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Current Treatment of Alopecia Areata

Overview of options available to treat pediatric and adult alopecia areata, including the risks and benefits of current and evolving off-label treatment options with the understanding that there is currently no treatment approved by the FDA for this disease.

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Current Treatment of Alopecia Areata

  1. 1. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Current Treatment of Alopecia Areata Maria Hordinsky, MD Professor and Chair Department of Dermatology University of Minnesota Minneapolis, Minnesota
  2. 2. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Alopecia Areata can present in adults and ..
  3. 3. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Alopecia Areata: Kids , all races, males and females at any age.
  4. 4. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Current Treatment: the Basics Figure out what really bothers the parents of a child with alopecia areata or the patient with alopecia areata – Is it scalp hair loss? – eyebrow loss? – eyelash loss? – nail issues? – beard hair loss? All of the above? – Is it that there is shedding every single day and seeing all the hair loss is depressing and anxiety provoking? – Is it dealing with recurrent hair loss despite treatment? – Other
  5. 5. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. History: – Hair care habits – – Pitfall: “I have no scalp hair so I stopped shampooing!” – Medications, previous therapies – Symptoms – pain, itch, burning, other – Body hair – is there too much or too little? – Nail abnormalities – Menstrual cycle/Pregnancies – Diet/Supplements – Family History – Questions about androgen excess, autoimmune/endocrine diseases – Effect of alopecia areata on daily activities, social interactions
  6. 6. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Activities Impacted by AA – 2017 (N=641)
  7. 7. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Clinical Examination SCALP • Document presence of vellus, indeterminate and terminal fibers • Presence or absence of scale, erythema (redness) folliculitis, atrophy BODY • Document eyebrow, eyelash or body hair loss NAILS • Document nail dystrophy, pitting, etc. • PEARL : Use photography or the SALT score or both
  8. 8. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Objective Outcome Measures: Collecting Meaningful Data on Alopecia Areata www.jaad.org/article/S0190-9622(17)32614-2/fulltext EliseA.OlsenMDaJanetRobertsMDbLeonardSperlingMDcAntonellaTostiMDdJerry ShapiroMDeAmyMcMichaelMDfWilmaBergfeldMDgValerieCallenderMDhParad iMirmiraniMDiKenWashenikMD,PhDejDavidWhitingMDkGeorgeCotsarelisMDl MariaHordinskyMDm • Currently the only standardized method of assessment of alopecia areata is the SALT score. • This article offers recommendations for standardized assessment and response criteria in patients with alopecia areata. • These methods will facilitate direct comparison of alopecia areata treatment outcomes in both clinical practice and clinical trials.
  9. 9. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. The % of hair loss in any one of the 4 quadrants of the scalp = % hair loss X % surface area in that quadrant In this example, hair loss raw scores equal: Left quadrant = 95% loss Top quadrant = 95% loss Right quadrant = 90% loss Back quadrant = 55% loss Each quadrant is multiplied by it’s respective surface area percent SALT score is the sum of the 4 quadrant scores 17.1 + 16.2 + 38 + 13.2 = 84.5 J Am Acad Dermatol 2004;51:440-7 Methodology
  10. 10. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Laboratory Tests Select based on the history and physical examination: – Thyroid Function Studies – Heme and Iron Profiles including serum ferritin and hemoglobin – If indicated, – Non cycle dependent hormones such as DHEA-S and total/free testosterone – ANA or other autoantibodies – “Nutrition Labs” including Vitamin D, Thiamine, Zinc, total protein, other
  11. 11. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Patients, parents of affected children and family members are eager to learn more about alopecia areata.
  12. 12. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. EPIDEMIOLOGY OF ALOPECIA AREATA • Affects 1.7-2.1% of the population • 50-80% of cases are sporadic • Disease associations may vary around the world and include vitiligo, thyroid disease, atopy (allergic rhinitis, asthma, atopic dermatitis) • Both males and females of all ages and races can be affected • Current genetic research suggests the same genes involved in alopecia areata also play a role in rheumatoid arthritis, type 1 diabetes, celiac disease.
  13. 13. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Inheritance of Alopecia Areata • A multifactorial condition Source: Greenwood Genetics Center
  14. 14. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Inheritance of Alopecia Areata Monozygotic (identical) twins Dizygotic (fraternal) twins Genes Shared 100% 50% Concordance Rates for AA 42-55% 0-10%
  15. 15. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. NORMAL HAIR CYCLE • Anagen –90% of follicles -lasts 2-7 years • Catagen – 1-2% of follicles – lasts 2-3 weeks • Telogen – Up to 10% of follicles – lasts 2-3 months
  16. 16. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Alopecia Areata Anagen Attack ↓ Anagen Arrest !
  17. 17. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. IMMUNOLOGY A hallmark of alopecia areata: – peribulbar lymphocytes around anagen follicles
  18. 18. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Histopathology: Normal Human Scalp: Horizontal Section
  19. 19. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. A17 02-0573 L
  20. 20. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. The Clinic Visit in 2018 - the Treatment Discussion A number of treatments can induce hair growth in AA but few have been tested in randomized controlled trials and there are few published data on long-term outcomes; most focus on hair regrowth.
  21. 21. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. In the absence of an approved treatment by the Federal Drug Administration, choosing a treatment for AA in children and adults takes into consideration several factors including: • age of the patient • location of the loss • disease extent • disease activity • presence of other medical problems • scalp biopsy report on the hair cycle, inflammation • patient/parent choice after a review of proposed treatment risks, benefits and expectations.
  22. 22. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. The Clinic Visit in 2018 - the Treatment Discussion • Patients and families have heard the “buzz” about potential new treatments for alopecia areata and the discussion needs to include a conversation about ongoing and future clinical research opportunities as well as off label use of janus kinase inhibitors.
  23. 23. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Janus Kinase (JAK) Family The janus kinase (JAK) family, including JAK1, JAK2, JAK3 and tyrosine-protein kinase (TYK2), is a group of cytoplasmic tyrosine kinases that mediate signal transduction via interactions with Type 1 and Type 2 cytokine receptors critical for leukocyte activation, proliferation, survival and function. • Patients and some physicians are eager to try this oral or topical off label therapeutic approach with the support of industry patient assistance programs, self-pay, or in some cases, insurance coverage.
  24. 24. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. The Clinic Visit in 2018 - the Treatment Discussion • In contrast, there are patients with long standing recalcitrant extensive AA who have tried and failed treatments or have elected not to treat their AA who view the emerging treatments and opportunities for clinical trial participation with interest and hope. • Such patients frequently make clinic visits to catch up on the latest information and many but not all are eager to join in clinical research activities.
  25. 25. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Review of where we were 2 years ago at the last Summit -
  26. 26. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Randomized Controlled Trials in Alopecia Areata We analyzed in PubMed “randomized controlled trials” “alopecia areata” and assessed the quality of the studies. Hordinsky M, Donati A. Alopecia areata: an evidence-based treatment update. Am J Clin Dermatol. 15:231-245, 2014.
  27. 27. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Results and Conclusions • Using the American College of Physicians Guideline grading system, the assessment was that the majority of these studies were only of moderate quality. • At the same time, a number of treatments were found to be effective, for example, topical and oral corticosteroids and the sensitizing agents diphenylcyclopropenone and dinitrochlorobenzene. • Most studies though had major limitations that hindered the interpretation of study results.
  28. 28. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. PATCHY ALOPECIA AREATA: TREATMENTS • Topical or Intralesional Corticosteroids • Minoxidil Solution- 2% or 5% • Anthralin • Combination Therapy • Steroids in Shampoo Formulations • Topical Immunotherapy
  29. 29. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. • Corticosteroids: – Topical – Intralesional – Pulsed methlypredisolone – Oral • Topical minoxidil • Topical immunotherapy – DPCP – SADBE • Dithranol • Phototherapy – PDT – PUVA – NBUVB – Laser therapy - Excimer laser/Fractional Photothermolysis Laser • Immunosuppresive agents – Methotrexate – Cyclosporine • Prostaglandin analogues • Biologics Treatments
  30. 30. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. November 14-15, 2016, Alopecia Areata Summit, New York City Building and Crossing the Translational Bridge Angela Christiano: Update on Genetics and Immunology • GWAS studies have provided at least 14 genes involved in AA. • Immunological studies have focused on the role of CD8+ T cells in mediating disease, and the use of JAK inhibitors to prevent and treat AA in the C3H/H3J mouse model. • These preclinical studies paved the way for early clinical investigation in patients, which has been done in several centers to date. • Gene expression studies have uncovered biomarker signatures that can be used to follow response to treatment.
  31. 31. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Success Stories: Lessons from Clinical Studies with JAK Inhibitors Dr. Julian Mackay-Wiggan: Update on Clinical Research in AA, Columbia University Ruxolitinib study – 12 patients, 20mg BID. Regrowth as early as 4 weeks. 9 of 12 had 50% regrowth.8 of 9 achieved their endpoint by week 12 (75% response rate). Tofacitinib study – 12 patients 5mg BID up to 10mg BID. Followed for 6 months. 7 of 12 had 50% regrowth. 6 of 7 responders needed dose escalation (approx. 65% response rate). Relapse 4-8 weeks after stopping. Dr. Wilma Bergfeld, MD: Cleveland Clinic AA Tofacitinib Results Open retrospective study. Moderate to severe, recalcitrant patients, some with RA and AA. Thirteen patients, all recalcitrant to other therapies. Average regrowth at 4 months, some as late as 9 months. Some on drug for 18 months. One AU patient was African American, regrew his eyebrows and lashes but not scalp and not body hair. Three patients had total regrowth. One was duration of 30 yrs. Response rate = approx. 54%. 2016 AA Research Summit
  32. 32. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Dr. Justin Ko: Oral Tofacitinib in Severe AA – Stanford/Yale Study All patients on 5mg BID and for 3 months duration only. Enrolled 70 patients – 66 finished study. Long durations 1-43 years; average 5 years duration. ¾ were AU/AT patients. Biomarker analysis using gene expression studies. Outside the study – treating approx. 80 patients. About 2/3 of patients grow clinically acceptable patients at 6 months or longer. Roughly 66% overall response rate. Dr. Brett King: Yale Study of Tofacitinib in AA in Adults and Adolescents Approx. 90 adult patients treated and 13 adolescents with tofacitinb alone or tofacitinb with pulse steroid. Overall response rate approx. 60% in adults, 75% in teenagers. Patients with disease duration less than 11 years have better responses. Relapses seen while on treatment, and after drug stopped. Topical studies treating one patient with compounded ruxolitinib, regrew brows. Three compounded tofacitinib formulations, no positive results.
  33. 33. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Today-
  34. 34. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Emerging Directions (2014) to the 2016 Summit to Emerged Therapies (2018) • Targeting intracellular protein kinases, such as the JAK family of tyrosine kinases - and in particular: • Ruxolitinab: JAK1/JAK2 inhibitor • Tofacitinib: JAK1/JAK3 inhibitor
  35. 35. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Case 1 History • 25-year-old female with a past medical history of Hashimoto’s thyroiditis and a 10-year history of patchy and extensive alopecia areata • Previous treatments have included multiple courses and trials of clobetaosl 0.05% shampoo, intralesional Kenalog injections, topical steroids, Rogaine, and oral prednisone. • Multiple family members have been diagnosed with rheumatoid arthritis (RA) and her father has extensive AA with RA
  36. 36. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. EM 9/4/15 (started tofacitnib 5 mg twice a day 8/2015)
  37. 37. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. EM 8/22/16 with ongoing improvement in 2018 but unable to discontinue her oral medication as the disease returns when she lowers her dose.
  38. 38. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Reason for Presentation • To – discuss JAK inhibitors as an emerging treatment for alopecia areata and update on current clinical trials – present a patient who has done well on tofacitinib 5 mg twice a day but who is unable to come off the medication as her disease flares – to discuss how “traditional therapies” are used to manage new patches of alopecia areata – role of topical JAK inhibitors provided by compounding pharmacies
  39. 39. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. KF, 63-year old, F
  40. 40. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 12/2/2016
  41. 41. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 3/25/2017
  42. 42. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 6/1/2017
  43. 43. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 12/11/2017
  44. 44. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 3/12/2018
  45. 45. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 6/19/2018
  46. 46. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. ASC, 8-year old, F
  47. 47. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 5/12/2015
  48. 48. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 1/23/2017
  49. 49. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 4/24/2017
  50. 50. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. 11/26/2018
  51. 51. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Current Treatment of Alopecia Areata: At the present time… • Most physicians generally prefer topical therapy for AA. • However, following the recently published studies in which primarily the Jak inhibitors Tofacitinib or Ruxolitinib were shown to reverse the alopecia areata process, there has been a surge of enthusiasm for using more aggressive systemic therapies including not only Tofacitinib and Ruxolitinib but also other JAK inhibitors. • Attention is also more focused on the psychological needs of patients with alopecia areata.
  52. 52. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Summary With all the current clinical research activities, the future is looking up for a disease that is common and currently has no FDA approved therapy And in the mean time, other therapies continue to be tested such as the following Simvastatin/Ezetimibe Photobiomodulation Platelet Rich Plasma Antihistamines Fecal Transplantation Other
  53. 53. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. Photobiomodulation - Mechanism of Action1 • PBM acts on mitochondria and alters cell metabolism via photodissociation of inhibitory NO from cytochrome c oxidase which in turn: – Increases ATP production – Modulates ROS – Inducing transcription factors (i.e., NFKB and HIF-1) • Increasing protein synthesis, triggering increased cell proliferation and migration, altering cytokine levels & growth factors, and increasing tissue oxygenation Photo obtained from: Avci P, Gupta A, Sadasivam M et al. Low-level laser (light) therapy (LLLT) in skin: stimulating, healing , restoring. Semin Cutan Med Surg. 2013;32(1):41-52.
  54. 54. University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. PBM Devices Currently Available for Home Use Image obtained from Dr. Ronda Farah’s Photobiomodulation Presentation at the 2017 AAD Annual Meeting
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Overview of options available to treat pediatric and adult alopecia areata, including the risks and benefits of current and evolving off-label treatment options with the understanding that there is currently no treatment approved by the FDA for this disease.

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