Review question
Are corticosteroids effective and safe for the treatment of oral lichen planus that is causing pain?
Background
Oral lichen planus is a common condition that can cause long-term, painful areas on the lining of the mouth. Usual treatment is with drugs known as corticosteroids applied directly to the painful areas (topically), or taken internally (systemically). Treatment aims to reduce pain and improve healing of the mouth, but there is no cure for the disease.
Study characteristics
The evidence in this review is up-to-date as of 25 February 2019. We included 35 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 1474 participants, which tested several different corticosteroids, mostly delivered topically (on the skin). Corticosteroids were compared with one of the following: a placebo (a treatment that resembled the corticosteroid but had no active ingredient); a medicine from a category called calcineurin inhibitors; another medicine type; another corticosteroid or mode of delivery; the same corticosteroid plus an extra treatment; or an alternative treatment. Treatments were given for between one week and six months, with side effects measured throughout the treatment, and pain and healing measured at the end of treatment.
Key results
Results from two studies showed that topical corticosteroids (e.g. clobetasol propionate, flucinonide, betamethasone and triamcinolone acetonide), when applied to the mouth in a sticky cream, may be effective in reducing and stopping pain. We do not have the evidence that topical corticosteroids can eliminate the oral lichen planus lesions, and we are uncertain about side effects.
We found no consistent evidence that any particular corticosteroid was better than any other.
Three studies using another topical medicine called tacrolimus (a calcineurin inhibitor) found that this medicine may be more effective than corticosteroids, but may be more likely to cause mild side effects.
Available evidence comparing corticosteroids with other treatments is very limited.
Reliability of the evidence
The reliability of most of the evidence is very low, so we cannot be sure about the findings and future research may lead us to different conclusions.
Conclusion
The available evidence suggests that topical corticosteroids may be effective for treating painful oral lichen planus, but our confidence in these findings is limited as there were only a small number of studies and participants. There is some evidence that tacrolimus may be more effective than a corticosteroid, but evidence on negative side effects is inconclusive.
Corticosteroids have been first line for the treatment of OLP. This review found that these drugs, delivered topically as adhesive gels or similar preparations, may be more effective than placebo for reducing the pain of symptomatic OLP; however, with the small number of studies and participants, our confidence in the reliability of this finding is low. The results for clinical response were inconclusive, and we are uncertain about adverse effects. Very low-certainty evidence suggests that calcineurin inhibitors, specifically tacrolimus, may be more effective at resolving pain than corticosteroids, although there is some uncertainty about adverse effects and clinical response to tacrolimus showed conflicting results.
Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease, which can cause significant pain, particularly in its erosive or ulcerative forms. As pain is the indication for treatment of OLP, pain resolution is the primary outcome for this review. This review is an update of a version last published in 2011, but focuses on the evidence for corticosteroid treatment only. A second review considering non-corticosteroid treatments is in progress.
To assess the effects and safety of corticosteroids, in any formulation, for treating people with symptoms of oral lichen planus.
Cochrane Oral Health's Information Specialist searched the following databases to 25 February 2019: Cochrane Oral Health's Trials Register, CENTRAL (2019, Issue 1), MEDLINE Ovid, and Embase Ovid. ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. There were no restrictions on language or date of publication.
We considered randomised controlled clinical trials (RCTs) of any local or systemic corticosteroid treatment compared with a placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug, or the same corticosteroid plus an adjunctive treatment.
Three review authors independently scanned the titles and abstracts of all reports identified, and assessed risk of bias using the Cochrane tool and extracted data from included studies. For dichotomous outcomes, we expressed the estimates of effects of an intervention as risk ratios (RR), with 95% confidence intervals (CI). For continuous outcomes, we used mean differences (MD) and 95% CI. The statistical unit of analysis was the participant. We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE.
We included 35 studies (1474 participants) in this review. We assessed seven studies at low risk of bias overall, 11 at unclear and the remaining 17 studies at high risk of bias. We present results for our main outcomes, pain and clinical resolution measured at the end of the treatment course (between one week and six months), and adverse effects. The limited evidence available for comparisons between different corticosteroids, and corticosteroids versus alternative or adjunctive treatments is presented in the full review.
Corticosteroids versus placebo
Three studies evaluated the effectiveness and safety of topical corticosteroids in an adhesive base compared to placebo. We were able to combine two studies in meta-analyses, one evaluating clobetasol propionate and the other flucinonide. We found low-certainty evidence that pain may be more likely to be resolved when using a topical corticosteroid rather than a placebo (RR 1.91, 95% CI 1.08 to 3.36; 2 studies, 72 participants; I² = 0%). The results for clinical effect of treatment and adverse effects were inconclusive (clinical resolution: RR 6.00, 95% CI 0.76 to 47.58; 2 studies, 72 participants; I² = 0%; very low-certainty evidence; adverse effects RR 1.48, 95% 0.48 to 4.56; 3 studies, 88 participants, I² = 0%, very low-certainty evidence).
Corticosteroids versus calcineurin inhibitors
Three studies compared topical clobetasol propionate versus topical tacrolimus. We found very low-certainty evidence regarding any difference between tacrolimus and clobetasol for the outcomes pain resolution (RR 0.45, 95% CI 0.24 to 0.88; 2 studies, 100 participants; I² = 80%), clinical resolution (RR 0.61, 95% CI 0.38 to 0.99; 2 studies, 52 participants; I² = 95%) and adverse effects (RR 0.05, 95% CI 0.00 to 0.83; 2 studies, 100 participants; very low-certainty evidence) .
One study (39 participants) compared topical clobetasol and ciclosporin, and provided only very low-certainty evidence regarding the rate of clinical resolution with clobetasol (RR 3.16, 95% CI 1.00 to 9.93), pain resolution (RR 2.11, 95% CI 0.76 to 5.86) and adverse effects (RR 6.32, 95% CI 0.84 to 47.69).
Two studies (60 participants) that compared triamcinolone and tacrolimus found uncertain evidence regarding the rate of clinical resolution (RR 0.86, 95% CI 0.55 to 1.35; very low-certainty evidence) and that there may be a lower rate of adverse effects in the triamcinolone group (RR 0.47, 95% CI 0.22 to 0.99; low-certainty evidence). These studies did not report on pain resolution.