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1.
J Eur Acad Dermatol Venereol ; 32(3): 403-410, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29055155

RESUMO

BACKGROUND: Palmoplantar psoriasis is a variant of psoriasis vulgaris which can severely impair quality of life. OBJECTIVES: The main objectives of this double-blind, placebo-controlled, randomized study were to assess the efficacy and impact on quality of life and work productivity of apremilast for the treatment of moderate-to-severe palmoplantar psoriasis. METHODS: A total of 100 patients with moderate-to-severe palmoplantar psoriasis were randomized to either apremilast 30 mg bid or placebo for 16 weeks. At Week 16, all patients received apremilast 30 mg bid until Week 32. The primary endpoint was the proportion of patients who achieved a Palmoplantar Psoriasis Physician Global Assessment (PPPGA) of 0/1 at Week 16. RESULTS: There was no significant difference in the proportion of patients who achieved a PPPGA of 0/1 at Week 16 between patients randomized to apremilast (14%) and placebo (4%; P = 0.1595). After 32 weeks of treatment with apremilast, 24% of patients achieved a PPGA of 0/1. In addition, apremilast was superior to placebo in achieving Palmoplantar Psoriasis Area Severity Index (PPPASI) 75 (apremilast: 22%; placebo: 8%; P = 0.0499), in improving PPPASI (apremilast: -7.4 ± 7.1; placebo: -3.6 ± 5.9; P = 0.0167), Dermatology Life Quality Index score (apremilast: -4.3 ± 5.1; placebo: -0.8 ± 4.5; P = 0.0004) and in reducing activity impairment (apremilast: -11.0 ± 22.3; placebo: 2.5 ± 25.5; P = 0.0063). CONCLUSION: Despite the absence of a significant difference between apremilast and placebo in proportion of patients achieving a PPPGA of 0/1, the presence of significant differences observed for several secondary endpoints suggests that apremilast may have a role in the treatment of moderate-to-severe palmoplantar psoriasis.


Assuntos
Dermatoses do Pé/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Inibidores da Fosfodiesterase 4/uso terapêutico , Psoríase/tratamento farmacológico , Talidomida/análogos & derivados , Método Duplo-Cego , Eficiência , Feminino , Dermatoses do Pé/fisiopatologia , Dermatoses da Mão/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Psoríase/fisiopatologia , Qualidade de Vida , Índice de Gravidade de Doença , Talidomida/uso terapêutico , Trabalho
2.
Br J Dermatol ; 176(6): 1456-1464, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28078678

RESUMO

BACKGROUND: Actinic keratosis (AK) is a common sun-related skin condition, which can progress to squamous cell carcinoma and occur in cancerized fields. OBJECTIVES: To investigate in a phase I/II trial the safety and efficacy of ingenol disoxate as topical field therapy for patients with AK on the balding scalp. METHODS: Part 1 was a phase I, open-label, dose-escalation trial investigating up to six doses of ingenol disoxate to determine the maximum tolerated dose (MTD). Part 2 was a phase II, randomized, double-blind, parallel group, vehicle-controlled trial. Patients were randomized 2 : 2 : 1 to receive ingenol disoxate 0·037%, 0·05% or vehicle gel once daily for two consecutive days. Percentage reduction in AK count from baseline, complete clearance (AKCLEAR 100) and partial clearance (≥ 75% AK count reduction; AKCLEAR 75) were assessed at week 8. RESULTS: The MTD in part 1 was 0·075% based on a dose-dependent increase in the number and severity of adverse events. Two lower doses of ingenol disoxate gel (0·037%, 0·05%) were assessed in part 2, which showed a reduction in AK count from baseline to week 8 (0·037%, 72·7%; 0·05%, 78·5% vs. vehicle 12·6; P < 0·001), and rates of AKCLEAR 100 and AKCLEAR 75 were significantly higher in active treatment groups compared with vehicle (P ≤ 0·007). Local skin responses peaked at day 3 and declined rapidly. Adverse events were generally mild to moderate in intensity, and were most commonly application site pain/pruritus. CONCLUSIONS: Ingenol disoxate 0·037% and 0·05% gel was effective and superior to vehicle, and well tolerated as field therapy for AK on the balding scalp.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Diterpenos/administração & dosagem , Ceratose Actínica/tratamento farmacológico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Administração Cutânea , Idoso , Alopecia/complicações , Fármacos Dermatológicos/efeitos adversos , Diterpenos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Géis , Humanos , Ceratose Actínica/complicações , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Dermatoses do Couro Cabeludo/complicações , Resultado do Tratamento , Adulto Jovem
3.
J Eur Acad Dermatol Venereol ; 31(1): 107-113, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27500949

RESUMO

BACKGROUND: The efficacy of ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal IgG4 antibody, was demonstrated in moderate-to-severe psoriasis patients when administered via prefilled syringe (PFS). OBJECTIVE: To evaluate the effect of two drug delivery devices on the pharmacokinetics (PK) of ixekizumab as well as efficacy and safety with both devices. METHODS: In the first 12 weeks of an open-label, phase 3 study, moderate-to-severe psoriasis patients were randomized to ixekizumab delivery via PFS or autoinjector device. Randomization was stratified by weight (<80 kg, 80-100 kg, >100 kg), injection assistance (yes/no) and injection site (arm, thigh or abdomen). Following a 160-mg initial dose at week 0, patients received subcutaneous 80-mg ixekizumab as a single injection every 2 weeks for 12 weeks. Blood samples were collected following the initial 160-mg dose on days 2, 4, 7, 10 and 14 for PK analysis. Primary PK parameters were maximum concentration (Cmax ) and area under the curve (AUC0-tlast ) where tlast is the time of last sample (14 days ± 24 h). Efficacy was assessed by percent improvement on the Psoriasis Area and Severity Index (PASI) at week 12. Adverse event reporting, vital signs and clinical laboratory data were used to evaluate safety. RESULTS: Of 204 randomized patients, 192 were included in the PK analysis (PFS: 94; autoinjector: 98). The PFS and autoinjector showed similar geometric mean Cmax (90% CI) [15.0 µg/mL (13.9-16.1) vs. 14.8 µg/mL (13.8-15.9)] and geometric mean AUC0-tlast (90% CI) [157 µg × day/mL (147-168) vs. 154 µg × day/mL (144-165)]. When comparing Cmax and AUC0-tlast of the autoinjector to PFS, the geometric LS mean ratios were 0.97. At week 12, mean percent PASI improvement (via modified baseline observation carried forward) was similar with the PFS (89.3%) and autoinjector (86.9%). Both devices had safety results that were consistent with the known safety profile of ixekizumab. CONCLUSION: The PK, efficacy and safety of ixekizumab administered subcutaneously by PFS and autoinjector were similar. Clinicaltrials.gov number: NCT01777191 https://clinicaltrials.gov/ct2/show/NCT01777191.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Injeções Subcutâneas , Índice de Gravidade de Doença
4.
Br J Dermatol ; 174(4): 770-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26663215

RESUMO

BACKGROUND: Severe acne vulgaris has limited therapeutic options. OBJECTIVES: To evaluate photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL, 80 mg g(-1) ) as the photosensitizer in severe facial acne. METHODS: A double-blind, randomized, vehicle-controlled multicentre trial in 153 patients (aged 12-35 years) with severe facial acne [Investigator's Global Assessment (IGA) score 4; 25-75 inflammatory lesions with ≤ 3 nodules; 20-100 noninflammatory lesions]. Treatment (four treatments 2 weeks apart) involved incubation with MAL (n = 100) or vehicle cream (n = 53) for 1·5 h under occlusion, then illumination (635-nm red light, total dose 37 J cm(-2) ). IGA assessment and standardized lesion counts were performed before each treatment and 12 weeks after the first treatment. Treatment success was defined as improvement from baseline in IGA by ≥ 2 grades at 12 weeks. Safety assessments were for pain (10-cm visual analogue scale, immediately after illumination), erythema (four-point rating scale) and adverse events. RESULTS: At 12 weeks, PDT using MAL 80 mg g(-1) reduced inflammatory lesions vs. vehicle PDT (mean change -15·6 vs. -7·8, P = 0·006; mean percentage change -37·3% vs. -16·2%, P = 0·003). However, noninflammatory lesions did not decrease significantly (mean change -11·8 vs. -10·7, P = 0·85; mean percentage change -28·6% vs. -24·9%, P = 0·72). Treatment success rates were greater with MAL-PDT 80 mg g(-1) (44% vs. 26%, P = 0·013). Pain was low and manageable by briefly pausing illumination. There was similar pain or erythema with successive treatments. CONCLUSIONS: PDT using topical MAL 80 mg g(-1) and red light may offer promise for severe acne vulgaris.


Assuntos
Acne Vulgar/tratamento farmacológico , Ácido Aminolevulínico/análogos & derivados , Dermatoses Faciais/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Administração Cutânea , Adolescente , Adulto , Ácido Aminolevulínico/administração & dosagem , Ácido Aminolevulínico/efeitos adversos , Criança , Método Duplo-Cego , Toxidermias/etiologia , Feminino , Humanos , Masculino , Pomadas/administração & dosagem , Dor/etiologia , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Resultado do Tratamento , Adulto Jovem
5.
J Am Coll Surg ; 189(2): 152-7, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10437836

RESUMO

BACKGROUND: The purpose of this study was to evaluate the hypothesis that awake and alert blunt trauma patients with Glasgow Coma Scores of 14 or 15 (regardless of blood ethanol level or other injuries sustained) can be effectively evaluated with clinical examination without radiographic evaluation of the cervical spine. STUDY DESIGN: During a 32-month period at an urban Level 1 Trauma Center, 2,176 consecutive blunt trauma patients who presented with Glasgow Coma Scores of 14 or 15 were prospectively evaluated by trauma resident housestaff. Housestaff performed physical examinations of the neck and questioned the patients for the presence of neck pain. Following study form documentation of the cervical neck examination, a lateral cervical spine x-ray was performed. Further studies such as swimmer's view and CAT scan were performed if the lateral x-ray could not completely evaluate C1 to C7. These further studies were considered part of the lateral cervical spine (c-spine) x-ray screen. Attending radiologists performed final x-ray interpretations. RESULTS: The study consisted of 2,176 patients, 33 (1.6%) of whom were diagnosed with cervical spine injury. Of the 33 patients with cervical spine injury, 3 had negative clinical examinations (sensitivity, 91%). Lateral c-spine x-ray screen was negative in 1 of these 3 patients. The 2 patients with negative c-spine clinical examination but positive lateral c-spine x-ray screens were diagnosed with C2 spinous process fracture and C6-C7 body fractures. Thirteen patients with negative lateral c-spine screens (sensitivity, 61%) were diagnosed with cervical spine injury. We evaluated 463 patients with blood ethanol levels greater than 100 mg/dL, and 6 (1.3%) were diagnosed with c-spine injury. No injuries were missed on clinical examination in this subgroup with elevated blood ethanol levels. CONCLUSIONS: 1) Clinical examination of the neck can reliably rule out significant cervical spine injury in the awake and alert blunt trauma patient. Addition of lateral c-spine x-ray does not improve the sensitivity of clinical examination in the diagnosis of significant cervical spine injury. 2) Elevated ethanol level is not a contraindication to the use of clinical examination as the screening tool for cervical spine injury. Level of consciousness, as determined by Glasgow Coma Score, is a more effective criterion to dictate a screening method for cervical spine injury.


Assuntos
Vértebras Cervicais/lesões , Exame Neurológico , Fraturas da Coluna Vertebral/diagnóstico , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Etanol/sangue , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/diagnóstico , Traumatismo Múltiplo/cirurgia , Estudos Prospectivos , Sensibilidade e Especificidade , Fraturas da Coluna Vertebral/cirurgia , Ferimentos não Penetrantes/cirurgia
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