Efficacy and Safety of add-on Apremilast Versus add-on Methotrexate in Patients With Oral Lichen Planus: A Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Pain by Visual Analogue Scale (VAS) score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Prednisolone and Apremilast (Test Arm)
prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Apremilast 30 mg twice daily for 12 weeks.
干预措施: Prednisolone (Drug)
Prednisolone and Methotrexate (Control Arm)
prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Methotrexate 15 mg weekly for 12 weeks.
干预措施: Prednisolone (Drug)
Prednisolone and Methotrexate (Control Arm)
prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Methotrexate 15 mg weekly for 12 weeks.
干预措施: Methotrexate (Drug)
Prednisolone and Apremilast (Test Arm)
prednisolone 0.75mg/kg/day (a maximum dose of 30mg at baseline) and Apremilast 30 mg twice daily for 12 weeks.
干预措施: Apremilast (Drug)
结局指标
主要结局
Pain by Visual Analogue Scale (VAS) score
时间窗: 8 weeks and 12 weeks
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
次要结局
- 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)
研究者
Dr. Monalisa Jena, M.D.
Additional Professor
All India Institute of Medical Sciences, Bhubaneswar