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Intervensi untuk actinic keratoses

Background

Actinic keratoses are a skin disease caused by long‐term sun exposure, and their lesions have the potential to develop into squamous cell carcinoma. Treatments for actinic keratoses are sought for cosmetic reasons, for the relief of associated symptoms, or for the prevention of skin cancer development. Detectable lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present. The interventions available for the treatment of actinic keratoses include individual lesion‐based (e.g. cryotherapy) or field‐directed (e.g. topical) treatments. These might vary in terms of efficacy, safety, and cosmetic outcomes.

Objectives

To assess the effects of topical, oral, mechanical, and chemical interventions for actinic keratosis.

Search methods

We searched the following databases up to March 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also searched trials registers, conference proceedings, and grey literature sources.

Selection criteria

Randomised controlled trials (RCTs) comparing the treatment of actinic keratoses with either placebo, vehicle, or another active therapy.

Data collection and analysis

At least two authors independently abstracted data, which included adverse events, and assessed the quality of evidence. We performed meta‐analysis to calculate a weighted treatment effect across trials, and we expressed the results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes (e.g. participant complete clearance rates), and mean difference (MD) and 95% CI for continuous outcomes (e.g. mean reduction in lesion counts).

Main results

We included 83 RCTs in this review, with a total of 10,036 participants. The RCTs covered 18 topical treatments, 1 oral treatment, 2 mechanical interventions, and 3 chemical interventions, including photodynamic therapy (PDT). Most of the studies lacked descriptions of some methodological details, such as the generation of the randomisation sequence or allocation concealment, and half of the studies had a high risk of reporting bias. Study comparison was difficult because of the multiple parameters used to report efficacy and safety outcomes, as well as statistical limitations. We found no data on the possible reduction of squamous cell carcinoma.

The primary outcome 'participant complete clearance' significantly favoured four field‐directed treatments compared to vehicle or placebo: 3% diclofenac in 2.5% hyaluronic acid (RR 2.46, 95% CI 1.66 to 3.66; 3 studies with 420 participants), 0.5% 5‐fluorouracil (RR 8.86, 95% CI: 3.67 to 21.44; 3 studies with 522 participants), 5% imiquimod (RR 7.70, 95% CI 4.63 to 12.79; 9 studies with1871 participants), and 0.025% to 0.05% ingenol mebutate (RR 4.50, 95% CI 2.61 to 7.74; 2 studies with 456 participants).

It also significantly favoured the treatment of individual lesions with photodynamic therapy (PDT) compared to placebo‐PDT with the following photosensitisers: aminolevulinic acid (ALA) (blue light: RR 6.22, 95% CI 2.88 to 13.43; 1 study with 243 participants, aminolevulinic acid (ALA) (red light: RR 5.94, 95% CI 3.35 to 10.54; 3 studies with 422 participants), and methyl aminolevulinate (MAL) (red light: RR 4.46, 95% CI 3.17 to 6.28; 5 studies with 482 participants). ALA‐PDT was also significantly favoured compared to cryotherapy (RR 1.31, 95% CI 1.05 to 1.64).

The corresponding comparative risks in terms of number of participants completely cleared per 1000 were as follows: 313 with 3% diclofenac compared to 127 with 2.5% hyaluronic acid; 136 with 0.5% 5‐fluorouracil compared to 15 with placebo; 371 with 5% imiquimod compared to 48 with placebo; 331 with ingenol mebutate compared to 73 with vehicle; 527 to 656 with ALA/MAL‐PDT treatment compared to 89 to 147 for placebo‐PDT; and 580 with ALA‐PDT compared to 443 with cryotherapy.

5% 5‐fluorouracil efficacy was not compared to placebo, but it was comparable to 5% imiquimod (RR 1.85, 95% Cl 0.41 to 8.33).

A significant number of participants withdrew because of adverse events with 144 participants affected out of 1000 taking 3% diclofenac in 2.5% hyaluronic acid, compared to 40 participants affected out of 1000 taking 2.5% hyaluronic acid alone, and 56 participants affected out of 1000 taking 5% imiquimod compared to 21 participants affected out of 1000 taking placebo.

Based on investigator and participant evaluation, imiquimod treatment and photodynamic therapy resulted in better cosmetic outcomes than cryotherapy and 5‐fluorouracil.

Authors' conclusions

For individual lesions, photodynamic therapy appears more effective and has a better cosmetic outcome than cryotherapy. For field‐directed treatments, diclofenac, 5‐fluorouracil, imiquimod, and ingenol mebutate had similar efficacy, but their associated adverse events and cosmetic outcomes are different. More direct comparisons between these treatments are needed to determine the best therapeutic approach.

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Intervensi untuk actinic keratoses

Actinic keratoses adalah sejenis penyakit kulit yang disebabkan oleh pendedahan kepada cahaya matahari untuk jangka masa yang panjang. Kulit yang rosak menunjukkan bintik‐bintik kecil, merah, kasar dan leper yang dipanggil actinic keratoses atau lesi (lesion), yang terasa seperti tompokan kulit kering. Tanda‐tanda seperti pendarahan dan kesakitan boleh dikaitkan dengan actinic keratoses. Selain itu, actinic keratoses berpotensi untuk menjadi kanser kulit jika tidak dirawat. Sebab‐sebab untuk rawatan termasuklah penampilan kosmetik, melegakan simptom, atau mencegah kanser kulit. Rawatan boleh diarahkan ke atas lesi‐lesi secara berasingan atau ke atas kawasan kulit yang lebih besar, di mana beberapa lesi boleh muncul samada yang boleh dilihat dan tidak boleh dilihat (rawatan arah kawasan).

Kajian sistematik ini melibatkan hasil dari 83 percubaan klinikal rawak terkawal yang menilai 24 rawatan, dengan 10,036 orang responden yang dikenalpasti dan diagnosis dengan actinic keratosis. Kami sertakan 18 krim topikal atau gel yang disapu pada kawasan kulit oleh responden: gel adapalene, aretinoid methyl sulfone (Ro 14‐9706), oleogel berasaskan betulin, calcipotriol (vitamin D), colchicine, diclofenac, 2‐(difluoromethyl)‐dl‐ornithine (DFMO), 5‐fluorouracil, ß‐1,3‐D‐glucan, imiquimod, ingenol mebutate (PEP005), isotretinoin, masoprocol, nicotinamide, resiquimod, pelindung matahari, DL‐α‐tocopherol (vitamin E), dan tretinoin. Salah satu rawatan, etretinate, telah diambil secara oral. Kakitangan klinikal memberi dua rawatan mekanikal (karbon dioksida dan laser pelapisan baru Er:YAG) pada kawasan kulit, dan mereka juga memberi tiga rawatan kimia: cryotherapy (rawatan pembekuan) ke atas lesi‐lesi secara berasingan atau pada satu kawasan kulit, dan pengelupasan menggunakan asid trichloroacetic pada kawasan kulit.

Kesan‐kesan klinikal hasil daripada rawatan actinic keratoses dilaporkan berbeza antara satu kajian dengan kajian lain. Walaupun terdapat percanggahan, ia dapat disimpulkan bahawa terdapat beberapa pilihan rawatan yang baik untuk actinic keratoses. Actinic keratoses berjaya dirawat dengan rawatan cryotherapy, diclofenac, 5‐fluorouracil, imiquimod, ingenol mebutate, terapi photodynamic, pelapisan baru, dan pengelupasan menggunakan asid trichloroacetic. Rawatan yang berbeza‐beza ini berkesan secara amnya. Kerengsaan kulit dikaitkan dengan beberapa rawatan, seperti diclofenac dan 5‐fluorouracil, tetapi kesan sampingan lain jarang berlaku. Rupa akhir secara kosmetik berbeza untuk satu rawatan dengan rawatan yang lain. Rawatan menggunakan imiquimod dan terapi photodynamic menghasilkan penampilan kosmetik yang lebih baik berbanding cryotherapy dan 5‐fluorouracil.

Rawatan dengan terapi photodynamic memberi keputusan terapeutik dan kosmetik yang lebih baik daripada cryotherapy untuk lesi‐lesi yang dirawat berasingan. Untuk rawatan arah kawasan, diclofenac, 5‐fluorouracil, imiquimod dan ingenol mebutate adalah pilihan yang baik, berkaitan dengan kesan sampingan dan keputusan kosmetik yang berbeza. Oleh itu, pilihan rawatan untuk actinic keratosis bergantung kepada bilangan lesi, keputusan yang dikehendaki oleh individu terbabit, dan toleransi kepada rawatan.