Clinical trial NCT06260904: Efficacy and Safety of add-on Apremilast Versus add-on Methotrexate in Patients With Oral Lichen Planus
Official title: Efficacy and Safety of add-on Apremilast Versus add-on Methotrexate in Patients With Oral Lichen Planus: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Oral Lichen Planus
Keywords: Lichen planus
Oral lichen planus
Prednisolone
Methotrexate
Apremilast
IL 6
VAS
PGA
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2024-02-15
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, add-on, active-controlled, open-label, parallel-design clinical trial
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Pain by Visual Analogue Scale (VAS) score
timeFrame: 8 weeks and 12 weeks
Secondary outcomes:
measure: Severity by Physician global assessment of disease (PGA) score
timeFrame: 8 weeks and 12 weeks
measure: Severity and pain by oral mucosal disease severity score
timeFrame: 8 weeks and 12 weeks
measure: serum IL 6 level
timeFrame: 12 weeks
measure: Quality of life by using oral health-related quality of life score (ORAL HEALTH IMPACT PROFILE - 14 )
timeFrame: 8 weeks and 12 weeks
measure: Incidence of treatment-emergent adverse events of both test and control group
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bhubaneswar
country: India
facility: AIIMS Bhubaneswar
state: Odisha
Study officials:
affiliation: Professor
name: Debasish Hota, MD, DM
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.