Topical calcineurin inhibitors in the treatment of oral lichen planus: a systematic review and meta‐analysis

Abstract

Summary 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. What's already known about this topic? The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS). Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs. Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune‐mediated diseases. What does this study add? TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short‐term treatment of OLP. The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious. The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short‐term and long‐term efficacy and safety of TCI compared with TCS.

Efficacy of ozonized water for the treatment of erosive oral lichen planus: a randomized controlled study

“…previously demonstrated on mouse models, T cell–specific activation of Nrf2-regulated antioxidant response appears to help in the maintenance of a low proinflammatory environment and optimal T cell function that subsequently results in reduced oxidative and inflammatory tissue injury ( 27 ). A limited 3-month follow-up was chosen for the purpose of this study, as it is considered to be reasonable both to intercept the most recurrent forms of OLP and to limit the other confounding factors that may be associated with long-term follow-up ( 28 ). However, such a short follow-up might not fully describe OLP clinical course.…”

Lichen planus – a clinical guide

“…Another approach and off‐label is the topical application (twice daily for up to 8 weeks) of pimecrolimus or tacrolimus, two calcineurin inhibitors [94]. Yet, in this setting case reports of a possible carcinogenic effect have been published (squamous cell carcinoma, oropharyngeal carcinoma and melanoma) [95–97].…”

Lichen planus – ein Klinikleitfaden

“…Ein weiterer Ansatz, jedoch off‐label , ist die topische Therapie mit den Calcineurin‐Inhibitoren Pimecrolimus oder Tacrolimus (zweimal täglich für bis zu acht Wochen) [94]. Bei mukosaler Anwendung existieren Fallberichte über eine mögliche karzinogene Wirkung (Plattenepithelkarzinom, Oropharynxkarzinom und Melanom) [95–97].…”