in adults with moderateto-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). J Dermatol Sci 2019; 94: 266-275.