Ensaios clínicos de eficácia no tratamento do melasma facial em mulheres: tiamidol 0,2% e cisteamina 5% tópicos, e picnogenol 150 mg oral
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2022-06-30
Autores
Lima, Paula Basso [UNESP]
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Universidade Estadual Paulista (Unesp)
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FUNDAMENTOS: Melasma é uma hipermelanose crônica que afeta áreas fotoexpostas, especialmente de mulheres em idade fértil. Até o momento, nenhum dos tratamentos descritos têm grande eficácia ou resultados sustentados. Novas abordagens terapêuticas precisam ser exploradas. OBJETIVO: (1) Avaliar a segurança e eficácia da terapia tópica com tiamidol 0,2% versus hidroquinona 4% tópica e fotoproteção no tratamento do melasma facial em mulheres por um período de 90 dias. (2) Avaliar a segurança e eficácia do picnogenol 75 mg via oral duas vezes ao dia versus placebo, associado à combinação tripla e fotoproteção no tratamento do melasma facial em mulheres por um período de 60 dias. (3) Avaliar a segurança e eficácia da terapia tópica com cisteamina 5% versus hidroquinona 4% tópica e fotoproteção no tratamento do melasma facial em mulheres por um período de 120 dias. MÉTODOS: (1) Ensaio clínico de intervenção, randomizado, paralelo, avaliador-cego e controlado envolvendo 50 mulheres com melasma facial. Além do filtro solar com cor (FPS 60, PPD 20), as participantes foram randomizadas por simulação computacional e alocadas consecutivamente para utilizar hidroquinona 4% creme ao deitar ou uma dupla camada de tiamidol 0,2% creme duas vezes ao dia, por 90 dias. As participantes foram avaliadas no T0, T30 e T90, e o principal desfecho foi a diferença na pontuação do mMASI. Os desfechos secundários foram melhorias na qualidade de vida dos pacientes (MELASQoL), colorimetria e avaliação do GAIS. Os dados longitudinais foram analisados como intenção de tratamento e um modelo linear misto generalizado foi usado para analisar os dados longitudinais e os dropouts. (2) Ensaio clínico de intervenção, randomizado, paralelo, duplo-cego e controlado por placebo realizado com 44 mulheres portadoras de melasma facial. Pacientes foram randomizadas por simulação computacional e alocadas consecutivamente para tomar 75 mg de picnogenol ou placebo por via oral duas vezes por dia durante 60 dias. A sequência de alocação foi ocultada do avaliador e as cápsulas foram formuladas em embalagens exatamente iguais. Ambos os grupos também receberam filtro solar com cor (FPS 50, PPD 17) para uso diurno e combinação tripla tópica ao deitar. As participantes foram avaliadas no T0 e T60, o principal desfecho foi a diferença na pontuação do mMASI. Os desfechos secundários foram melhorias na qualidade de vida dos pacientes (MELASQoL), colorimetria e avaliação do GAIS. Os dados longitudinais foram analisados como intenção de tratamento e um modelo linear misto generalizado foi usado para analisar os dados longitudinais e os dropouts. (3) Ensaio clínico de intervenção, quasi-randomizado, paralelo, avaliador cego e controlado realizado em 40 mulheres com melasma facial. Pacientes foram submetidas à aplicação de curto contato de cisteamina 5% ou hidroquinona 4% por 120 dias. Ambos os grupos utilizaram filtro solar com cor (FPS 50, PPD 19). Os indivíduos foram avaliados na inclusão e após 60 e 120 dias de tratamento. O principal desfecho foi a diferença na pontuação do mMASI. Os desfechos secundários foram melhorias na qualidade de vida dos pacientes (MELASQoL), colorimetria e avaliação do GAIS. A avaliação estatística foi realizada por um avaliador cego e os dados longitudinais foram analisados como intenção de tratamento e um modelo linear misto generalizado foi usado para analisar os dados longitudinais e os dropouts. RESULTADOS: (1) Houve somente um dropout no grupo hidroquinona, não relacionado a efeitos adversos. A idade média dos participantes foi de 43 anos, e 86% eram fototipos III–IV. Ambos os grupos apresentaram redução nos escores de mMASI, MELASQoL e contraste de cor após 90 dias (p<0,01). A redução média [intervalo de confiança de 95% (IC 95%)] dos escores mMASI foi de 43% (35-50%) para tiamidol e 33% (23-42%) para hidroquinona. Não houve diferença entre os grupos nas reduções nos escores mMASI, MELASQoL, contraste colorimétrico e GAIS (p ≥ 0,09). A análise GAIS resultou em uma melhora de 84% (IC: 95% 67–97%) para os participantes do grupo tiamidol e 74% (IC: 95% 61–93%) para aqueles do grupo hidroquinona. Houve apenas efeitos adversos leves no grupo tiamidol, dermatite alérgica de contato foi evidenciada em dois (8%) participantes. (2) Todos os participantes completaram o estudo. A idade média dos participantes foi de 39 anos, e 91% eram fototipos III–IV. Ambos os grupos apresentaram redução nos escores mMASI, MELASQoL e contraste de cor após 60 dias(p<0,01). As reduções médias (IC 95%) dos escores mMASI foram de 49% (36–61%) para o grupo picnogenol e 34% (16–47%) para o grupo placebo. As reduções nos escores mMASI e contraste colorimétrico foram superiores para o grupo picnogenol (p<0,05). A análise do GAIS resultou em uma melhora de 86% (IC 95%: 68–96%) para os participantes do grupo picnogenol e 55% (IC 95%: 32–73%) para aqueles do grupo placebo, com diferença significante entre os grupos. Não foram identificados efeitos adversos relacionados ao tratamento oral. (3) Houve somente um dropout no grupo cisteamina, não relacionado a efeitos adversos. O mMASI reduziu progressivamente ao longo do estudo em ambos os grupos, apesar do grupo HQ apresentar uma despigmentação mais rápida. A redução média dos escores mMASI foi de 24% para CYS e 41% para hidroquinona (P = 0,015) em 60 dias, e 38% para CYS e 53% para hidroquinona (P = 0,017) em 120 dias. A avaliação fotográfica revelou até 74% de melhora para ambos os grupos, sem diferença entre eles (P = 0,087). O escore MELASQoL mostrou uma diminuição progressiva para ambos os grupos ao longo do tempo, apesar da maior redução para hidroquinona após 120 dias (P = 0,018). A avaliação colorimétrica revelou despigmentação progressiva em ambos os grupos, sem diferença entre eles (P > 0,160). Nenhum efeito adverso grave foi identificado em nenhum dos grupos. Eritema e queimação foram os efeitos adversos locais mais importantes com cisteamina, embora sua frequência não tenha diferido entre os grupos (P > 0,170). CONCLUSÃO: (1) A melhora do melasma obtida com o tiamidol a 0,2% não diferiu do creme de hidroquinona a 4%. O tiamidol pode ser considerado uma opção adequada para pacientes com melasma com baixa tolerabilidade ou falha do tratamento com hidroquinona. (2) Picnogenol 75 mg duas vezes ao dia é bem tolerado e aumenta a eficácia do filtro solar de amplo espectro e da combinação tripla no tratamento do melasma facial em mulheres. (3) A cisteamina mostrou-se segura, bem tolerada e eficaz, apesar de seu desempenho inferior à hidroquinona na diminuição do mMASI e MELASQoL no tratamento do melasma.
BACKGROUND: Melasma is a chronic hypermelanosis that affects sun-exposed areas, especially in women of childbearing age. To date, none of the treatments described have great efficacy or sustained results. New therapeutic approaches need to be explored. OBJECTIVES: (1) This study compared the efficacy and tolerability of topical 0.2% thiamidol vs. 4% hydroquinone for facial melasma. (2) To compare the efficacy, safety and tolerability of 75 mg pycnogenol taken orally BID vs. a placebo, in association with the triple combination and broad-spectrum sunscreen for the treatment of facial melasma. (3) To assess the efficacy and safety of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women. METHODS: (1) Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomized by computer simulation and allocated consecutively, then they were assigned to apply a double layer of 0.2% thiamidol BID or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Severity Index (mMASI) score. Secondary outcomes were improvements in the patients’ quality of life [Melasma Quality of Life Index (MELASQoL)], colorimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation. Longitudinal data were analyzed as intention to treat and a generalized mixed linear model was used to analyze them and the dropouts. (2) A randomized, double-blind, parallel, placebo-controlled study was conducted on 44 women with facial melasma in a single centre from May 2019 through November 2019. Patients with melasma were randomized by computer simulation and allocated consecutively, then they were assigned to orally take 75 mg pycnogenol (PYC) or a placebo (PLAC) BID for 60 days. .The allocation sequence was blinded from the evaluator and the capsules were formulated in exactly the same packaging. Both groups also received tinted sunscreen [Sun Protection Factor (SPF) 50; Persistent Pigment Darkening (PPD) 17] for daytime use and a topical triple combination at bedtime. The primary outcome was a change from the baseline Modified Melasma Area Severity Index (mMASI) score. Secondary outcomes were improvements in the patients’ quality of life (MELASQoL), colorimetric indices and Global Aesthetic Improvement Scale (GAIS). Longitudinal data were analyzed as intention to treat and a generalized mixed linear model was used to analyze them and the dropouts. (3) A quasi-randomized, multicenter, evaluator-blinded clinical trial was conducted on 40 women with facial melasma, who were submitted to the nightly application of 5% cysteamine (CYS) or 4% hydroquinone (HQ) on hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were assessed at the inclusion and after 60 and 120 days of treatment for mMASI, MELASQoL, and the difference in colorimetric luminosity between melasma and the adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in the appearance of the skin through standardized photographs. Statistical evaluation was performed by a blinded evaluator and the longitudinal data were analyzed as intention to treat and a generalized mixed linear model was used to them and the dropouts. RESULTS: (1) One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III–IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35–50%) for thiamidol and 33% (23–42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colorimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67–97%) for participants in the thiamidol group and 74% (CI: 95% 61–93%) for those in the hydroquinone group. There were only mild adverse effects in the thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. (2) All participants completed the trial. The mean (SD) age of the participants was 39 (7) years, and 91% were phototypes III–IV. Both groups exhibited a reduction in mMASI scores, MELASQoL scores and colour contrast (P < 0.01). The mean (CI 95%) reductions of the mMASI scores were 49% (36–61%) for PYC and 34% (16–47%) for PLAC. The reductions in mMASI scores and colorimetric contrast were superior for the PYC group (P < 0.05). The analysis of GAIS resulted in an improvement of 86% (CI 95%: 68–96%) for the participants in the PYC group and 55% (CI 95%: 32–73%) for those in the PLAC group, with a significant difference between the groups. There were no adverse effects related to oral treatment. (3) There was only one dropout in the cysteamine group, unrelated to adverse effects. The mMASI scores progressively reduced over time for both groups, despite the HQ group perceiving faster depigmentation. The mean reduction of the mMASI scores was 24% for CYS and 41% for hydroquinone (P = 0.015) at 60 days, and 38% for CYS and 53% for hydroquinone (P = 0.017) at 120 days. The photographic evaluation revealed up to 74% improvement for both groups, without difference between them (P = 0.087). The MELASQoL score showed a progressive decrease for both groups over time, despite the greater reduction for hydroquinone after 120 days (P = 0.018). Colorimetric assessment disclosed progressive depigmenting in both groups, without difference between them (P > 0.160). No severe adverse effects were identified in either group. Erythema and burning were the most important local adverse effects with cysteamine, although their frequency did not differ between groups (P > 0.170). CONCLUSION: (1) The melasma improvement using 0.2% thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone. (2) Pycnogenol is well-tolerated and increases the effectiveness of broad-spectrum sunscreen and the triple combination in the treatment of facial melasma in women. (3) Cysteamine proved to be safe, well-tolerated, and effective, despite its inferior performance to hydroquinone in decreasing mMASI and MELASQoL in the treatment of melasma.
BACKGROUND: Melasma is a chronic hypermelanosis that affects sun-exposed areas, especially in women of childbearing age. To date, none of the treatments described have great efficacy or sustained results. New therapeutic approaches need to be explored. OBJECTIVES: (1) This study compared the efficacy and tolerability of topical 0.2% thiamidol vs. 4% hydroquinone for facial melasma. (2) To compare the efficacy, safety and tolerability of 75 mg pycnogenol taken orally BID vs. a placebo, in association with the triple combination and broad-spectrum sunscreen for the treatment of facial melasma. (3) To assess the efficacy and safety of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women. METHODS: (1) Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomized by computer simulation and allocated consecutively, then they were assigned to apply a double layer of 0.2% thiamidol BID or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Severity Index (mMASI) score. Secondary outcomes were improvements in the patients’ quality of life [Melasma Quality of Life Index (MELASQoL)], colorimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation. Longitudinal data were analyzed as intention to treat and a generalized mixed linear model was used to analyze them and the dropouts. (2) A randomized, double-blind, parallel, placebo-controlled study was conducted on 44 women with facial melasma in a single centre from May 2019 through November 2019. Patients with melasma were randomized by computer simulation and allocated consecutively, then they were assigned to orally take 75 mg pycnogenol (PYC) or a placebo (PLAC) BID for 60 days. .The allocation sequence was blinded from the evaluator and the capsules were formulated in exactly the same packaging. Both groups also received tinted sunscreen [Sun Protection Factor (SPF) 50; Persistent Pigment Darkening (PPD) 17] for daytime use and a topical triple combination at bedtime. The primary outcome was a change from the baseline Modified Melasma Area Severity Index (mMASI) score. Secondary outcomes were improvements in the patients’ quality of life (MELASQoL), colorimetric indices and Global Aesthetic Improvement Scale (GAIS). Longitudinal data were analyzed as intention to treat and a generalized mixed linear model was used to analyze them and the dropouts. (3) A quasi-randomized, multicenter, evaluator-blinded clinical trial was conducted on 40 women with facial melasma, who were submitted to the nightly application of 5% cysteamine (CYS) or 4% hydroquinone (HQ) on hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were assessed at the inclusion and after 60 and 120 days of treatment for mMASI, MELASQoL, and the difference in colorimetric luminosity between melasma and the adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in the appearance of the skin through standardized photographs. Statistical evaluation was performed by a blinded evaluator and the longitudinal data were analyzed as intention to treat and a generalized mixed linear model was used to them and the dropouts. RESULTS: (1) One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III–IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35–50%) for thiamidol and 33% (23–42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colorimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67–97%) for participants in the thiamidol group and 74% (CI: 95% 61–93%) for those in the hydroquinone group. There were only mild adverse effects in the thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. (2) All participants completed the trial. The mean (SD) age of the participants was 39 (7) years, and 91% were phototypes III–IV. Both groups exhibited a reduction in mMASI scores, MELASQoL scores and colour contrast (P < 0.01). The mean (CI 95%) reductions of the mMASI scores were 49% (36–61%) for PYC and 34% (16–47%) for PLAC. The reductions in mMASI scores and colorimetric contrast were superior for the PYC group (P < 0.05). The analysis of GAIS resulted in an improvement of 86% (CI 95%: 68–96%) for the participants in the PYC group and 55% (CI 95%: 32–73%) for those in the PLAC group, with a significant difference between the groups. There were no adverse effects related to oral treatment. (3) There was only one dropout in the cysteamine group, unrelated to adverse effects. The mMASI scores progressively reduced over time for both groups, despite the HQ group perceiving faster depigmentation. The mean reduction of the mMASI scores was 24% for CYS and 41% for hydroquinone (P = 0.015) at 60 days, and 38% for CYS and 53% for hydroquinone (P = 0.017) at 120 days. The photographic evaluation revealed up to 74% improvement for both groups, without difference between them (P = 0.087). The MELASQoL score showed a progressive decrease for both groups over time, despite the greater reduction for hydroquinone after 120 days (P = 0.018). Colorimetric assessment disclosed progressive depigmenting in both groups, without difference between them (P > 0.160). No severe adverse effects were identified in either group. Erythema and burning were the most important local adverse effects with cysteamine, although their frequency did not differ between groups (P > 0.170). CONCLUSION: (1) The melasma improvement using 0.2% thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone. (2) Pycnogenol is well-tolerated and increases the effectiveness of broad-spectrum sunscreen and the triple combination in the treatment of facial melasma in women. (3) Cysteamine proved to be safe, well-tolerated, and effective, despite its inferior performance to hydroquinone in decreasing mMASI and MELASQoL in the treatment of melasma.
Descrição
Palavras-chave
Melasma, Picnogenol, Tiamidol, Cisteamina, Melanócito, Radiação ultravioleta , Pycnogenol, Thiamidol, Cysteamine, Melanocyte, Ultraviolet radiation