Efficacy and Safety of add-on Apremilast Versus add-on Methotrexate in Patients With Oral Lichen Planus

NCT06260904 | Completed Phase 4

• 1 other identifier: AIIMS BBSR/PGThesis/23-24/112
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Lichen planus is an inflammatory disorder of unknown aetiology affecting the stratified squamous epithelia, with an estimated global prevalence of 0.22 to 0.5 %. Oral mucosa (Oral Lichen Planus; OLP) is the most commonly affected region. Corticosteroids are the primary treatment of choice. A prolonged treatment with steroids is required for clinical improvement, which increases the chances of long-term adverse effects. So, there is a need for newer, effective treatment modalities, such as retinoids, methotrexate, Janus kinase inhibitors, PDE4 inhibitors, etc. Of these, methotrexate is a dihydrofolate reductase inhibitor that inhibits the replication and function of T and B lymphocytes. It has shown a good response to OLP (around 83%) in a study by Lajevardi et al. and can be considered a treatment option in patients with moderate to severe OLP. Apremilast is a drug with a novel immunomodulatory mechanism of action. It inhibits phosphodiesterase type IV, which increases levels of cyclic adenosine monophosphate (cAMP), thus activating protein kinase A and inhibiting various inflammatory mediators. Based on a pilot study by Paul et al., apremilast is associated with clinical improvement in lichen planus. Among the various treatment options, there is a lack of head-on trials. Methotrexate is an immunosuppressant with various systemic adverse effects and requires close monitoring. Whereas apremilast is a non-immunosuppressive drug with a better safety profile, it does not show such adverse effects. These drugs can be used as an add-on to low-dose steroids in view of reducing the adverse effects associated with steroid therapy. To the best of our knowledge, there is no randomized controlled trial comparing these two drugs to date. Hence, the present study has been planned to evaluate the safety and efficacy of methotrexate versus apremilast as an add-on to the standard steroid therapy in OLP patients.

Conditions

Oral Lichen Planus

Keywords

Lichen planus; Oral lichen planus; Prednisolone; Methotrexate; Apremilast; IL 6; VAS; PGA

Outcome Measures

Primary Outcomes (1)

• Pain by Visual Analogue Scale (VAS) score

  Change in Visual Analogue Scale (VAS) score after treatment with prednisolone and methotraxate Vs Prednisolone and Apremilast at baseline, 8 weeks and 12 weeks. The VAS consists of a 10 cm line, with two endpoints representing 0 ('no pain') and 10 ('pain as bad as it could possibly be') interpretation of the scores: 0 =No Pain 2 = Mild 4 = Nagging 6 =Miserable 8 =Intense 10 = Worst

  8 weeks and 12 weeks

Secondary Outcomes (5)

• Severity by Physician global assessment of disease (PGA) score

  8 weeks and 12 weeks

• Severity and pain by oral mucosal disease severity score

  8 weeks and 12 weeks

• serum IL 6 level

  12 weeks

• Quality of life by using oral health-related quality of life score (ORAL HEALTH IMPACT PROFILE - 14 )

  8 weeks and 12 weeks

• Incidence of treatment-emergent adverse events of both test and control group

  12 weeks

Study Arms (2)

Prednisolone and Methotrexate (Control Arm)

ACTIVE COMPARATOR

prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Methotrexate 15 mg weekly for 12 weeks.

Drug: Prednisolone; Drug: Methotrexate

Prednisolone and Apremilast (Test Arm)

EXPERIMENTAL

prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Apremilast 30 mg twice daily for 12 weeks.

Drug: Prednisolone; Drug: Apremilast

Interventions

Prednisolone DRUG

prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) orally

Prednisolone and Apremilast (Test Arm); Prednisolone and Methotrexate (Control Arm)

Apremilast DRUG

Apremilast 30 mg twice daily orally

Prednisolone and Apremilast (Test Arm)

Methotrexate DRUG

Methotrexate 15 mg weekly orally

Prednisolone and Methotrexate (Control Arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 of either sex with the clinical diagnosis of oral lichen planus.
• Patients with a PGA score of ≥3 (moderate and severe oral LP).
• Patient not responding to topical or intralesional corticosteroid.
• Patients who are willing to give informed written consent.

You may not qualify if:

• Treatment with a systemic corticosteroid within the last 4 weeks.
• Patients on any immunosuppressive agents such as azathioprine, cyclosporine and others within one month of recruitment.
• Patients with clinical history and any lesion distribution suspicious of a lichenoid drug eruption and patients with other skin diseases.
• Past or current history of any malignancy including moderate to severe dysplasia of the oral mucosa on oral biopsy.
• Severe active infection, including active tuberculosis, hepatitis B or C infection
• Patients with cytopenia (Hb \<9g/dl, leukocyte count \<4000/mm3, platelet count \<100,000/mm3)
• Patient with history of alcohol abuse.
• Decreased liver or renal function (creatinine \> 2.0mg/dl, total bilirubin \> 2.5 mg/dl).
• Severe acute infection, uncontrolled diabetes mellitus, untreated glaucoma, congenital or acquired immunodeficiency, active gastroduodenal ulcer, severe osteoporosis, severe cardiac disease (NYHA grade IV), MI in the last four weeks, severe schizophrenia or depression.
• Patient with a history of hypersensitivity to Methotrexate or Apremilast.
• Pregnancy and lactation, women of childbearing age without effective contraception.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

AIIMS Bhubaneswar

Bhubaneswar, Odisha, 751019, India

Location

Related Publications (10)

• Gorouhi F, Davari P, Fazel N. Cutaneous and mucosal lichen planus: a comprehensive review of clinical subtypes, risk factors, diagnosis, and prognosis. ScientificWorldJournal. 2014 Jan 30;2014:742826. doi: 10.1155/2014/742826. eCollection 2014.

  PMID: 24672362 BACKGROUND

• Farhi D, Dupin N. Pathophysiology, etiologic factors, and clinical management of oral lichen planus, part I: facts and controversies. Clin Dermatol. 2010 Jan-Feb;28(1):100-8. doi: 10.1016/j.clindermatol.2009.03.004.

  PMID: 20082959 BACKGROUND

• Solimani F, Forchhammer S, Schloegl A, Ghoreschi K, Meier K. Lichen planus - a clinical guide. J Dtsch Dermatol Ges. 2021 Jun;19(6):864-882. doi: 10.1111/ddg.14565. Epub 2021 Jun 7.

  PMID: 34096678 BACKGROUND

• Veneri F, Bardellini E, Amadori F, Conti G, Majorana A. Efficacy of ozonized water for the treatment of erosive oral lichen planus: a randomized controlled study. Med Oral Patol Oral Cir Bucal. 2020 Sep 1;25(5):e675-e682. doi: 10.4317/medoral.23693.

  PMID: 32683383 BACKGROUND

• Le Cleach L, Chosidow O. Clinical practice. Lichen planus. N Engl J Med. 2012 Feb 23;366(8):723-32. doi: 10.1056/NEJMcp1103641. No abstract available.

  PMID: 22356325 BACKGROUND

• Mohan RPS, Gupta A, Kamarthi N, Malik S, Goel S, Gupta S. Incidence of Oral Lichen Planus in Perimenopausal Women: A Cross-sectional Study in Western Uttar Pradesh Population. J Midlife Health. 2017 Apr-Jun;8(2):70-74. doi: 10.4103/jmh.JMH_34_17.

  PMID: 28706407 BACKGROUND

• Kanwar AJ, De D. Methotrexate for treatment of lichen planus: old drug, new indication. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):e410-3. doi: 10.1111/j.1468-3083.2012.04654.x. Epub 2012 Jul 24.

  PMID: 22827806 BACKGROUND

• Lajevardi V, Ghodsi SZ, Hallaji Z, Shafiei Z, Aghazadeh N, Akbari Z. Treatment of erosive oral lichen planus with methotrexate. J Dtsch Dermatol Ges. 2016 Mar;14(3):286-93. doi: 10.1111/ddg.12636.

  PMID: 26972194 BACKGROUND

• Chauhan P, De D, Handa S, Narang T, Saikia UN. A prospective observational study to compare efficacy of topical triamcinolone acetonide 0.1% oral paste, oral methotrexate, and a combination of topical triamcinolone acetonide 0.1% and oral methotrexate in moderate to severe oral lichen planus. Dermatol Ther. 2018 Jan;31(1). doi: 10.1111/dth.12563. Epub 2017 Nov 10.

  PMID: 29124831 BACKGROUND

• Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, Hu C, Stevens RM, Day RM, Gordon KB, Korman NJ, Griffiths CE. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015 Jul;73(1):37-49. doi: 10.1016/j.jaad.2015.03.049.

  PMID: 26089047 BACKGROUND

MeSH Terms

Conditions

Lichen Planus, Oral; Lichen Planus

Interventions

Prednisolone; apremilast; Methotrexate

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Lichenoid Eruptions; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Debasish Hota, MD, DM

  Professor

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor

Model Details: randomized, add-on, active-controlled, open-label, parallel-design clinical trial

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 15, 2024
• Study Start: January 26, 2024
• Primary Completion: October 30, 2025
• Study Completion: October 30, 2025
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)