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

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.

Study Overview

• Status: Completed
• Conditions: Alopecia Areata
• Intervention / Treatment: Drug: Tofacitinib

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand
    • Institute of Dermatology

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Xeljanz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Responders vs Non-Responders Using SALT Score	The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 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. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects From Tofacitinib	Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.	48 weeks

Collaborators and Investigators

• Sponsor: Institute of Dermatology, Thailand
• Investigators: Principal Investigator: Chinmanat Lekhavat, MD, Institute of Dermatology

Publications and helpful links

General 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.
• 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. doi: 10.1111/j.1468-3083.2006.01781.x.
• 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. doi: 10.1111/j.1365-2133.1995.tb06925.x.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2019
• Primary Completion (Actual): January 30, 2021
• Study Completion (Actual): January 30, 2021

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (Actual): January 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: JAK inhibitor; Tofacitinib; Alopecia areata; Alopecia universalis; Alopecia totalis
• Additional Relevant MeSH Terms: Skin Diseases; Pathological Conditions, Anatomical; Hypotrichosis; Hair Diseases; Alopecia; Alopecia Areata; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: IRB/IEB 004/2562

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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