Non-Cochrane · intervention · PM41694423
Evaluating calcineurin inhibitors as alternatives to steroids in treating Oral Lichen Planus: a systematic review and meta-analysis.
Sárai Bálint Zsombor, Gutmacher Ellay, Cavalcante Bianca Golzio Navarro, et al. · Frontiers in oral health · 2026 · PubMed · doi:10.3389/froh.2026.1755525
Findings
Population Adults with symptomatic oral lichen planus (erosive, ulcerative or atrophic)
9 findings
| Topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporin) | Topical steroids (clobetasol, betamethasone, triamcinolone) | Adverse effect: transient burning First 2 days of treatment · Pairwise random-effects meta-analysis | OR 2.45 [0.55, 10.85] 117 [-44, 452] more per 1000 High 4 studies · 247 participants |
| Topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporin) | Topical steroids (clobetasol, betamethasone, triamcinolone) | Pain severity (VAS 0-10) 4 weeks (follow-up weeks 3-4) · Pairwise random-effects meta-analysis | MD -0.06 [-0.55, 0.44] Moderate Downgraded: risk of bias 5 studies · 276 participants |
| Topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporin) | Topical steroids (clobetasol, betamethasone, triamcinolone) | Lesion morphology (Clinical Score 0-5) 4 weeks · Pairwise random-effects meta-analysis | MD -0.08 [-0.74, 0.57] Moderate Downgraded: risk of bias 3 studies · 158 participants |
| Topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporin) | Topical steroids (clobetasol, betamethasone, triamcinolone) | Pain severity (VAS 0-10) 4 weeks · Network meta-analysis (Bayesian, 95% credible interval) | MD -0.11 [-0.97, 0.62] GRADE not reported 5 studies · 275 participants |
| Topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporin) | Placebo | Pain severity (VAS 0-10) 4 weeks · Network meta-analysis (Bayesian, 95% credible interval) | MD -1.32 [-3.57, 0.96] GRADE not reported 5 studies · 275 participants |
| Topical steroids (clobetasol, betamethasone, triamcinolone) | Placebo | Pain severity (VAS 0-10) 4 weeks · Network meta-analysis (Bayesian, 95% credible interval) | MD -1.21 [-3.56, 1.22] GRADE not reported 5 studies · 275 participants |
| Topical steroids (clobetasol, betamethasone, triamcinolone) | Other treatments in the network | Pain severity (VAS 0-10) 4 weeks · Network ranking, SUCRA: ST | SUCRA 61 GRADE not reported 5 studies · 275 participants |
| Placebo | Other treatments in the network | Pain severity (VAS 0-10) 4 weeks · Network ranking, SUCRA: Placebo | SUCRA 13.74 GRADE not reported 5 studies · 275 participants |
| Topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporin) | Other treatments in the network | Pain severity (VAS 0-10) 4 weeks · Network ranking, SUCRA: CNI | SUCRA 75.27 GRADE not reported 5 studies · 275 participants |
Included primary studies 57
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Ibrahim 2023 matched by author and year (probable) | NR | 1 other review | not stated | not extracted yet |
| Malik 2021 matched by author and year (probable) | NR | 1 other review | not stated | not extracted yet |
| Seth 2022 matched by author and year (probable) | NR | 1 other review | not stated | not extracted yet |
| Arduino 2014 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Arduino 2014 Pimecrolimus vs. tacrolimus for the topical treatment of unresponsive oral erosive lichen planus: a 8 week randomized double-blind… PMID:23451852 | 2014 | this review only | not stated | not extracted yet |
| Arduino 2018 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Arduino 2018 Randomized, placebo-controlled, double-blind trial of clobetasol propionate 0.05% in the treatment of oral lichen planus. PMID:29297958 | 2018 | this review only | not stated | not extracted yet |
| Arunkumar 2015 matched by author and year (probable) | NR | this review only | Pain severity (VAS 0-10); Lesion morphology (Clinical Score 0-5) | not extracted yet |
| Arunkumar 2015 Relative efficacy of pimecrolimus cream and triamcinolone acetonide paste in the treatment of symptomatic oral lichen planus. PMID:25767355 | 2015 | this review only | Pain severity (VAS 0-10); Lesion morphology (Clinical Score 0-5) | not extracted yet |
| Azizi 2007 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Azizi 2007 The comparison of efficacy of adcortyl ointment and topical tacrolimus in treatment of erosive oral lichen planus. PMID:23277842 | 2007 | this review only | not stated | not extracted yet |
| Corrocher 2008 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Corrocher 2008 Comparative effect of tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus. PMID:18269664 | 2008 | this review only | not stated | not extracted yet |
| Ezzatt 2019 matched by author and year (probable) | NR | this review only | Adverse effect: transient burning | not extracted yet |
| Ezzatt 2019 Topical pimecrolimus versus betamethasone for oral lichen planus: a randomized clinical trial. PMID:29909565 | 2019 | this review only | Adverse effect: transient burning | not extracted yet |
| Georgaki 2022 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Georgaki 2022 A randomized clinical trial of topical dexamethasone vs. cyclosporine treatment for oral lichen planus. PMID:34564686 | 2022 | this review only | not stated | not extracted yet |
| Gorouhi 2007 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Gorouhi 2007 Randomized trial of pimecrolimus cream versus triamcinolone acetonide paste in the treatment of oral lichen planus. PMID:17658663 | 2007 | this review only | not stated | not extracted yet |
| Hettiarachchi 2017 matched by author and year (probable) | NR | this review only | Pain severity (VAS 0-10); Lesion morphology (Clinical Score 0-5) | not extracted yet |
| Hettiarachchi 2017 Comparison of topical tacrolimus and clobetasol in the management of symptomatic oral lichen planus: A double-blinded, randomized clinical… PMID:27633647 | 2017 | this review only | Pain severity (VAS 0-10); Lesion morphology (Clinical Score 0-5) | not extracted yet |
| Ibrahim 2023 Evaluation of muco-adhesive tacrolimus patch on caspase-3 induced apoptosis in oral lichen planus: a randomized clinical trial. PMID:36788511 | 2023 | this review only | not stated | not extracted yet |
| Kaur 2016 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Kavlakova 2022 matched by author and year (probable) | NR | this review only | Pain severity (VAS 0-10) | not extracted yet |
| Kavlakova 2022 Evaluation of clinical efficacy of topical tacrolimus 0.1% and clobetasol propionate 0.05% in desquamative gingivitis, manifestation of… PMID:35856102 | 2022 | this review only | Pain severity (VAS 0-10) | not extracted yet |
| Laeijendecker 2006 matched by author and year (probable) | NR | this review only | Adverse effect: transient burning | not extracted yet |
| Laeijendecker 2006 A comparison of treatment of oral lichen planus with topical tacrolimus and triamcinolone acetonide ointment. PMID:16710580 | 2006 | this review only | Adverse effect: transient burning | not extracted yet |
| Malik 2012 Treatment of symptomatic oral lichen planus (OLP) with 0.1% tacrolimus powder in Oraguard-B - A pilot prospective study. PMID:23960543 | 2012 | this review only | not stated | not extracted yet |
| Malik 2021 Topical Tacrolimus vs Topical Triamcinolone equally effective in the Treatment of Oral Lichen Planus DOI:10.53350/pjmhs211571500 | 2021 | this review only | not stated | not extracted yet |
| McCaughey 2011 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| McCaughey 2011 Pimecrolimus 1% cream for oral erosive lichen planus: a 6-week randomized, double-blind, vehicle-controlled study with a 6-week open-label… PMID:21175873 | 2011 | this review only | not stated | not extracted yet |
| Passeron 2007 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Passeron 2007 Treatment of oral erosive lichen planus with 1% pimecrolimus cream: a double-blind, randomized, prospective trial with measurement of… PMID:17438179 | 2007 | this review only | not stated | not extracted yet |
| Radfar 2008 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Radfar 2008 A comparative treatment study of topical tacrolimus and clobetasol in oral lichen planus. PMID:18230389 | 2008 | this review only | not stated | not extracted yet |
| Revanappa 2012 Evaluation of Efficacy of Tacrolimus 0.1% in Orabase and Triamcinolone Acetonide 0.1% in Orabase in the Management of Symptomatic Oral… DOI:10.5005/jp-journals-10011-1311 | 2012 | this review only | Lesion morphology (Clinical Score 0-5) | not extracted yet |
| Revanappa 2012 matched by author and year (probable) | NR | this review only | Lesion morphology (Clinical Score 0-5) | not extracted yet |
| Rodstrom 1994 Erosive oral lichen planus treated with clobetasol propionate and triamcinolone acetonide in Orabase: A double-blind clinical trial DOI:10.3109/09546639409081837 | 1994 | this review only | not stated | not extracted yet |
| Rodstrom 1994 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Schroeder 2024 matched by author and year (probable) | NR | this review only | Pain severity (VAS 0-10) | not extracted yet |
| Schroeder 2024 Topical tacrolimus orabase versus topical clobetasol propionate orabase in the treatment of symptomatic oral lichen planus: a pilot… PMID:39348002 | 2024 | this review only | Pain severity (VAS 0-10) | not extracted yet |
| Seth 2022 Comparative Evaluation of the Efficacy of Topical Amlexanox 5%, Triamcinolone Acetonide 0.1%, and Tacrolimus 0.03% in the Treatment of… DOI:10.4103/jiaomr.jiaomr_16_21 | 2022 | this review only | not stated | not extracted yet |
| Siponen 2016 Topical tacrolimus, triamcinolone acetonide, and placebo in oral lichen planus: a pilot randomized controlled trial. PMID:28168769 | 2017 | this review only | not stated | not extracted yet |
| Siponen 2017 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Sivaraman 2016 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Sivaraman 2016 A randomized triple-blind clinical trial to compare the effectiveness of topical triamcinolone acetonate (0.1%), clobetasol propionate… PMID:27829754 | 2016 | this review only | not stated | not extracted yet |
| Sonthalia 2012 matched by author and year (probable) | NR | this review only | Adverse effect: transient burning | not extracted yet |
| Sonthalia 2012 Comparative efficacy of tacrolimus 0.1% ointment and clobetasol propionate 0.05% ointment in oral lichen planus: a randomized double-blind… PMID:23067089 | 2012 | this review only | Adverse effect: transient burning | not extracted yet |
| Swift 2005 matched by author and year (probable) | NR | this review only | Pain severity (VAS 0-10) | not extracted yet |
| Swift 2005 The effectiveness of 1% pimecrolimus cream in the treatment of oral erosive lichen planus. PMID:15857105 | 2005 | this review only | Pain severity (VAS 0-10) | not extracted yet |
| Vohra 2015 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Volz 2008 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Volz 2008 Pimecrolimus cream 1% in erosive oral lichen planus--a prospective randomized double-blind vehicle-controlled study. PMID:18647310 | 2008 | this review only | not stated | not extracted yet |
| Voute 1993 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Voûte 1993 Fluocinonide in an adhesive base for treatment of oral lichen planus. A double-blind, placebo-controlled clinical study. PMID:8426717 | 1993 | this review only | not stated | not extracted yet |
| Yoke 2006 matched by author and year (probable) | NR | this review only | Pain severity (VAS 0-10); Adverse effect: transient burning | not extracted yet |
| Yoke 2006 A randomized controlled trial to compare steroid with cyclosporine for the topical treatment of oral lichen planus. PMID:16831672 | 2006 | this review only | Pain severity (VAS 0-10); Adverse effect: transient burning | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults (18 years or older) with histopathologically and clinically proven symptomatic oral lichen planus (erosive, ulcerative, atrophic) | Adults with oral lichen planus (28 RCTs in qualitative synthesis; 486 patients in 10 RCTs in quantitative synthesis) |
| Intervention | Topical calcineurin inhibitors | Topical tacrolimus 0.03% to 0.1%, pimecrolimus 0.5% to 1%, cyclosporin (n=11 RCTs in meta-analysis) |
| Comparison | Topical steroids or placebo | Topical steroids (clobetasol, betamethasone, triamcinolone, dexamethasone) and placebo (one three-arm trial) |
| Outcomes | Severity of pain, lesion morphology, adverse effects | Pain VAS (5 studies), Clinical Score for lesion morphology (3 studies), transient burning (4 studies) |
| Study designs | Randomized controlled trials, English language | RCTs; pairwise random-effects and Bayesian network meta-analysis; treatment periods 1 to 12 weeks |
| Timing | Not specified | Follow-up grouped to weeks 1-2 and 3-4; main analyses at 4 weeks; transient burning in first 2 days |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Yes | Partial Yes | no |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |