Epithelial-mesenchymal transition: an organizing principle of mammalian regeneration.

Introduction: The MRL mouse strain is one of the few examples of a mammal capable of healing appendage wounds by regeneration, a process that begins with the formation of a blastema, a structure containing de-differentiating mesenchymal cells. HIF-1α expression in the nascent MRL wound site blastema is one of the earliest identified events and is sufficient to initiate the complete regenerative program. However, HIF-1α regulates many cellular processes modulating the expression of hundreds of genes. A later signal event is the absence of a functional G1 checkpoint, leading to G2 cell cycle arrest with increased cellular DNA but little cell division observed in the blastema. This lack of mitosis in MRL blastema cells is also a hallmark of regeneration in classical invertebrate and vertebrate regenerators such as planaria, hydra, and newt. Results and discussion: Here, we explore the cellular events occurring between HIF-1α upregulation and its regulation of the genes involved in G2 arrest (EVI-5, γH3, Wnt5a, and ROR2), and identify epithelial-mesenchymal transition (EMT) (Twist and Slug) and chromatin remodeling (EZH-2 and H3K27me3) as key intermediary processes. The locus of these cellular events is highly regionalized within the blastema, occurring in the same cells as determined by double staining by immunohistochemistry and FACS analysis, and appears as EMT and chromatin remodeling, followed by G2 arrest determined by kinetic expression studies.

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021.

Since the second version of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations were published in 2015, therapeutic options for psoriatic arthritis (PsA) have advanced considerably. This work reviews the literature since the previous recommendations (data published 2013-2020, including conference presentations between 2017 and 2020) and reports high-quality, evidence-based, domain-focused recommendations for medication selection in PsA developed by GRAPPA clinicians and patient research partners. The overarching principles for the management of adults with PsA were updated by consensus. Principles considering biosimilars and tapering of therapy were added, and the research agenda was revised. Literature searches covered treatments for the key domains of PsA: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis; additional searches were performed for PsA-related conditions (uveitis and inflammatory bowel disease) and comorbidities. Individual subcommittees used a GRADE-informed approach, taking into account the quality of evidence for therapies, to generate recommendations for each of these domains, which were incorporated into an overall schema. Choice of therapy for an individual should ideally address all disease domains active in that patient, supporting shared decision-making. As safety issues often affect potential therapeutic choices, additional consideration was given to relevant comorbidities. These GRAPPA treatment recommendations provide up-to-date, evidence-based guidance on PsA management for clinicians and people with PsA.

International Dermatology Outcome Measures (IDEOM): Report from the 2020 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) initiative is a non-profit organization that aims to develop evidence-based outcome measurements to evaluate the impact of treatments for patients with dermatological disease. IDEOM includes all key stakeholders in dermatology (patient, physician, industry, insurer, and government) during the process of developing such outcome measurements. SUMMARY: Here, we provide an update of IDEOM activities that were presented at the 2020 IDEOM Virtual Annual Meeting (October 23-24, 2020). During the meeting, multiple IDEOM workgroups (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) shared their progress to date, as well as future directions in developing and validating Patient-Reported Outcome Measures. Updates on demonstrating efficacy in clinicals trials by the US Food and Drug Administration are also summarized. KEY MESSAGES: In this report, we summarize the work presented by each IDEOM workgroup (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) at the 2020 IDEOM Virtual Annual Meeting.

Examination of Treatment Satisfaction Instruments in Psoriasis: 2017 Results from the Psoriasis Working Group of the International Dermatology Outcome Measures (IDEOM).

BACKGROUND/AIMS: In dermatology clinical trials, assessment of patients' treatment satisfaction is crucial but often lacking. To address this need, IDEOM's Psoriasis Working Group seeks to evaluate, develop, and validate treatment satisfaction instruments for the psoriasis population. The Psoriasis Working Group aimed to determine (1) factors affecting psoriasis patients' satisfaction with their therapies, (2) adequacy of two commonly used generic treatment satisfaction instruments in reflecting the psoriasis patients' perspective, and (3) whether a need exists to develop a new treatment satisfaction instrument. METHODS: Patient perspectives on satisfaction with treatment efficacy, safety, convenience, and overall satisfaction were elicited.Stakeholders were presented with information regarding the feasibility and content validity of two generic treatment instruments, the Treatment Satisfaction Questionnaire for Medication (TSQM) and the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q). We conducted a nominal group discussion and survey to determine whether stakeholders considered these instruments feasible and adequate to address treatment satisfaction for psoriasis therapies. RESULTS: Forty-five stakeholders participated in the nominal group discussion and survey. 53% of participants voted that the TSQM and SATMED-Q are not adequate and that we should create a new dermatology-specific treatment satisfaction instrument. Patients and other stakeholders also provided feedback on aspects of treatment satisfaction important to them. These include speed of onset and durability of therapeutic effect of a medication, permanence of side effects, and convenience of administering the medication. CONCLUSION: Stakeholders, including patients and providers, determined that generic treatment satisfaction questionnaires are not adequate to evaluate treatment satisfaction in psoriasis patients.

Report from the International Dermatology Outcome Measures Initiative.

The International Dermatology Outcome Measures is a nonprofit organization dedicated to developing evidence-based, patient-centered outcome measures for dermatologic conditions. At the 2018 Alopecia Areata Research Summit, Dr Gottlieb, President of the International Dermatology Outcome Measures, presented an overview of their work in psoriasis, hidradenitis suppurativa, acne, and eczema and discussed the potential areas of mutual interest with the National Alopecia Areata Foundation. Herein, we present a summary of the topics discussed.

Investigator and Patient Global Assessment Measures for Psoriasis Clinical Trials: A Systematic Review on Measurement Properties from the International Dermatology Outcome Measures (IDEOM) Initiative.

BACKGROUND AND OBJECTIVE: The International Dermatology Outcome Measures (IDEOM) has defined a core set of domains to be measured in all psoriasis clinical trials. This set comprises the following domains: skin manifestations, psoriasis and psoriatic arthritis symptoms, health-related quality of life, investigator global, patient global, and treatment satisfaction. The next step is to define how to measure these domains. The objective of this article was to evaluate the quality of available instruments to assess 'investigator global' and 'patient global' domains to identify the most appropriate instruments. METHODS: Reviewers conducted a systematic literature review to retrieve studies on the measurement properties of instruments including either an investigator global assessment or a patient global assessment. Following the COnsensus based standards for the Selection of health Measurement INstruments (COSMIN) checklist, three independent reviewers rated the quality of each study. We then performed a qualitative synthesis of the evidence. RESULTS: We identified nine investigator global assessments and three patient global assessments, reflecting substantial variability in global assessment instruments. Overall, most measures lacked evidence for content validity and feasibility. The Lattice System-Physician Global Assessment, Product of the Investigator Global Assessment and Body Surface Area, and the professional-Simplified Psoriasis Index had higher levels of evidence for validity, reliability, and/or responsiveness than the 5- and 6-point investigator global assessments. The self-assessment-Simplified Psoriasis Index was the only patient global assessment with evidence for validity, reliability, and responsiveness. CONCLUSIONS: The 5- and 6-point investigator global assessments, which are the most widely used investigator global assessments in registered clinical trials, have less evidence for measurement properties as compared with the Lattice System-Physician Global Assessment, professional-Simplified Psoriasis Index, and the Product of the Investigator Global Assessment and Body Surface Area. However, all instruments lack evidence for content validity and feasibility. Further validation studies of investigator global assessments and patient global assessments are required to recommend the best global measure for psoriasis clinical trials.

Measuring psoriatic arthritis symptoms: A core domain in psoriasis clinical trials.

BACKGROUND: The International Dermatology Outcome Measures established a set of core domains to be measured in all psoriasis trials. This set requires that symptoms of psoriatic arthritis (PsA) be measured in all psoriasis studies. OBJECTIVE: To identify the approach to PsA screening and the most appropriate outcome measure for capturing PsA symptoms. METHODS: Following guidelines (ie, the COnsensus-based Standards for the selection of health Measurement INstruments, Core Outcome Measures in Effectiveness Trials Initiative, and Outcome Measures in Rheumatology Handbook), we conducted a consensus-building study that included patients, physicians, industry partners, and patient association representatives. The process consisted of a literature review and quality appraisal of measures for PsA symptoms, a pre-Delphi exercise, a Delphi survey, and a consensus meeting. RESULTS: Among the 297 expert participants in the Delphi survey, 87.5% agreed that all patients in a psoriasis trial should be screened for PsA with a validated screening tool. Regarding the measurement of PsA symptoms, the preferred instrument was the Psoriatic Arthritis Impact of Disease-9 (PsAID9), with the Routine Assessment Patient Index Data-3 (RAPID3) representing an acceptable alternative. LIMITATIONS: Only International Dermatology Outcome Measures members participated in the consensus meeting. CONCLUSION: The overwhelming majority of expert stakeholders agreed that all psoriasis trial participants should be screened for PsA, with PsA symptoms measured by using PsAID9 (or alternatively with RAPID3).

A provider global assessment quality measure for clinical practice for inflammatory skin disorders.

In our evolving health care system, dermatologists are increasingly being asked to prove the value of care they provide to patients with severe skin diseases. Current quality measures for inflammatory dermatoses have limited validity and feasibility. Through collaboration and a modified Delphi process, International Dermatology Outcome Measures and the American Academy of Dermatology sought to reach consensus on a valid and feasible provider-assessed global disease severity metric to be incorporated into a quality measure for inflammatory dermatoses. To inform the modified Delphi process, a review of the literature was performed, and data were collected on current provider-assessed global disease severity metrics. After literature review, 36 members of International Dermatology Outcome Measures and the American Academy of Dermatology participated in the modified Delphi process to reach consensus on features of the metric. Psoriasis, atopic dermatitis, and acne achieved overwhelming consensus for inflammatory dermatoses that could be measured in a global disease severity metric. Consensus was also reached on the use of a 5-point ordinal scale with descriptors provided through referenced electronic platforms. Expert development of quality measures incorporating this metric and its inclusion in data collection platforms are critical to enabling dermatologists to prove the value of care provided to patients with severe inflammatory dermatoses.

Achieving international consensus on the assessment of psoriatic arthritis in psoriasis clinical trials: an International Dermatology Outcome Measures (IDEOM) initiative.

Psoriatic arthritis (PsA) is rarely assessed in psoriasis randomized controlled trials (RCT); thus, the effect of psoriasis therapy on PsA is unknown. The International Dermatology Outcome Measures (IDEOM) has included "PsA Symptoms" as part of the core domains to be measured in psoriasis RCT. This study aimed to achieve consensus about screening for PsA and how to measure for "PsA Symptoms" in psoriasis RCT. At the IDEOM 2017 Annual Meeting, stakeholders voted on the role of PsA screening in psoriasis RCT. To select measures for "PsA Symptoms", we adapted the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. Three potential measures were selected. At the meeting, stakeholders voted on the validity, feasibility, and responsiveness of these measures. Of the 47 stakeholders, 93% voted that all psoriasis trial participants should be screened for PsA. "PsA Symptoms" measures included Patient Global (PG)-arthritis, Routine Assessment Patient Index Data (RAPID)-3, and Psoriatic Arthritis Impact of Disease (PsAID)-9. During the voting, more than 50% of the voters agreed that RAPID3 and PsAID9 were good measures for PsA Symptoms, able to capture all its essential elements. PsAID9 was considered the most feasible instrument, followed by RAPID3 and PG-arthritis, respectively. Finally, most participants agreed that RAPID3 and PsAID9 were responsive measures. Most study participants voted that all subjects in a psoriasis clinical trial should be screened for PsA. RAPID3 and PsAID9 outperformed PG-arthritis in measuring PsA Symptoms. This will be followed by a Delphi survey involving a larger stakeholder group.

Are Your Patients Satisfied A Systematic Review of Treatment Satisfaction Measures in Psoriasis.

Treatment satisfaction is paramount to the field of dermatology. Treatment dissatisfaction directly impacts patient outcomes and health care delivery. A critical need exists for standardized, validated treatment satisfaction measures in dermatology. Comprehensive evaluation of the performance of treatment satisfaction instruments used in psoriasis is lacking. We sought to critically appraise the literature on measurement properties of treatment satisfaction instruments used in psoriasis. We performed a systematic review to identify treatment satisfaction instruments used in psoriasis and corresponding studies on their measurement properties. We followed the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology to inform a best evidence synthesis. Eleven instruments were identified. Six achieved positive content validity ratings, 2 achieved positive reliability and structural validity ratings, and 1 achieved a positive internal consistency rating. The REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) and the Spanish Satisfaction With Treatment of Psoriasis Questionnaire (SSWTPQ) had the highest overall performance. Measurement property data for treatment satisfaction instruments were found to be insufficient in identifying a single best treatment satisfaction instrument for psoriasis. Additional studies are required to better characterize the measurement properties of treatment satisfaction measures and allow for standardized assessments across psoriasis clinical trials and clinical practice.

The Patient Research Partner Network Matures: A Report from the GRAPPA 2017 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has reached the third of 5 stages of organizational maturity regarding incorporating patient research partners (PRP) into psoriatic arthritis (PsA) and psoriasis research and educational efforts. Herein, we report the involvement of PRP at the GRAPPA 2017 annual meeting and plans for future PRP engagement.

Identifying a Core Domain Set to Assess Psoriasis in Clinical Trials.

Importance: There is no consensus on which domains should be measured or which instruments should be used in clinical trials for psoriasis therapies. Objective: To achieve international consensus among psoriasis stakeholders on a core set of domains that should be measured in all psoriasis clinical trials. Design, Setting, and Participants: Literature review, pre-Delphi survey exercises, nominal group discussions, and audience voting at 4 stakeholder meetings were used to develop candidate domains for 2 rounds of a Delphi survey. Stakeholders were patients or advocates of patients with psoriasis and health care professionals (HCPs) with expertise in psoriasis, including physicians, scientists, advocacy organization representatives, and regulators. Delphi surveys were conducted electronically from October through December 2015 and between September and October 2016. Stakeholder discussions with audience response voting were conducted at live meetings in the United States, Canada, and Italy from January 2013 to December 2016 to refine and ratify the core set of domains. Main Outcomes and Measures: Two rounds of an electronic Delphi survey were used to determine consensus. A domain was considered "core" (ie, should be measured in all trials) if a threshold consensus of at least 70% was met in both patient and HCP groups. Domains meeting consensus in only 1 group were considered to be important but were not required to be measured in all trials ("middle ring"). These domains were included for rerating in round 2. Domains that did not meet consensus in either of the groups ("outer ring") were considered to be of uncertain importance and were placed in the research agenda. Results: In round 1 of the Delphi survey, 107 HCPs and 14 patients participated. Most HCPs (72 [67%]) were dermatologists between 46 and 64 years old (71 [66%]), white (78 [73%]), and male (75 [70%]) from North America (60 [57%]) and Europe (34 [32%]).There were 10 pharmaceutical industry clinical or health economic scientists, 3 advocacy organization representatives, 2 regulatory agency representatives, and 5 "other." In the second round, 77 HCPs and 15 patients participated. Of the 20 candidate domains, the following 6 met consensus as core domains: skin manifestations, psoriasis and psoriatic arthritis symptoms, health-related quality of life, investigator global assessment, patient global assessment, and treatment satisfaction. Secondary skin manifestations as well as nail, inverse, genital, and guttate psoriasis were classified as important but not mandatory. Psoriatic arthritis signs, work productivity or participation, economic impact (direct and indirect cost), and cardiovascular disease comprised the research agenda. Conclusions and Relevance: This iterative Delphi process yielded international consensus among professional and patient stakeholders on 6 domains that should be measured in all clinical trials for psoriasis. Future International Dermatology Outcome Measures group efforts will focus on development of a core outcome measurement set for psoriasis trials.

Patient-Reported Outcome Measures for Pediatric Psoriasis: A Systematic Review and Critical Appraisal from International Dermatology Outcome Measures (IDEOM).

Childhood onset psoriasis has a profound impact on the development and quality of life of pediatric patients. Consequently, validated patient-reported outcome measures (PROMs) for pediatric psoriasis are vital to patient care. We sought to critically appraise the literature on the measurement properties of PROMs used in the pediatric psoriasis population. We performed a 2-stage systematic literature synthesis in MEDLINE (1950-2017) and EMBASE (1947-2017) to identify PROMs and studies evaluating their measurement properties. Analysis of studies followed the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology to inform a best evidence synthesis. From 1,128 articles, we identified 29 PROMs. Subsequently, we identified 8 studies evaluating the measurement properties of 7 instruments. Among these instruments, the Simplified Psoriasis Index (SPI) achieved a positive rating for criterion validity, the Dutch version of the Children's Dermatology Life Quality Index (CDLQI) achieved a positive rating for hypothesis testing, and the Swedish version of the CDLQI achieved a negative rating for hypothesis testing. All other assessed measurement properties received indeterminate or unknown ratings due to flaws in study design. PROMs are paramount to the management of pediatric psoriasis. This synthesis emphasizes the critical need for additional studies to further describe the measurement properties of PROMs used in pediatric psoriasis and identify validated, standardized measures for use in clinical practice and research.

National Psoriasis Foundation Priorities for Patient-Centered Research: Proceedings from the 2016 Conference.

The National Psoriasis Foundation (NPF) is developing an agenda for patient-centered research to help patients and their caregivers make more informed health care decisions by engaging psoriasis patients in prioritizing comparative effectiveness research (CER) topics. The NPF has created a novel patient-centered research platform known as Citizen Pscientist (CP), allowing patients with psoriasis and psoriatic arthritis to register and contribute their health data. The CP Governance Council administered an online 23-question CER survey to the CP community and held a structured meeting on December 3, 2016, with patients and researchers to review CER survey results and discuss patient-centered research priorities. Of the 2,945 patients surveyed, 792 patients responded. Three CER topics were deemed to be of high priority for the research agenda: 1) Treat-to-target therapy for psoriasis, 2) Psoriatic arthritis screening questionnaires for early detection and treatment of psoriatic arthritis, and 3) Comparative effectiveness of home-based phototherapy for psoriasis.

International Dermatology Outcome Measures (IDEOM) Group 2016 New York Meeting: Meeting Summary and Data from the Psoriasis Working Group.

The International Dermatology Outcome Measures (IDEOM) Group was established to develop validated and standardized patient-centered outcome measures in dermatology that meet the needs of stakeholders and can be used in clinical practice as well as clinical research. At this meeting, we aimed to define the final core domain set to be assessed in psoriasis clinical research and to identify which of the current psoriasis assessment instruments appropriately address those domains. Specifically, we sought to ascertain stakeholder input on domain match and feasibility of multiple psoriasis instruments. We presented 19 physician-reported and 23 patient-reported outcome measures at the meeting. Stakeholders anonymously voted on the validity and feasibility of each instrument. Validity was rated as: green (good), amber (fair), red (poor), and white (not enough information). Feasibility was rated as: green (feasible), amber (concerns about some aspects of feasibility), red (not feasible), and white (not enough information). Eighteen physician-reported and 20 patient-reported instruments received a favorable green or amber rating for validity from the majority of voters. Seventeen physician-reported and 19 patient-reported instruments received a green or amber rating for feasibility from the majority of voters. A significant proportion of the psoriasis instruments received a good or fair vote for measuring their intended psoriasis domains in a feasible manner. We will continue to refine our voting methodology and incorporate patient input into our process of defining psoriasis domains and developing validated instruments.

J Drugs Dermatol. 2017;16(8):770-777.

Defining Outcome Measures for Psoriasis: The IDEOM Report from the GRAPPA 2016 Annual Meeting.

The International Dermatology Outcome Measures (IDEOM) psoriasis working group was established to develop core domains and measurements sets for psoriasis clinical trials and ultimately clinical practice. At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the IDEOM psoriasis group presented an overview of its progress toward developing this psoriasis core domain set. First, it summarized the February 2016 meeting of all involved with the IDEOM, highlighting patient and payer perspectives on outcome measures. Second, the group presented an overview of the consensus process for developing the core domain set for psoriasis, including previous literature reviews, nominal group exercises, and meeting discussions. Future plans include the development of working groups to review candidate measures for at least 2 of the domains, including primary pathophysiologic manifestations and patient-reported outcomes, and Delphi surveys to gain consensus on the final psoriasis core domain set.

Defining Outcome Measures for Psoriatic Arthritis: A Report from the GRAPPA-OMERACT Working Group.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group recently published the updated 2016 psoriatic arthritis (PsA) core domain set, a set of disease features that should be measured in all clinical trials. At the GRAPPA annual meeting in July 2016, the PsA working group presented the updated PsA core domain set endorsed by 90% of participants at OMERACT in May 2016 and drafted a roadmap for the development of the PsA core outcome measurement set. In this manuscript, we review the development process of the PsA core domain set and the ongoing and proposed work streams for development of a PsA core measurement set.

Tackling Patient Centricity: A Report from the GRAPPA 2016 Annual Meeting.

In line with the global trend to have disease-related organizations be more patient-centric in their approach, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has made substantial progress incorporating patient research partners (PRP) into psoriatic arthritis and psoriasis research. Herein we summarize the involvement of PRP at the GRAPPA 2016 annual meeting. Plans for future PRP engagement were also discussed.

The International Dermatology Outcome Measures (IDEOM) Initiative: A Review and Update.

The International Dermatology Outcome Measures (IDEOM) group, comprising patients, physicians, health economists, industry partners, payers, and regulatory agencies, was established to develop unified and validated patient-centered outcome measures in dermatology in response to increasing demand to quantify effectiveness of treatments and performance outcomes among providers. IDEOM has chosen to start with psoriasis outcome measures, and then apply its methodology to other dermatologic diseases. In this paper, we review the background and progress to date of IDEOM, including an update of IDEOM activities as of our 2016 meeting in Washington DC, USA. Briefly, the progress-to-date of a Delphi process to create outcome measures for psoriasis was reviewed, including preliminary data from the first round of Delphi voting. Updates were also heard from industry partners including the National Psoriasis Foundation (NPF) and the US Food and Drug Administration (FDA). Furthermore, plans to establish outcome measures for hidradenitis suppurativa (HS) were discussed.

J Drugs Dermatol. 2017;16(2):119-124.