Topical Calcineurin Inhibitors in the Treatment of Oral Lichen Planus

A Systematic Review and Meta-analysis

S.-L. Sun; J.-J. Liu; B. Zhong; J.-K. Wang; X. Jin; H. Xu; F.-Y. Yin; T.-N. Liu; Q.-M. Chen; X. Zeng

Disclosures

The British Journal of Dermatology. 2019;181(6):1166-1176. 

In This Article

Abstract and Introduction

Abstract

Background: TCS (topical corticosteroids) are the first-line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, pimecrolimus and ciclosporin for OLP is still controversial.

Objectives: To compare the efficacy and safety of TCI vs. TCS for OLP.

Methods: The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events.

Results: Twenty-one trials involving 965 patients were included in the analysis. For the treatment of OLP (3–8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus–TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short-term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious.

Conclusions: The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short-term treatment in recalcitrant OLP. Further well-designed trials are warranted to evaluate the long-term efficacy and safety of TCI.

Introduction

Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disorder, which has a prevalence of 0·5–3%. Owing to its potential for malignancy, OLP was included in the Oral Potential Malignant Disorders.[1] As OLP affects patients' quality of life, drugs are needed with few adverse events to improve signs and symptoms and reduce relapse rates. The main topical drugs for OLP are topical corticosteroids (TCS). Because some patients are not responsive to TCS or are at risk of adverse events, other effective and safe drugs are required. In recent years, calcineurin inhibitors, including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune-mediated diseases, such as atopic dermatitis, graft-versus-host disease and contact allergy.[2–6] Calcineurin inhibitors inhibit the transcription and production of many proinflammatory cytokines by binding to cytoplasmic proteins of T cells (tacrolimus and pimecrolimus bind to FK506-binding protein, and ciclosporin binds to cyclophilin).[7,8]

However, there are still some controversies about whether topical calcineurin inhibitors (TCI) can be used as alternatives to TCS for patients with OLP. So far, there has been no meta-analysis on all the three TCI (tacrolimus, pimecrolimus and ciclosporin) vs. TCS for OLP. We conducted a systematic review and meta-analysis of these three TCI vs. TCS to evaluate their short-term efficacy and safety in OLP. The aim of this paper was to provide clinicians with more treatment options and to increase the remission rate of OLP.

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