Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata

• ClinicalTrials.gov Identifier: NCT03800979
• Recruitment Status: Active, not recruiting
• First Posted: January 11, 2019
• Last Update Posted: February 11, 2020
• Sponsor: Institute of Dermatology, Thailand
• Information provided by (Responsible Party): Chinmanat Tangjaturonrusamee, Institute of Dermatology, Thailand

Study Description

Brief Summary:

The objective of this study is to assess the safety and efficacy of Tofacitinib in treating patients with extensive and recalcitrant Alopecia Areata (AA), along with to evaluate the economic impact of the patients that may be from changing in their quality of life. There are patients with severe AA who may have little or no improvement from the treatment by diphenylcyclopropenone (DPCP) or topical steroid with minoxidil but instead having positive response from the treatment with Janus kinase(JAK) inhibitor such as Tofacitinib or Ruxolitinib. For the best of my knowledge, there was no previous study in using Tofacitinib to treat severe AA before in Thailand.

Condition or disease	Intervention/treatment	Phase
Alopecia Areata	Drug: Tofacitinib	Phase 4

Detailed Description:

Alopecia areata (AA) or spot baldness, is a condition in which hair falls off from areas of the body. It often happens on the scalp, causing a few bald spots and it may result in psychological stress even though people are generally healthy. AA is believed to be an autoimmune disease progressing from a breach in the immune privilege of the hair follicles that causes hair to fall out in small patches, it may remain unnoticeable until the patches eventually connect and then become noticeable. It can develop slowly, and also recur after years between occurrences.

By standard AA treatment guideline, DPCP is the first treatment protocol and may follow with anthralin or minoxidil. This oldy but goody treatment gives a good result of 75% in spotty hair loss and 25% in total baldness. The new invention of treatment has been introduced in the past 2 years by using JAK inhibitor, an oral medicine such as Tofacitinib and Ruxolitinib. This treatment gives a good outcome so far in this short period of time, 54-81.9% of patients had over 50% increase of hair grows over the original protocol. The theory is that JAK inhibitors would inhibit interferon-gamma and interleukin-15 signal between white blood cell and hair follicle which reducing the rate of destroying hair follicles.

The investigators propose the study to assess the safety and efficacy of Tofacitinib for extensive and recalcitrant AA and to evaluate the economic impact effecting the AA patients. Tofacitinib is an expensive medicine and needed to be taken up to 6 months to finish the course to have a best outcome so it is not a popular choice of AA treatment at present time unless it can show a promising result in recalcitrant AA.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a Cohort study which all recruited volunteers will receive Tofacitinib for total of 24 weeks. The 19 volunteers are mixed male and female Thais who suffer from severe AA over 50% of the entire scalp.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata
• Actual Study Start Date: January 12, 2019
• Estimated Primary Completion Date: September 30, 2020
• Estimated Study Completion Date: September 30, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Tofacitinib; All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.

Drug: Tofacitinib; Tofacitinib is an oral medicine in Janus kinase inhibitor 3 group which has been approved by FDA in treating Rheumatoid Arthritis. It has ability to inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the cause of hair loss.; Other Name: Xeljanz

Outcome Measures

Primary Outcome Measures :

1. The area of hair loss either on the scalp or body is measured and recorded using SALT score. [ Time Frame: 48 weeks ]
   Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologist to determine percentage of scalp hair loss. SALT system divides the scalp in 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. At beginning, the area of hair loss would be measured by checking each area for hair loss and determine the bald spots combined per SALT scale then keep record as SALT base line (SALTBL).

Secondary Outcome Measures :

1. Side effect from Tofacitinib [ Time Frame: 48 weeks ]
   Patients will come back for follow up after 1st treatment at the time set by researcher (vary differently per cases), we call this measurement SALT follow up (SALTF/U). SALT score is calculated into percentage as the formula "SALTBL minus SALTF/U then divide by SALTBL and time 100"=% change from baseline. All volunteers will be evaluated by SALT score every 4 weeks after starting the treatment. All volunteers will have total of 24 weeks treatments unless the condition is improved to satisfaction before or having intolerable side effect. Follow up will be at 28th,36th and 48th week.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Thai volunteers age between 18 and 60 years old.
• Volunteers must be patients who suffer from severe AA more than 50% of the entire scalp.
• Volunteers must be patients who are able to complete the monthly treatment at least in the first 6 months.

Exclusion Criteria:

• Patients who suffer from other hair diseases such as: Telogen effluvium, Trichotillomania, Tinea capitis
• Patients who have other diseases that can have an impact on hair loss or temporary hair loss condition with in 6 months prior to the study such as: thyroid problems, liver disease, malnutrition, hearth disease, neurological disease, gastrointestinal disorders, sexually transmitted disease, cancer, psychiatric disease.
• Patients with AA who received treatment with either steroid, Anthralin or DPCP application within 1 month before the selection or patients who had oral or injection from steroid or other medication for hair loss treatment within 3 months before the selection.
• Woman with pregnancy

Contacts and Locations

Locations

Thailand

Institute of Dermatology

Bangkok, Thailand

Sponsors and Collaborators

Institute of Dermatology, Thailand

Investigators

• Principal Investigator: Chinmanat Tangjaturonrusamee, MD; Institute of Dermatology

More Information

Publications of Results:

Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010 Feb;62(2):177-88, quiz 189-90. doi: 10.1016/j.jaad.2009.10.032.

Other Publications:

Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031. Review.

Tosti A, Iorizzo M, Botta GL, Milani M. Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial. J Eur Acad Dermatol Venereol. 2006 Nov;20(10):1243-7.

Taylor CR, Hawk JL. PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology. Br J Dermatol. 1995 Dec;133(6):914-8.

Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017 Jan;76(1):22-28. doi: 10.1016/j.jaad.2016.09.007. Epub 2016 Nov 2.

Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol. 2017 Jan;76(1):29-32. doi: 10.1016/j.jaad.2016.09.006. Epub 2016 Nov 2.

Ibrahim O, Bayart CB, Hogan S, Piliang M, Bergfeld WF. Treatment of Alopecia Areata With Tofacitinib. JAMA Dermatol. 2017 Jun 1;153(6):600-602. doi: 10.1001/jamadermatol.2017.0001.

Divito SJ, Kupper TS. Inhibiting Janus kinases to treat alopecia areata. Nat Med. 2014 Sep;20(9):989-90. doi: 10.1038/nm.3685.

• Responsible Party: Chinmanat Tangjaturonrusamee, Assistant Director of Institute of Dermatology, Institute of Dermatology, Thailand
• ClinicalTrials.gov Identifier: NCT03800979
• Other Study ID Numbers: IRB/IEB 004/2562
• First Posted: January 11, 2019
• Last Update Posted: February 11, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Chinmanat Tangjaturonrusamee, Institute of Dermatology, Thailand:

Alopecia areata; Alopecia universalis; Alopecia totalis; Tofacitinib; JAK inhibitor

Additional relevant MeSH terms:

Alopecia; Alopecia Areata; Hypotrichosis; Hair Diseases; Skin Diseases; Pathological Conditions, Anatomical; Tofacitinib; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action