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2018 Alopecia Areata Research Summit: Summary of First Day

A review of key topics discussed on the first day of the 2018 Alopecia Areata Research Summit, Forging the Future, held December 4-5 in New York City.

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2018 Alopecia Areata Research Summit: Summary of First Day

  1. 1. Alopecia Areata Research Summit “Forging the Future” Summary of Day 1 DAVID A. NORRIS MD PROFESSOR AND CHAIRMAN DEPARTMENT OF DERMATOLOGY UNIVERSITY OF COLORADO
  2. 2. Alopecia Areata Research Summit “Forging the Future” Summary of Day 1 -Ten Years of Research Summits have focused the basic, clinical and translational research program -Based on clinical trials present at the last research summit, JAK inhibitors have been used widely in practices specializing in AA, with impressive effect. -Partnerships with multiple pharmaceutical companies promise to lead to a new generation of systemic and topical treatments for AA. - The historic success of NAAF in partnership with NIAMS has been expanded to include the partnership with the FDA , and clinical research organizations such as the International Dermatology Outcomes Measures and the Patient Reported Outcomes Consortium
  3. 3. Elaine Fuchs Coping with Stress: Stem Cells in Injury and Inflammation Stem Cells in the Hair Follicle bulge are susceptible to damage by multiple stresses: Mechanical, microbes and other pathogens, toxins insects and oncogenic wounds. The HF bulge and inner bulge are susceptible to damage that may stimulate the DP to initiate cycling of the HF and proliferation of the bulge stem cells. Damage to inner bulge adherens junctions may lead to inflammation involving Dendritic cells and Tregs, mediated by chemokines and NFkB. Similar inflammation and epithelial repair may also occur in the IFE. If this inflammation/immunity related to initiating AA?
  4. 4. Natasha Mesinkovska Summary of Preceding Alopecia Areata Research Summits -Founding Principle: Organize the NAAF-funded research program , coordinate with the NIH, get new hair investigators working on AA. -Results: 1. Research Summits communicate and facilitate research program 2. NIAMS-funded Registry for 20 years helped to organize basic and clinical research program 3. Results of genetics and immunologic research provided the bases for translational research program 4. New investigators , a clinical and translational research network were developed 5. Close organizational ties with NIH, FDA, Pharma
  5. 5. Angela Christiano Genetics and Immunology of Alopecia Areata Genetics and Immunology are central to understanding AA 3 new areas of research: 1. JAK critical in initiation of AA and in acquired immunity involving NKG2D+T cells , IL15 and IFNg 2. JAki may induce” immune exhaustion” (what a tumor does to T cell); k/o Jak 1/3 – increase markers of exhaustion including IFNg 3. Gut microbiome – Oral antibiotics block AA in C3H HeJ mice – affect gut microbiome, not skin microbiome -New AA pts show bidirectional dysbiosis • Firmicutes up, Bacteroides down •
  6. 6. Maria Hordinsky Current Treatment of Alopecia Areata A concise and knowledgeable review of treatment in AA JAKi becoming mainstream Rx Warmed about the long-term toxicities of chronic JAKi
  7. 7. Ralf Paus AA: Autoimmune Disease or Hair Follicle Response Pattern to Immunological Disease Alternative Mechanisms of AA: 1. Not all AA is due to Autoimmunity, Cytotoxic T cells, genetic control of acquired immunity 2. Do NKG2D+ NK cells respond to local triggers, causing gamma interferon storm, induction of Catagen, loss of Immune Privilege, and further cytotoxicity as a response to NK initiated inflammation? 3. Or is there only a subset of AA patients in whom there is autoimmunity?
  8. 8. Amos Gilhar Pre-Clinical Research in Vivo: Pros and Cons of the C3H/HEJ models versus the Humanized Mouse Model -C3H HeJ: TLR 7 -Humanized mouse: Human skin, Human NKG2D+ or C56+ cells Use humanized mouse model to screen drugs E.g. Apremilast protective but not therapeutic
  9. 9. Brittany Craiglow Jak INH for the Treatment of AA in the Pediatric Population -5 Publications addressing use of JAKi in AA Using Tofacitinib, Ruxolitinib, or Baracitinib - Effective in at least 50% of cases -Multiple ongoing trials now enrolling subjects 12-17 years old - Safety and efficacy needs to be determined in future investigations
  10. 10. Brett King Responses of Eyebrows and Eyelashes to Tofacitinib I Patients with Severe AA -Involvement of Brows and/or lashes in 76% of AA Patients -Reviewed records of AA patients treated with tofacitinib from 2014-2018 -98 patients with total scalp loss- 86% had improvement of eyebrows and lashes; complete regrowth of all sites in 16% - Regrowth of brows and lashes variable; can occur in subjects with AA > 10 years.
  11. 11. Melissa Peck Piliang Long-Term Treatment for Severe AA with Oral Tofacitinib -retrospective cohort of 20 patients -20% with AA totalis -60% received tofacitinib for at least 12 months -94% some regrowth; 60 % achieved SALT 50; 24% SALT 90 -35% had lab abnormalities; six clinical adverse events
  12. 12. Hind Almohanna Platelet-Rich Plasma in the Treatment of AA -Platelet derived GF, bind to stem cells -Increase BC-2; Bcat promote melanoblast, FGF7 -No consensus of standard approach 5 studies and some case reports IL PRP plus IL TAC produced hair regrowth in AA; not very useful in AA totalis or universalis -More larger studies needed
  13. 13. Jessica Lin In Vivo Imaging in Alopecia Areata Patients Using Multiphoton Microscopy MPM may be useful in non-invasive following of AA
  14. 14. Emma Guttman-Yassky Cytokine Targeted Treatments of Alopecia Areata -Th1 is believed to be central to AA; recent evidence suggests Th2 and IL-23 might contribute - AA and atopic dermatitis (AD) have phenotypic similarities - AD is highest comorbidity of AA - Initiating a new treatment paradigm for AA, using small molecules and targeted therapies for IL-4, IL- 13, IL31, IL23 - Dupilumab works, Ustekinumab does not
  15. 15. Mark Lebwohl AA: Lessons from Other Inflammatory Skin Diseases -Psoriasis has been a great model to dissect the immune pathways in inflammatory skin disease. Many similarities (but also differences) between immune response in Psoriasis and AA. -Cyclosporine -TNFa inh -IL 12/23 IL-17
  16. 16. T Cell Cytotoxicity Versus Inhibiting Cellular Pathways Pathway blockade JAKi – Inhibit IFN-g and IL15 pathways Cellular Cytotoxicity -Prednisone -Methotrexate -Ultraviolet radiation
  17. 17. Industry Panel -Representatives from 7 pharmaceutical companies: Aclaris, Bioniz, Concert, Lilly, Legacy, Leo, Pfizer - Committed to eliciting patient input in study design and outcomes and to help access - Discussion of problems in American Medicine; important dialogue for the future
  18. 18. Pfizer: 2 PDE4 inh for skin dz Jak1 Phase 3 Jak3 Phase 2 “Breakthrough” Tyk2/Jak1 : PS and AA Lilly: Severe AA Legacy: Botanicals Phase 2 Concert: TP543 Ruxolitinib Phase IIa Aclaris: “Soft JAKs” Topical JAKs Phase IIb Looking at sequence of Rx Bioniz: BN7-1 inh IL2, IL15, IL7 Industry Panel
  19. 19. Elise Olsen Objective Outcome Measures: Collecting Meaningful Data on AA -Discussed problems with developing accurate data on alopecia areata -Salt I -Salt II -ALODEX Canfield has made a tool for this -Global Score
  20. 20. Justin Ko The Importance of Eyebrows in the Treatment of Alopecia Areata Online survey of 1,741 AA patients Satisfaction with scalp and eyebrow regrowth is non-linear More subjects satisfied having complete eyebrows with no scalp hair (69%) than partial scalp hair (51%)
  21. 21. Dory Kranz AA: Patient Reported Outcome Consortium -Bringing patients into drug development process -AA PRO Industry Partners Leo Science and Technology Hub Aclaris Lilly PATIENT DERIVED OUTCOME MEASURE •PHASE I CONCEPT ELICITATION INTERVIEW •PHASE II TEST IN COMMUNITY •PHASE III VALIDATE IN CLINICAL TRIAL
  22. 22. Alice Gottlieb Lessons From the International Dermatology Outcomes Measure (IDEOM) “Don’t Get Mad…Get Data” • Develop validated and patient generated outcome measures; these must be included in clinical trials • Payers want outcomes that lead to lower cost; effects on patient productivity; make outcomes predictable; biomarker indicating response • Needs to decrease data input on EMR • Derm needs to demonstrate quality of the care we provide • Social media score • “If you are not at the table you are on the menu”.
  23. 23. Alopecia Areata Research Summit “Forging the Future” Summary of Day 1 -Ten Years of Research Summits have focused the basic, clinical and translational research program -Based on clinical trials present at the last research summit, JAK inhibitors have been used widely in practices specializing in AA, with impressive effect. -Partnerships with multiple pharmaceutical companies promise to lead to a new generation of systemic and topical treatments for AA. - The historic success of NAAF in partnership with NIAMS has been expanded to include the partnership with the FDA , and clinical research organizations such as the International Dermatology Outcomes Measures and the Patient Reported Outcomes Consortium

A review of key topics discussed on the first day of the 2018 Alopecia Areata Research Summit, Forging the Future, held December 4-5 in New York City.

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