There is no evidence for difference in efficacy between tacrolimus and pimecrolimus.
Local adverse effects, e.g. transient burning or stinging associated with application, are probably more common with topical tacrolimus than with topical corticosteroids.
| Reference | Study type | Population | Intervention and comparison | Outcome | Risk of bias «Additional comments for included studies...»2 |
|---|---|---|---|---|---|
| «McCaughey C, Machan M, Bennett R, ym. Pimecrolimus...»1 | RCT | Patients with erosive OLP, n=21 | Topical pimecrolimus 1% cream and placebo (vehicle) | Primary: IGA (incl. spontaneous pain on VAS) | Moderate |
| «Sun SL, Liu JJ, Zhong B, ym. Topical calcineurin i...»2 | SR and MA | Patients with OLP, 9/21 studies, 463/965 patients assessed tacrolimus or pimecrolimus | Topical tacrolimus or pimecrolimus and topical corticosteroid | (i) improvement of clinical signs including signs improved and changes in clinical score, (ii) improvement of clinical symptoms, (changes in pain score VAS), (iii) relapse | Most had low /unclear |
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»3 | SR and MA | Patients with OLP, 35 studies, n=1474 | Any local or systemic corticosteroid treatment and placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug or the same corticosteroid plus an adjunctive treatment | Primary: Pain resolution 1) pain score 2) pain resolution |
Low (7 studies) Unclear (11 studies) High (17 studies) |
| «Su Z, Hu J, Cheng B, ym. Efficacy and safety of to...»4 | SR and MA | Patients with OLP, 9 studies, n=335 | Topical clobetasol, triamcinolone, pimecrolimus or isotretinoin and topical tacrolimus (0.03/0.1%) | Primary: Clinical response (score and resolution of the disease). Secondary outcomes included pain (score (VAS) and resolution) |
Low (5 studies) unclear (4 studies) |
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»5 | SR and NMA | Patients with OLP, 34 studies, n=1284 | Topical corticosteroids or topical calcineurin inhibitors compared with each other or placebo at any drug concentration and treatment duration | Primary: Clinical response rate* Secondary: (1) symptom-reducing effect, defined as the mean change in the pain score based on VAS, (2) sign-reducing effect, defined as the mean change in the lesion score based on the scale suggested by Thongprasom et al.**, relapse | In all RCTs, most domains had a low and some concerns of risk of bias |
IGA=Investigator's global assessment; NMA=network meta-analysis; MA=meta-analysis; OLP=oral lichen planus, RCT=randomized controlled trial; SR=systematic review; VAS=visual analogue scale
*Proportion of patients with sign and/or symptom improvement (including complete and partial responses) at the end of treatment.
**Thongprasom K, Luangjarmekorn L, Sererat T, & Taweesap W. Relative efficacy of fluocinolone acetonide compared with triamcinolone acetonide in treatment of oral lichen planus. J Oral Pathol Med 1992; 21(10), 456–458.
| Reference | Comments |
|---|---|
| «McCaughey C, Machan M, Bennett R, ym. Pimecrolimus...»1 | Study included patients 18 years or older, who had biopsy-confirmed diagnosis of erosive
OLP. Subjects were excluded if they were pregnant, had received systemic immunosuppressants,
oral retinoids, or any other systemic therapies known or suspected to have an effect
on OLP within 4 weeks prior to participation in the study. The primary outcome was
Investigator's Global Assessment (IGA) of the overall severity of the disease, which
included erythema, measurement of the size of any target erosion in millimeters, and
assessment of spontaneous pain (VAS 1-10). Change in the mean IGA at week 6 was significant
in intervention group but not in control (placebo) group. Two patients in the pimecrolimus
cream treatment group withdrew from the study prematurely, at week 4 and at week 6. Pimecrolimus levels were detected in 9/10 of the pimecrolimus-treated pts. These levels were consistently low (day 7). Statistically significant differences in other laboratory values were not detected between pimecrolimus and placebo treated subjects. The pimecrolimus cream was well-tolerated. No clinically relevant, drug-related adverse events were reported. |
| «Sun SL, Liu JJ, Zhong B, ym. Topical calcineurin i...»2 | Included were RCTs that met the following criteria: (i) patients with symptomatic or asymptomatic OLP diagnosed according to clinical features, histopathology and/or direct immunofluorescence; (ii) TCI (tacrolimus, pimecrolimus and ciclosporin) compared with TCS, with all of them in topical or gargle preparations; and (iii) at least one of the predefined outcomes on efficacy and safety available. 2 studies reported blood levels of tacrolimus, they were usually undetectable (1 patient had a minimally increased level). |
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»3 | Included were 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). |
| «Su Z, Hu J, Cheng B, ym. Efficacy and safety of to...»4 | Included were original longitudinal studies on the topical administration of tacrolimus in symptomatic, clinically and histologically diagnosed oral lichen planus patients. At least one of the predefined outcomes on efficacy, safety, and stability had to be available. |
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»5 | Included were 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. |
TCI=topical calcineurin inhibitor; TCS=topical corticosteroid
| Reference | Number of studies and number of patients (I/C) | Follow-up time | I | C | Event rate (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision. |
|||||
| «McCaughey C, Machan M, Bennett R, ym. Pimecrolimus...»1 | 1 study, n=21 (pimecrolimus n=10/vehicle n=11) | 6 weeks + 6 weeks open label phase (pimecrolimus) | Pain score decrease 1.5 P=0.03 |
Pain score decrease 0.9 P=0.21 |
|
| «Sun SL, Liu JJ, Zhong B, ym. Topical calcineurin i...»2 | 6 studies (3 tacrolimus n=188, 3 pimecrolimus n=98/ topical corticosteroid) 3 studies, n=98 (pimecrolimus/topical corticosteroid) |
3–4 weeks (or 1 month) 3–4 weeks (or 1 month) 8 weeks (or 2 months) |
tacrolimus–TCS: SMD 0.39, (-0.07–0.84) pimecrolimus–TCS: SMD 0.35, (-0.05–0.75) 0.25 (95% CI -0.15-0.65) |
||
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»3 | 1 study, n= 68 (topical clobetasol/tacrolimus) 2 studies, n=70 (topical triamcinolone/pimecrolimus) |
3 weeks 2 months |
MD 0.08, (-0.33 - 0.49) p=0.7 MD -0.05 (-2.97 - 2.87) p=.097 |
||
| «Su Z, Hu J, Cheng B, ym. Efficacy and safety of to...»4 | 1 study, n= 30 (tacrolimus/pimecrolimus) | 8 weeks | MD −0.04; (−1.07 - 0.99) | ||
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»5 | 8 RCTs, n=403 with 3 direct pairwise comparisons. 4 studies, n=134 (pimecrolimus/triamcinolone) 2 studies, n=120 (tacrolimus/triamcinolone) |
2-4 weeks 8 weeks 2-4 weeks |
SMD 0.38 (0.04 - 0.73) SMD 0.75 (-0.16 - 1.66) SMD 0.41 (0.05 - 0.77) |
||
I=intervention; C=comparison; CI=confidence interval; TCS=topical corticosteroid; MD=mean difference; SMD=standardized mean difference; RCT=randomized controlled trial
| 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. *The most common adverse effect was transient burning or stinging associated with application. Others included dyspepsia, skin rash, local swelling, gastrointestinal upset. |
|||||
| «McCaughey C, Machan M, Bennett R, ym. Pimecrolimus...»1 | 1 RCT, n=21 (pimecrolimus/placebo) | 6 weeks, + 6 weeks open label phase (pimecrolimus) | No clinically relevant, drug-related adverse events were reported | ||
| «Sun SL, Liu JJ, Zhong B, ym. Topical calcineurin i...»2 | 7 studies, n=340 (tacrolimus/topical corticosteroids) | RR 2.05 (1.27-3.33) | |||
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»3 | 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...»3 | 2 RCTs, n=58 (triamcinolone/tacrolimus) | 3-8 | 243 per 1000 (114-511) | 516 per 1000 | RR 0.47 (0.22-0.99) |
| «Lodi G, Manfredi M, Mercadante V, ym. Intervention...»3 | 1 RCT, n=35 (triamcinolone/pimecrolimus) | RR 0.21 (0.01-4.1) | |||
| «Su Z, Hu J, Cheng B, ym. Efficacy and safety of to...»4 | 5 studies, n=198 (tacrolimus/corticosteroids) 1 study, n=20 (tacrolimus/ placebo) |
3-8 3 |
RR 2.63 (1.40-4.95) RR 2.18 (0.81-5.89) |
||
| «Yuan P, Qiu X, Ye L, ym. Efficacy of topical admin...»5 | 23 RCTs, n=887 (15 direct pairwise comparisons among 9 interventions) 1) Placebo/tacrolimus 2) Betamethasone/tacrolimus 3) Clobetasol/tacrolimus 4) Dexamethasone/tacrolimus 5) Fluocinolone/tacrolimus 6) Tacrolimus/triamcinolone |
2-12 | 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) OR 0.20 (0.07,0.61) 2) OR 0.28 (0.05,1.59) 3) OR 0.96 (0.34,2.75) 4) OR 0.07 (0.01,0.36) 5) OR 1.90 (0.30,11.83) 6) OR 6.49 (2.39,17.61) |
||
RCT=randomized controlled trial; I= intervention; C=comparison; CI=confidence interval; RR= risk ratio; NMA=network meta-analysis; DEX=dexamethasone; TRI=triamcinolone; PBO=placebo; BEM=betamethasone; PIM=pimecrolimus; TAC=tacrolimus; CSA=ciclosporin; CLO=clobetasol; FLU=fluocinolone