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

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.

Timeline

Start

2024-01-26

Primary completion

2025-10-30

Completion

2025-10-30

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

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