Effectiveness and Safety of Tofacitinib in Patients With Recalcitrant Frontal Fibrosing Alopecia : A Pilot Study

Frontal Fibrosing Alopecia Clinical Trial

— Tofacitinib  

Official title:

Effectiveness and Safety of Tofacitinib in Patients With Recalcitrant Frontal Fibrosing Alopecia : A Pilot Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06202560
• Other study ID #: IRB/IEC 022/2566
• Status: Enrolling by invitation
• Phase: N/A
• Start date: November 29, 2023
• Est. completion date: May 15, 2024

Study information

• Verified date: January 2024
• Source: Institute of Dermatology, Thailand
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to study the efficacy and safety of Tofacitinib therapy in Thai patients with recalcitrant frontal fibrosing alopecia.

The main questions are

1. Does Tofacitinib significantly reduce Frontal Fibrosing Alopecia Severity Index (FFASI), Frontal Fibrosing Alopecia Severity Score (FFASS), Lichen planopillaris Activity Index (LPPAI) compared to baseline and after 16 weeks?

2. Is Tofacitinib significantly different for adverse events compared to baseline and after 16 weeks? Participants will have a check-up in clinical and investigation and then get prescribed oral Tofacitinib 5 mg twice a day for 12 weeks. After that, they will have follow-up every 4 weeks until week 16.

Description:

1.The researcher collects personal data including age, gender, weight, height, body mass index, waist circumference, personal medical history, history of medication use in the past 3 months (menstruation history for female subjects), as well as records of symptoms such as hair loss history and diagnosis, pattern of hair loss on the scalp or other areas, comorbidities, family history, and other accompanying symptoms.

2.The researchers require the patients to undergo various blood tests before receiving treatment.

3. The researchers collect data on the patients' skin conditions using Digital Camera and a Dermoscope. They capture images of the scalp, eyebrows, eyelashes, facial rashes, joint folds, arms, legs, nails, mouth, and dark spots (if present).

4.Participants in the research will receive oral Tofacitinib medication with a dosage of 5 mg, twice a day, for 12 weeks. They will be scheduled to come for follow-up every 4 weeks throughout the 12-week period, and will continue to be followed up for 4 weeks after stopping the medication. The total duration of the research will be 16 weeks. The purpose is to evaluate the effectiveness and safety of the medication.

1. The symptoms of the disease to be assessed include facial papule, LP pigmentosus, pruritus, trichodynia, perifollicular erythema, and perifollicular hyperkeratosis.

2. Frontal Fibrosing Alopecia Severity Index (FFASI)

3. Frontal Fibrosing Alopecia Severity Score (FFASS)

4. Lichen Planopillaris Activity Index (LPPAI)

5. The photograph will be taken. The areas photographed include the scalp, eyebrows, eyelashes, facial rashes, joint folds, arms, legs, nails, dark spots (if present), and mouth. Two expert physicians will evaluate the photographs independently, and the photographs of 10 patients were assessed to determine the consistency among the physicians before evaluating the actual patients. The evaluation will determine whether the patient's conditions have improved, remained stable, or worsened.

6. Dermoscopy will be performed. The areas examined include the scalp, eyebrows, eyelashes, facial rashes, joint folds, arms, legs, nails, dark spots (if present), and mouth.

7. The patient's abnormal symptoms after medication administration will be evaluated, including respiratory tract infections, skin abnormalities, gastrointestinal abnormalities, urinary tract infections, or other symptoms.

8. Laboratory tests will be conducted to assess the safety of the medication at weeks 4, 12, and 16.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 11
• Est. completion date: May 15, 2024
• Est. primary completion date: April 5, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Thai males or females who were at least 18 years old

2. Participants who were diagnosed with frontal fibrosing alopecia The criteria for the diagnosis of frontal fibrosis alopecia are 2 major criteria or 1 major criterion plus 2 minor criteria. (Vañó-Galván et al., 2014)

3. Participants who were diagnosed with recalcitrant frontal fibrosing alopecia

• The patient who fails treatment of at least one drug, such as hydroxychloroquine, and/or receives others, such as immunosuppressive drugs, pioglitazone, and retinoids. However, the symptoms of FFA still appear, such as perifollicular erythematous and/or scale, after taking treatment for more than 3 months

• The patient continued taking the medicine as prescribed and coming to follow-up

• The patient still has the medical record, such as a picture and dermoscopy

• The patient does not need a washout time from the current medicine

Exclusion Criteria:

1. Patients who were diagnosed with a disease that may relate to hair growth within six months, such as thyroid disease, iron deficiency anemia, liver disease, heart disease, neurological system disease, gastroenteritis disease, sexual disease, cancer, and psychologic disease

2. Pregnancy

3. Patients who have contraindications to take oral Tofacitinib such as severe infection, allergy to Tofacitinib, venous thromboembolism, leukopenia, severe liver disease, severe kidney failure, pneumonia, cancer

4. Patients who received strong or moderate to strong CYP3A4 agents

5. Patients who had positive on HBsAg and/or HCV

Related Conditions & MeSH terms

• Alopecia
• Alopecia Areata
• Frontal Fibrosing Alopecia
• Lichen Planopilaris
• Lichen Planus

Intervention

Drug:
• Tofacitinib 5 MG
Participants in the research will receive oral Tofacitinib medication with a dosage of 5 mg, twice a day, for 12 weeks. They will be scheduled to come for follow-up every 4 weeks throughout the 12-week period, and will continue to be followed up for 4 weeks after stopping the medication. The total duration of the research will be 16 weeks. The purpose is to evaluate the effectiveness and safety of the medication.

Locations

Country	Name	City	State
Thailand	Hair and Nail center, Institute of Dermatology	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Dermatology, Thailand

Country where clinical trial is conducted

Thailand, 

References & Publications (28)

Alves de Medeiros AK, Speeckaert R, Desmet E, Van Gele M, De Schepper S, Lambert J. JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases. PLoS One. 2016 Oct 6;11(10):e0164080. doi: 10.1371/journal.pone.0164080. eCollection 2016. — View Citation

Autrup H, Thurlow BJ, Warwick GP. The effects of the continuous administration of N,N-dimethyl-4-phenylazoaniline (DAB) on the activities and the inducibilities of some drug-metabolizing enzymes in rat liver. Chem Biol Interact. 1975 Nov;11(5):313-28. doi: 10.1016/0009-2797(75)90001-0. — View Citation

Banka N, Mubki T, Bunagan MJ, McElwee K, Shapiro J. Frontal fibrosing alopecia: a retrospective clinical review of 62 patients with treatment outcome and long-term follow-up. Int J Dermatol. 2014 Nov;53(11):1324-30. doi: 10.1111/ijd.12479. Epub 2014 Apr 16. — View Citation

Binnion PF, Das Gupta R. Prophylactic antiarrhythmic drug therapy in acute myocardial infarction. Cardiovasc Clin. 1975;7(2):203-17. No abstract available. — View Citation

Chern CJ, Beutler E. Biochemical and electrophoretic studies of erythrocyte pyridoxine kinase in white and black Americans. Am J Hum Genet. 1976 Jan;28(1):9-17. — View Citation

Childs JM, Sperling LC. Histopathology of scarring and nonscarring hair loss. Dermatol Clin. 2013 Jan;31(1):43-56. doi: 10.1016/j.det.2012.08.001. Epub 2012 Sep 26. — View Citation

Craiglow BG, King BA. Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy. JAMA Dermatol. 2015 Oct;151(10):1110-2. doi: 10.1001/jamadermatol.2015.1520. — View Citation

Ehrhart IC, Parker PE, Weidner WJ, Dabney JM, Scott JB, Haddy FJ. Coronary vascular and myocardial responses to carotid body stimulation in the dog. Am J Physiol. 1975 Sep;229(3):754-60. doi: 10.1152/ajplegacy.1975.229.3.754. — View Citation

Gupta AK, Daigle D, Abramovits W, Vincent KD. XELJANZ (Tofacitinib) for Chronic Plaque Psoriasis. Skinmed. 2015 May-Jun;13(3):227-9. No abstract available. — View Citation

Harries MJ, Meyer K, Chaudhry I, E Kloepper J, Poblet E, Griffiths CE, Paus R. Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche. J Pathol. 2013 Oct;231(2):236-47. doi: 10.1002/path.4233. — View Citation

Hashmi AA, Rashid K, Ali R, Dowlah TU, Ali AH, Diwan MA, Malik UA, Irfan M, Zia S, Ahmad A. Clinicopathological Features of Alopecia With an Emphasis on Etiology and Histopathological Characteristics of Scarring Alopecia. Cureus. 2022 Aug 3;14(8):e27661. doi: 10.7759/cureus.27661. eCollection 2022 Aug. — View Citation

Ho A, Shapiro J. Medical therapy for frontal fibrosing alopecia: A review and clinical approach. J Am Acad Dermatol. 2019 Aug;81(2):568-580. doi: 10.1016/j.jaad.2019.03.079. Epub 2019 Apr 3. — View Citation

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. — View Citation

Kerkemeyer KLS, Eisman S, Bhoyrul B, Pinczewski J, Sinclair RD. Frontal fibrosing alopecia. Clin Dermatol. 2021 Mar-Apr;39(2):183-193. doi: 10.1016/j.clindermatol.2020.10.007. Epub 2020 Oct 17. — View Citation

Kossard S. Postmenopausal frontal fibrosing alopecia. Scarring alopecia in a pattern distribution. Arch Dermatol. 1994 Jun;130(6):770-4. Erratum In: Arch Dermatol 1994 Nov;130(11):1407. — View Citation

Litaiem N, Idoudi S. Frontal Fibrosing Alopecia. 2023 Aug 7. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK519001/ — View Citation

Liu LY, King BA. Tofacitinib for the Treatment of Severe Alopecia Areata in Adults and Adolescents. J Investig Dermatol Symp Proc. 2018 Jan;19(1):S18-S20. doi: 10.1016/j.jisp.2017.10.003. — View Citation

MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: a review of 60 cases. J Am Acad Dermatol. 2012 Nov;67(5):955-61. doi: 10.1016/j.jaad.2011.12.038. Epub 2012 Apr 13. — View Citation

Mamolo C, Harness J, Tan H, Menter A. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, improves patient-reported outcomes in a phase 2b, randomized, double-blind, placebo-controlled study in patients with moderate-to-severe psoriasis. J Eur Acad Dermatol Venereol. 2014 Feb;28(2):192-203. doi: 10.1111/jdv.12081. Epub 2013 Jan 7. — View Citation

Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, Gupta P, Krishnaswami S, Tan H, Harness JA. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012 Sep;167(3):668-77. doi: 10.1111/j.1365-2133.2012.11168.x. — View Citation

Rakowska A, Gradzinska A, Olszewska M, Rudnicka L. Efficacy of Isotretinoin and Acitretin in Treatment of Frontal Fibrosing Alopecia: Retrospective Analysis of 54 Cases. J Drugs Dermatol. 2017 Oct 1;16(10):988-992. — View Citation

Sperling LC, Cowper SE. The histopathology of primary cicatricial alopecia. Semin Cutan Med Surg. 2006 Mar;25(1):41-50. doi: 10.1016/j.sder.2006.01.006. — View Citation

Szymonowicz M, Lowkis B. In vitro testing method of polymers candidate destined for contact with blood. Polim Med. 1990;20(1-4):43-55. — View Citation

To D, Beecker J. Frontal Fibrosing Alopecia: Update and Review of Challenges and Successes. J Cutan Med Surg. 2018 Mar/Apr;22(2):182-189. doi: 10.1177/1203475417736279. Epub 2017 Oct 23. — View Citation

Van Gorkom HJ, Pulles MP, Wessels JS. Light-induced changes of absorbance and electron spin resonance in small photosystem II particles. Biochim Biophys Acta. 1975 Dec 11;408(3):331-9. doi: 10.1016/0005-2728(75)90134-6. — View Citation

Vano-Galvan S, Molina-Ruiz AM, Serrano-Falcon C, Arias-Santiago S, Rodrigues-Barata AR, Garnacho-Saucedo G, Martorell-Calatayud A, Fernandez-Crehuet P, Grimalt R, Aranegui B, Grillo E, Diaz-Ley B, Salido R, Perez-Gala S, Serrano S, Moreno JC, Jaen P, Camacho FM. Frontal fibrosing alopecia: a multicenter review of 355 patients. J Am Acad Dermatol. 2014 Apr;70(4):670-678. doi: 10.1016/j.jaad.2013.12.003. Epub 2014 Feb 5. — View Citation

Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L, Singh P, Petukhova L, Mackay-Wiggan J, Christiano AM, Clynes R. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014 Sep;20(9):1043-9. doi: 10.1038/nm.3645. Epub 2014 Aug 17. — View Citation

Yang CC, Khanna T, Sallee B, Christiano AM, Bordone LA. Tofacitinib for the treatment of lichen planopilaris: A case series. Dermatol Ther. 2018 Nov;31(6):e12656. doi: 10.1111/dth.12656. Epub 2018 Sep 27. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effectiveness of oral tofacitinib in recalcitrant Frontal Fibrosing Alopecia(FFA)	The effectiveness of this study will be evaluated by comparing the Frontal Fibrosing Alopecia Severity Index (FFASI) (Max score = 100 and Min score = 0), Frontal Fibrosing Alopecia Severity Score (FFASS) (Max score = 25 and Min score = 0), and Lichen Planopilaris Activity Index (LPPAI) (Max score = 10 and Min score = 0) between week 0 (baseline week) and week 16. If a patient has a lower score on all of these indices, it means the treatment is more effective. In addition, two expert physicians will independently evaluate the photographs. The two evaluators will determine whether the patient's conditions have improved, remained stable, or worsened.	16 weeks after taking oral Tofacitinib
Secondary	Clinical & Investigation Safety of oral tofacitinib in recalcitrant (FFA)	The safety of clinical and laboratory investigation and oral Tofacitinib treatment is evident, as patients do not experience any complaints of abnormal symptoms after taking the drugs. These symptoms may include respiratory tract infections, skin abnormalities, gastrointestinal abnormalities, urinary tract infections, or other adverse events at weeks 4, 12, and 16.	16 weeks after taking oral Tofacitinib