There seems to be minor differences in the effect on pain between different topical corticosteroids. Topical corticosteroids available in Finland (clobetasol, betamethasone, fluticasone, triamcinolone) are all suitable treatment options for alleviation of pain in OLP patients. The lowest adverse event rate was reported for triamcinolone and betamethasone.
The evidence is based on RCT-studies and network meta-analysis including also direct comparisons with placebo. Level of evidence is downgraded one level due to imprecision, which may be partly explained by individual response to corticosteroids or the subjective outcome (pain) measure.
| Reference | Study type | Population | Intervention and comparison | Outcome | Risk of bias «Additional comments for included studies...»2 |
|---|---|---|---|---|---|
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | SR and MA | Patients with OLP, 35 studies, n=1474. | Any local or systemic corticosteroid treatment vs. placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug or the same corticosteroid plus an adjunctive treatment | Primary: pain pain score: VAS scale 1-10, pain resolution: measured with VAS or 4-grade or 5‐grade score) |
Low (7 studies) Unclear (11 studies) High (17 studies) |
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»2 | NMA and pairwise MA |
Patients with OLP, 34 studies, n= 1284 | Topical corticosteroids or topical calcineurin inhibitor compared with each other or placebo at any drug concentration and treatment duration | Primary: clinical response rate* Secondary: (1) symptom-reducing effect (mean change in the pain score based on VAS, 0-10) (2) sign-reducing effect, (mean change in the lesion score) «Zhang Y, Mao C, Zhu J, ym. Comparing the efficacy ...»3 (3) relapse |
In all RCTs, most domains had a low and some concerns of risk of bias |
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis; NMA=network meta-analysis; OLP=oral lichen planus; VAS=visual analogue scale
*Clinical response rate was the proportion of patients with sign and/or symptom improvement (including complete and partial responses) at the end of treatment.
| Reference | Comments |
|---|---|
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | RCTs with participants satisfying the following criteria: clinical and histological
diagnosis of OLP, painful symptoms associated with OLP, not concurrently receiving
any other treatment for OLP or treatment likely to modify their OLP (e.g. systemic
steroids, antifungals or immunosuppressants). Pain resolution was the primary outcome. Pain score (VAS) between clobetasol and placebo was compared only in one study, which was also included in «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»2. |
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»2 | RCTs (without language restriction) that met the following inclusion criteria: (i) participants were clinically and/or histologically diagnosed as OLP without any other oral diseases and (ii) the interventions were topical corticosteroids or topical calcineurin inhibitor compared with each other or placebo at any drug concentration and treatment duration. Studies comparing the same corticosteroid with different modalities were excluded. |
| Reference | Number of studies and number of patients (I/C) | Follow-up time, weeks | Mean (SD) I | Mean (SD) C | Mean difference IV, Fixed (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision. |
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| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | 1 RCT, n=32 0.05% clobetasol propionate/placebo |
8 | 1.4 (1.74) | 3.2 (3.062) | -1.8 (-3.54, -0.09) |
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»2 | 16 RCTs, n=759 (11 direct pairwise comparisons among 9 interventions) 1) clobetasol vs. placebo 2) dexamethasone vs. placebo 3) betamethasone vs. placebo 4) fluticasone vs. placebo 5) placebo vs. triamcinolone |
2-8 | 1) SMD 0.62 (0.02, 1.22) 2) SMD 0.96 (0.18, 1.74) 3) SMD 0.68 (-0.17, 1.52) 4) SMD –0.54 (-1.44, 0.36) 5) SMD –0.48 (-1.15, 0.19) |
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I=intervention; C=comparison; CI=confidence interval; RCT=randomized controlled trial; SD=standard deviation, SMD=standardized mean difference
| Reference | Number of studies and number of patients (I/C) | Follow-up time, weeks | Anticipated absolute effect I | Anticipated absolute effect C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision. |
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| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | 2 RCTs, n=72 1) 0.05% clobetasol propionate/placebo 2) 0.025% fluocinonide in an adhesive cream/placebo |
8-9 | 584 per 1000 (330 to 1000) | 306 per 1000 | RR 1.91 (1.08-3.36) |
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | 2 RCTs, n=100 clobetasol/tacrolimus |
3-8 | 198 per 1000 | 440 per 1000 | RR 0.45 (0.24-0.88) |
I=intervention; C=comparison; CI=confidence interval; RCT=randomized controlled trial, RR=risk ratio
| Reference | Number of studies and number of patients (I/C) | Follow-up time, weeks | Anticipated absolute effect I | Anticipated absolute effect C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: low The quality of evidence is downgraded due to imprecision. *Adverse effects were mainly local, such as candidiasis. Some participants also reported gastrointestinal reflux. |
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| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | 3 RCTs, n= 88 1) 0.05% clobetasol propionate/placebo n=32 2) 0.025% fluocinonide in an adhesive cream/placebo) n=40 3) 0.1% triamcinolone acetonide/placebo n=16 |
3-9 | 132 per 1000 (43 to 405) | 89 per 1000 | RR 1.48 (0.48-4.56) |
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | 2 RCTs, n=100 clobetasol/tacrolimus |
3-8 | 9 per 1000(0-149 | 180 per 1000) | RR 0.05 (0.00-0.83) |
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»1 | 2 RCTs, n=58 triamcinolone/tacrolimus |
3-8 | 243 per 1000 (114-511) | 516 per 1000 | RR 0.47 (0.22-0.99) |
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»2 | 23 RCTs, n=887 (15 direct pairwise comparisons among 9 interventions) NMA comparisons to placebo 1) DEX 2) TRI 3) BEM 4) CLO 5) FLU |
P-scores for safety (lower adverse effect occurence) DEX 0.93 TRI 0.83 PBO 0.76 BEM 0.66 PIM 0.41 CLO 0.29 TAC 0.27 CSA 0.23 FLU 0.12 1) 0.37 (0.05, 2.57) 2) 1.30 (0.40, 4.16) 3) 1.42 (0.24, 8.42) 4) 4.81 (1.30, 17.86) 5) 9.48 (1.50, 60.03) |
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TAC=tacrolimus; PIM=pimecrolimus; CSA=cyclosporine; TRI=triamcinolone; BEM=betamethasone; DEX=dexamethasone; CLO=clobetasol; FLU=fluocinolone; PBO=placebo. P-scores from 0 (worst) to 1 (most effective or most safe) within the range of treatments.
I=intervention; C=comparison; CI=confidence interval; RCT=randomized controlled trial; RR=risk ratio
Comment: A recent meta-analysis «Zhang Y, Mao C, Zhu J, ym. Comparing the efficacy ...»3 shows similar results and concludes: highly effective topical corticosteroids are preferred, and immunosuppressants can be used when corticosteroids are ineffective or cause adverse effects, both in terms of pain control and sign score reduction.