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1.
Expert Opin Drug Saf ; 19(1): 69-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31847608

RESUMO

Introduction: Psoriatic arthritis (PsA) is characterized by chronic inflammation mediated by pro-inflammatory cytokines, with clinical features resulting from dysfunctional integrated signaling pathways affecting different constituents of the immune system. Increased understanding of the processes responsible for enthesitis, synovial inflammation, joint erosion, and new bone formation during PsA has led to development of biologic therapies targeting these cytokines. There is an increased risk of opportunistic infections in patients with PsA, and this risk is increased further with targeted biologic therapy.Areas covered: This paper reviews the role of the interleukin (IL)-12, IL-23 and IL-17 axis in the pathogenesis of PsA. The data suggest that ustekinumab is associated with a low risk of infections in patients with PsA, including tuberculosis or hepatitis reactivation. No live vaccines can be safely administered; ustekinumab is contraindicated/cannot be given with live vaccines. However, long-term treatment with ustekinumab does not impair the immune response to these vaccines when administered after an appropriate interval.Expert opinion: Ustekinumab is associated with a low risk of serious and opportunistic infections. More research is needed to confirm these findings specifically in patients with PsA, and comparative studies are needed to investigate the relative risk of infection with different biologics.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Infecções Oportunistas/etiologia , Ustekinumab/efeitos adversos , Animais , Artrite Psoriásica/complicações , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Humanos , Interleucina-12/imunologia , Interleucina-17/imunologia , Interleucina-23/imunologia , Infecções Oportunistas/epidemiologia , Ustekinumab/administração & dosagem
2.
J Drugs Dermatol ; 18(10): 1059-1060, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603636

RESUMO

To the Editor: Patients with psoriasis are at increased risk of developing non melanoma skin cancer (NMSC), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).1,2 The risk is especially elevated among those who previously received systemic treatment or phototherapy.2 Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors.3


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Psoríase/tratamento farmacológico , Neoplasias Cutâneas/epidemiologia , Produtos Biológicos/efeitos adversos , Carcinoma Basocelular/induzido quimicamente , Carcinoma de Células Escamosas/induzido quimicamente , Humanos , Estudos Longitudinais , Metotrexato/efeitos adversos , Sistema de Registros/estatística & dados numéricos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamente
3.
Expert Opin Drug Metab Toxicol ; 15(11): 913-925, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31623470

RESUMO

Introduction: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) and other cytokines in the pathogenesis of psoriasis have driven the introduction of biologic agents targeting specific immune mediators in everyday clinical practice. TNF α inhibitors are a consolidated treatment option for patients with moderate-to-severe disease with remarkable efficacy and a reassuring safety profile.Areas covered: The PubMed database was searched using combinations of the following keywords: psoriasis, TNF α inhibitors, biologic therapy, pharmacodynamics, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects. The aim of this review is to describe the pharmacodynamic profile of anti-TNF α inhibitors, currently approved by the European Medicines Agency (EMA) for the treatment of psoriasis, focusing on related clinical implications, also in comparison to the new generation biological therapies targeting the interleukin 23/interleukin 17 axis.Expert opinion: Pharmacodynamics of TNF α inhibitors should be fully considered in planning patient's therapy strategies, especially in case of secondary failures, poor adherence to treatment, instable psoriasis, high risk of infection, pregnant or lactating women, metabolic comorbidities, coexistence of other immune-mediated inflammatory diseases.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Desenvolvimento de Medicamentos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Adesão à Medicação , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
4.
J Drugs Dermatol ; 18(10): 1012-1018, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584780

RESUMO

Background: The use of topical therapy is a key component in the management of almost all psoriasis patients. Topicals are considered first-line therapy for mild disease and are having an increasing role in moderate or severe psoriasis as an integral part of combination therapy. Halobetasol has been shown be effective in moderate or severe localized plaque psoriasis, and tazarotene affords important effects on epidermal hyperproliferation that may be important in more severe disease. Objective: To investigate the efficacy, safety and tolerability of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its vehicle in patients with severe localized plaque psoriasis (as defined by an Investigator Global Assessment (IGA) of 4 and Body Surface Area (BSA) of 3%-12%. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Sixty-two patients with severe localized psoriasis (mean BSA 7.4) randomized (2:1) to receive HP/TAZ lotion or vehicle, once-daily for 8 weeks, with a 4-week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of 'clear' or 'almost clear'), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, BSA, reduction in mean baseline IGAxBSA and achievement of a clinically meaningful response (number of patients who achieved at least a 75% improvement in IGAxBSA). Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. Results: By week 8, 34.8% of patients were treatment successes compared with 0.0% on vehicle (P=0.004). HP/TAZ lotion was also significantly superior in reducing psoriasis signs and symptoms and improving BSA. At week 8, 47.4% (erythema), 66.4% (plaque elevation), and 65.4% (scaling) subjects achieved at least a 2-grade improvement, compared with 14.0% (P=0.016), 14.8% (P<0.001) and 14.7% (P<0.001) respectively with vehicle. Patients treated with HP/TAZ lotion achieved a 32.8% reduction in baseline mean BSA, compared with a 39.6% increase with vehicle (P=0.013). HP/TAZ lotion achieved a statistically significant superior reduction in mean IGAxBSA compared to vehicle from week 2 (P<0.001 versus vehicle). By week 8, almost half of the patients treated with HP/TAZ lotion achieved a clinically meaningful response (IGAxBSA-75) and a 52.9% reduction in mean IGAxBSA score compared with a 17.5% increase in those patients treated with vehicle (P<0.001). One patient (2.6%) treated with HP/TAZ lotion discontinued due to AE. Most frequently reported treatment related AEs were application site pain (7.9%), contact dermatitis (5.3%) and pruritus (5.3%). Conclusions: HP/TAZ lotion provides significantly greater efficacy than vehicle that is both rapid and sustained, in patients with severe localized plaque psoriasis, with good tolerability and safety over 8 weeks' once-daily use. J Drugs Dermatol. 2019;18(10):1012-1018.


Assuntos
Clobetasol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Psoríase/tratamento farmacológico , Creme para a Pele/administração & dosagem , Adulto , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Dermatite de Contato/epidemiologia , Dermatite de Contato/etiologia , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Nicotínicos/efeitos adversos , Dor/epidemiologia , Dor/etiologia , Prurido/epidemiologia , Prurido/etiologia , Psoríase/diagnóstico , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Resultado do Tratamento
5.
J Drugs Dermatol ; 18(10): 1029-1036, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584782

RESUMO

Background: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Topical corticosteroids (TCS) are the mainstay of treatment. Long-term safety remains a concern, limiting use, and posttreatment flare is common. Recently data were reported on the use of halobetasol propionate (HP) 0.01% lotion in moderate or severe localized plaque psoriasis, once-daily for 8 weeks. In addition, a 2-week label-restricted study reported comparable efficacy to HP 0.05% cream. Data evaluating efficacy in specific locations has not been reported and while psoriasis commonly affects lower extremities treatment can be more problematic and burden of disease heightened. Objective: To investigate the efficacy of a once-daily application of HP 0.01% lotion in comparison with its vehicle in patients with moderate-to-severe plaque psoriasis of the lower extremities. Methods: A post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate or severe psoriasis. Subjects (N=234) where the leg was identified as the target lesion were randomized (2:1 ratio) to receive HP 0.01% lotion or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline) in each individual sign of psoriasis (erythema, plaque elevation, and scaling) at the target lesion (leg) and overall treatment outcomes including at least a 2-grade improvement from baseline in the Investigator Global Assessment (IGA) score, and 'clear' or 'almost clear', improvement in Body Surface Area (BSA) and reduction in IGAxBSA. Quality of Life (QoL) was assessed using the Dermatology Life Quality Index (DLQI) at baseline, week 4, 8, and 12. Results: At the end of the 8-week treatment period, more than half of subjects had achieved treatment success, with 52.1%, 55.5%, and 58.2% of subjects achieving at least a 2-grade reduction in erythema, plaque elevation and scaling severity on the leg, compared with 15.7% and 22.9%, and 22.2% of those treated with vehicle (P<0.001). In addition, overall treatment success (IGA) was achieved in 37.1% of these subjects who had been treated with HP 0.01% lotion compared with 8.4% treated with vehicle (P<0.001); with a corresponding 34.2% reduction in baseline BSA and 50.5% change in mean baseline IGAxBSA (both P<0.001 versus vehicle). Overall, a clinically relevant improvement in QoL was achieved by week 4; by week 8 37.7% of subjects where the leg was the target lesion had a clinically meaningful improvement in disease severity (IGAxBSA-75). Conclusions: In conclusion, halobetasol propionate 0.01% lotion provides statistically significant efficacy following 8 weeks' therapy compared with vehicle in subjects where the leg was identified as the target lesion, with clinically relevant improvements in QoL and more than a third of subjects achieving a clinically meaningful result. J Drugs Dermatol. 2019;18(10):1029-1036.


Assuntos
Clobetasol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Creme para a Pele/administração & dosagem , Adulto , Idoso , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Resultado do Tratamento
6.
J Drugs Dermatol ; 18(9): 924-927, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524349

RESUMO

Acne is primarily an inflammatory disease. Anti-inflammatory dose doxycycline (40mg: 30mg immediate release and 10mg delayed release beads) is approved for the treatment of rosacea but with demonstrated efficacy for acne. Fixed combination adapalene 0.3% and benzoyl peroxide 2.5% gel is a once-daily formulation approved for the topical management of acne vulgaris. It has both anti-inflammatory and anti-comedogenic properties. Options for management of severe acne are somewhat limited; many patients are not candidates for or refuse treatment with isotretinoin. Systemic antibiotics may be indicated; acne treatment guidelines emphasize antibiotic stewardship in light of increasing concerns about antibiotic resistance and call for the judicious use of conventional systemic antibiotics. This single-center, open label pilot study involving 20 subjects with severe acne assessed the effects of combination treatment using anti-inflammatory dose doxycycline plus adapalene 0.3% and benzoyl peroxide 2.5% gel on IGA scores as well as inflammatory lesion, non-inflammatory lesion, and nodule counts. By week 12, 95% of subjects had at least a 2-grade improvement in IGA scores. Reductions in inflammatory and non-inflammatory lesion counts were statistically significant beginning at week 4 and continuing through week 12. By week 4, the percentage of patients with 0 nodules was 70%, compared to baseline of 20%. Further improvements were seen through week 12. Treatment was well-tolerated with no serious treatment-related adverse events. Combination treatment with anti-inflammatory dose doxycycline plus combination adapalene 0.3% and benzoyl peroxide 2.5% gel is safe and effective for management of severe acne. J Drugs Dermatol. 2019;18(9):924-927.


Assuntos
Acne Vulgar/tratamento farmacológico , Combinação Adapaleno e Peróxido de Benzoil/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Doxiciclina/administração & dosagem , Combinação Adapaleno e Peróxido de Benzoil/efeitos adversos , Administração Cutânea , Administração Oral , Adolescente , Adulto , Criança , Fármacos Dermatológicos/efeitos adversos , Relação Dose-Resposta a Droga , Doxiciclina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Géis , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
7.
Expert Opin Drug Saf ; 18(11): 1031-1041, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479282

RESUMO

Introduction: Psoriasis is a chronic inflammatory disease and affects about 10% of the world's population. Psoriasis is associated with a number of comorbidities. Biologic therapies for the treatment of moderate-severe plaque psoriasis include tumor necrosis factor α inhibitors (TNFi), and newer molecules targeting IL-12 and 23, blocking p40 subunit, or targeting subunit p19 of IL-23 and other molecules blocking IL-17A, or directed against the IL-17 receptor. Areas covered: Anti-interleukin drugs show great improvement in disease control and on the other hand are not affected by important adverse reactions of older compounds. Approach to chronic disease affected patients, in particular, and to patients with multiple comorbidities is revolutionized by novel molecules that are safer and more manageable. Expert opinion: A recent work suggests that pro-fibrogenic cytokines, IL-17, might be important player of liver damage and even in regulation of obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Choosing to interfere with IL-23/Il-17 axis, definitely, is like acting against psoriatic march and in a parallel way against its comorbidities.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Produtos Biológicos/imunologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/imunologia , Humanos , Interleucina-12/imunologia , Interleucina-17/imunologia , Interleucina-23/imunologia , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença
8.
BMJ Case Rep ; 12(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31413050

RESUMO

Herpes simplex virus (HSV) encephalitis affects 2-4 people per million/year. Immunocompomised patients can have atypical presentations of HSV encephalitis, including a lack of cerebrospinal fluid (CSF) pleocytosis. We present the case of a patient who was receiving ustekinumab therapy for psoriasis which inhibits interleukin (IL)-12 and IL-23 signalling pathways. The initial presentation was suggestive of encephalitis, but he was discharged prior to the reporting of HSV positivity due to the lack of CSF pleocytosis. On representation, he had worsening symptoms and imaging showed midline shift, indicating cerebral oedema despite the immunosupressant effects of ustekinumab. He required intensive care unit support and treatment with high dose aciclovir and dexamethasone; after a month of treatment he made a good recovery. This case is the first to report a link between ustekinumab and HSV encephalitis, and also emphasises that imunocompromised patients can lack CSF pleocytosis and develop significant cerebral oedema which responds to immune suppression.


Assuntos
Anti-Inflamatórios/uso terapêutico , Edema Encefálico/diagnóstico , Fármacos Dermatológicos/efeitos adversos , Encefalite por Herpes Simples/diagnóstico , Hospedeiro Imunocomprometido , Ustekinumab/efeitos adversos , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Edema Encefálico/induzido quimicamente , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/tratamento farmacológico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Diagnóstico Diferencial , Encefalite por Herpes Simples/líquido cefalorraquidiano , Encefalite por Herpes Simples/induzido quimicamente , Encefalite por Herpes Simples/tratamento farmacológico , Humanos , Masculino , Psoríase/tratamento farmacológico
9.
BMJ Case Rep ; 12(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31413063

RESUMO

This case report presents a patient who, while undergoing oral isotretinoin therapy for acne vulgaris, developed onychocryptosis and asymptomatic external urethritis. These uncommon adverse events are not well-documented in medical literature. While his urethritis spontaneously resolved, his onychocryptosis symptoms necessitated surgical intervention. This report illustrates both cosmetic and functional adverse effects of isotretinoin and provides insight into the progression of these reactions over time.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Dermatoses do Pé/diagnóstico , Isotretinoína/efeitos adversos , Onicomicose/diagnóstico , Uretrite/diagnóstico , Acne Vulgar/tratamento farmacológico , Administração Oral , Adolescente , Diagnóstico Diferencial , Dermatoses do Pé/induzido quimicamente , Dermatoses do Pé/complicações , Humanos , Masculino , Onicomicose/induzido quimicamente , Onicomicose/complicações , Uretrite/induzido quimicamente , Uretrite/complicações
10.
Expert Rev Clin Pharmacol ; 12(9): 851-857, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31460804

RESUMO

Introduction: The interleukin (IL)-23 and IL-17 pathway is closely related to the pathogenesis of psoriasis. This pathway is considered to be an important target for treating psoriasis. Risankizumab can selectively inhibit IL-23p19 subunit and for the treatment of psoriasis. This article aims to review risankizumab and provides reference for clinicians. Areas covered: The chemical property, mechanism of action, pharmacokinetics, clinical efficacy, safety of risankizumab was introduced in this paper. A PubMed search using the terms 'risankizumab,' 'IL-23,' 'p19 subunit,' and 'psoriasis,' was performed, and the results were screened for the most relevant English language publications. Expert opinion: Risankizumab is a humanized IgG monoclonal antibody that binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Clinical trials showed that risankizumab was significantly more effective than ustekinumab. Risankizumab was well tolerated, upper respiratory tract infection was the common adverse reactions. Therefore, the market of risankizumab provides an important therapeutic means for psoriasis.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Humanos , Interleucina-23/imunologia , Psoríase/imunologia , Psoríase/patologia , Ustekinumab/administração & dosagem
11.
J Drugs Dermatol ; 18(8): 790-796, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424709

RESUMO

BACKGROUND: A novel foam formulation of halobetasol propionate, 0.05% (HBP-Foam) has been developed to treat plaque psoriasis in patients who prefer a thermostable topical foam with low application shear that allows for easier coverage over large and/or hirsute areas than existing formulations. OBJECTIVE: To determine the safety and effectiveness of HBP-Foam in subjects with plaque psoriasis. METHODS: Two randomized, double-blind, vehicle-controlled clinical studies were conducted in 560 adult subjects with moderate to severe plaque psoriasis. Subjects applied the assigned test article to all psoriatic plaques twice daily for 14 days. The key efficacy measures were the proportion of subjects with "treatment success," defined as those subjects that achieved a score of 0 (clear) or 1 (almost clear) and at least a two-grade improvement compared to baseline for the Investigator's Global Assessment (IGA) and for the clinical signs of psoriasis (plaque elevation, scaling, and erythema) as well as pruritus. Safety measurements included adverse events and local skin reactions in the treatment area. RESULTS: HBP-Foam was statistically superior to vehicle in achieving "Treatment Success" in 25.3% and 30.7% vs 3.9% and 7.4% (P<0.001) in Studies 1 and 2, respectively. Pruritus scores statistically improved by over 30% in HBP-Foam treated subjects. In addition, these subjects experienced a significant reduction in the clinical signs of psoriasis (plaque elevation, scaling, and erythema). In contrast, in the vehicle groups the decrease in psoriasis-related signs was generally not observed. Safety outcomes were unremarkable and similar in both the HBP-Foam and vehicle treatment groups. CONCLUSIONS: These results demonstrate the safety and effectiveness of HBP-Foam in the treatment of plaque psoriasis. Furthermore, this novel foam formulation has demonstrable for its ease of application over large and/or hairy treatment areas. ClinicalTrials.gov Registration: NCT02742441 NCT02368210


Assuntos
Clobetasol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Veículos Farmacêuticos/administração & dosagem , Prurido/tratamento farmacológico , Psoríase/tratamento farmacológico , Vasoconstritores/administração & dosagem , Adulto , Idoso , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veículos Farmacêuticos/efeitos adversos , Prurido/diagnóstico , Prurido/etiologia , Psoríase/complicações , Psoríase/diagnóstico , Índice de Gravidade de Doença , Pele , Resultado do Tratamento , Vasoconstritores/efeitos adversos
12.
J Drugs Dermatol ; 18(8): 815-820, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424713

RESUMO

BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Topical corticosteroids (TCS) are the mainstay of treatment. Long-term safety remains a concern, limiting use and recurrence is common. Tazarotene has also been shown to be effective in psoriasis, with efficacy maintained several weeks posttreatment. Fixed combination therapy with TCS and tazarotene may improve psoriasis signs and maintain efficacy between treatment sessions. OBJECTIVE: To investigate the maintenance of effect posttreatment with a once-daily application of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in comparison with vehicle in patients with moderate or severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe psoriasis (N=418). Patients randomized (2:1) to receive HP/TAZ lotion or vehicle, once-daily for 8 weeks with a 4 week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score, and 'clear' or 'almost clear'), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, and maintenance of improvements in Body Surface Area (BSA), IGAxBSA and clinically meaningful benefit (IGAxBSA-75). RESULTS: At week 8, 40.7% of patients achieved treatment success with HP/TAZ lotion, compared with 9.9% treated with vehicle (P<0.001). Four weeks posttreatment, 33.3% of patients achieved treatment success. Two thirds of patients (63%) who were treatment successes at week 8 remained treatment successes posttreatment. In addition, up to 20% of patients who were not treatment successes at week 8 became treatment successes by the end of the study. Three-quarters of patients maintained BSA improvements or reported further reductions in BSA that seemed to be unrelated to baseline BSA severity. At the end of the 4 week posttreatment period, patients who had been treated with HP/TAZ lotion achieved a 46.6% reduction in IGAxBSA, compared with 7.9% on vehicle. 41.7% of patients achieved a clinically meaningful effect at week 8 and this was maintained posttreatment. LIMITATIONS: The studies only had a 4 week follow-up period. CONCLUSIONS: In conclusion, HP 0.01%/TAZ 0.045% lotion provides effective maintenance of efficacy over a 4 week posttreatment period.


Assuntos
Clobetasol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Psoríase/tratamento farmacológico , Creme para a Pele/administração & dosagem , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Seguimentos , Humanos , Ácidos Nicotínicos/efeitos adversos , Psoríase/diagnóstico , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Resultado do Tratamento
13.
BMJ Case Rep ; 12(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420435

RESUMO

A 26-year-old man undergoing therapy with 45 mg ustekinumab (Stelara) for chronic psoriasis vulgaris was referred by his general practitioner to an infectious diseases department for fatigue, fever, night sweating, generalised lymphadenomegaly and unexplained weight loss. Physical examination revealed bilateral occipital, cervical, axillary and inguinal lymphadenomegalies in addition to splenomegaly. Preliminary investigation revealed elevated Plasmodium lactate dehydrogenase and an inversion of the CD4/CD8 ratio. Whole-body spiral CT scanning with and without contrast showed splenomegaly and highlighted supradiaphragmatic and subdiaphragmatic lymphadenopathies. A complete Infectious Disease Test Panel revealed high levels of anti-Toxoplasma gondii antibodies. Immunoglobulin G avidity was negative. Peripheral blood lymphocyte phenotyping was performed to exclude underlying lymphatic neoplasia. The diagnosis of severe acute toxoplasmosis infection in the setting of immune response modifiers was made. Ustekinumab was suspended indefinitely and the patient underwent monthly serological tests to monitor the immune response until all symptoms resolved and the serological testing was negative for Toxoplasma.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Psoríase/tratamento farmacológico , Toxoplasma , Toxoplasmose/induzido quimicamente , Ustekinumab/efeitos adversos , Doença Aguda , Adulto , Humanos , Masculino , Psoríase/microbiologia
14.
Skin Therapy Lett ; 24(4): 1-4, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31339678

RESUMO

The interleukin (IL)-17 inhibitors have proven to be highly effective in the treatment of psoriasis. The most recently approved agent, brodalumab, had few cases of suicidal behavior, including completed suicide, in the phase 3 clinical program leading both the US FDA and Health Canada to add a boxed warning to its label. This raises the importance of identifying the psychiatric comorbidities associated with psoriasis. It is also necessary to critically examine the data from the brodalumab clinical trial program to determine whether there is enough information to establish causality and whether other factors, other than the drug, could be playing a role.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Psoríase/tratamento farmacológico , Ideação Suicida , Suicídio/estatística & dados numéricos , Anticorpos Monoclonais Humanizados/administração & dosagem , Canadá , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Rotulagem de Medicamentos , Humanos , Interleucina-17/imunologia
15.
J Dermatol ; 46(9): 752-758, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342560

RESUMO

The 52-week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient-reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double-blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Grupo com Ancestrais do Continente Asiático , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/patologia , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/patologia , Fatores de Tempo , Ustekinumab/efeitos adversos
17.
Pediatr Rheumatol Online J ; 17(1): 36, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31287007

RESUMO

BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is a rare autoinflammatory disease, caused by gain of function mutation in NLRP3 resulting in excess production of interleukin-1 (IL-1). Canakinumab is a human monoclonal antibody against Interleukin-1 beta (IL-1ß), licensed for the treatment of CAPS. The objective of the study was to describe the feasibility and cost-effectiveness of a canakinumab vial-sharing programme for paediatric patients with CAPS. METHOD: Retrospective case series and clinical service description of a national specially commissioned CAPS clinic at Great Ormond Street Hospital (GOSH). Effectiveness was assessed using a CAPS disease activity score (DAS) and serum amyloid A protein (SAA). Adverse events were collected to determine safety. The number of canakinumab vials saved was considered when investigating the cost-effectiveness of vial-sharing. RESULTS: Nineteen/20 (95%) of our paediatric patients achieved minimally active clinical disease activity with canakinumab monotherapy; and 75% achieved both minimally active clinical disease and serological remission using a pre-specified definition based on the CAPS DAS and SAA level. Canakinumab was well tolerated, with only one child developing an infection requiring hospitalisation during the study. Canakinumab vial sharing resulted in 117 vials of canakinumab saved over a 24-month period, equating to a direct drug-related cost saving of £1,385,821, and a conservative estimated 5-year cost-saving of £3,464,552.50. CONCLUSION: We provide further evidence for the effectiveness and safety of canakinumab in children with CAPS, and highlight the cost-effectiveness of a vial-sharing programme for this high cost medicine. We suggest that this could have important implications for the delivery of other high cost medicines used in paediatric practice.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Adolescente , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/economia , Criança , Pré-Escolar , Análise Custo-Benefício , Síndromes Periódicas Associadas à Criopirina/economia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/economia , Custos de Medicamentos , Estudos de Viabilidade , Feminino , Humanos , Injeções Subcutâneas , Masculino , Uso Comum de Agulhas e Seringas/economia , Estudos Retrospectivos , Resultado do Tratamento
18.
J Drugs Dermatol ; 18(7): 642-648, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329402

RESUMO

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Hiperpigmentação/tratamento farmacológico , Melaninas/antagonistas & inibidores , Creme para a Pele/administração & dosagem , Preparações Clareadoras de Pele/administração & dosagem , Adulto , Idoso , Fármacos Dermatológicos/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Melaninas/metabolismo , Pessoa de Meia-Idade , Retinoides/administração & dosagem , Retinoides/efeitos adversos , Envelhecimento da Pele/efeitos dos fármacos , Creme para a Pele/efeitos adversos , Creme para a Pele/química , Preparações Clareadoras de Pele/efeitos adversos , Preparações Clareadoras de Pele/química , Pigmentação da Pele/efeitos dos fármacos , Resultado do Tratamento
19.
J Med Case Rep ; 13(1): 257, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31358038

RESUMO

BACKGROUND: The utilization of monoclonal antibodies has become more widespread over the past decade. However, the development of non-caseating granulomas with the use of monoclonal antibodies, such as ustekinumab, is not widely reported in the literature. CASE PRESENTATION: We report a case of a 50-year-old Caucasian male who presented complaining of weight loss and shortness of breath. He was receiving ustekinumab for refractory psoriasis but had no other significant medical comorbidities. On physical examination, reduced breath sounds on the right side were noted. Blood cultures were drawn on presentation and came back negative in 48 hours. A chest computed tomography scan revealed a large right lung mass in addition to right-sided pleural effusion. Therapeutic thoracocentesis was done; fluid cytology and analysis were negative for malignancy, acid-fast bacilli, or fungal infections. A positron emission tomography scan showed multifocal radiotracer uptake including within right lung mass, multiple bones, lymph nodes, liver and spleen. Biopsies showed hyalinized non-necrotizing granulomas. Immunohistochemical stains for AE1/AE3, cytokeratin 7 and 20, and thyroid transcription factor 1, were all negative. He was started on steroid therapy, and ustekinumab was discontinued and the follow-up computed tomography after a few months showed substantial improvement. However, over the course of next 4 months patient developed hepatic dysfunction and recurrent ascites and ultimately underwent transjugular intrahepatic portosystemic shunt placement. Furthermore, he was started on azathioprine and steroids were tapered. He improved clinically and was discharged from our hospital within a week. CONCLUSIONS: This case highlights the need for careful consideration of patient medication history while evaluating the possible differential diagnoses that may contribute to a patient's presentation.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Granuloma/induzido quimicamente , Ustekinumab/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Psoríase/tratamento farmacológico , Sarcoidose/diagnóstico , Tomografia Computadorizada por Raios X , Ustekinumab/administração & dosagem
20.
Clin Drug Investig ; 39(8): 799-803, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168691

RESUMO

BACKGROUND: Up to December 2018, eight cases of new-onset inflammatory bowel disease (IBD) were reported in the literature in patients being treated with secukinumab, an interleukin-17A antagonist prescribed for dermatologic or rheumatologic indications. The duration of secukinumab treatment ranged from a single administration to 12 months of treatment. OBJECTIVE: The aim of our investigation was to estimate the cumulative incidence of new-onset IBD in patients treated with secukinumab for either dermatologic or rheumatologic indications. METHODS: We carried out a survey among the dermatology and rheumatology centres in the Sicilian region (Italy) in order to identify the number of patients treated with secukinumab in the previous 24 months (November 2016-November 2018), and to understand how many of these patients eventually developed IBD after the start of secukinumab therapy. RESULTS: Overall, four cases of IBD during secukinumab treatment were identified, with higher variability in time to onset compared with what has been previously reported, i.e. from 1 month to 5 years of secukinumab exposure. Overall, 434 patients were treated with secukinumab in Sicily between November 2016 and November 2018, and approximately 1% of these patients developed new-onset IBD. CONCLUSIONS: Careful clinical examination of patients with respect to possible susceptibility to IBD prior to secukinumab therapy is advised.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Doenças Inflamatórias Intestinais/induzido quimicamente , Interleucina-17/antagonistas & inibidores , Adolescente , Adulto , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Incidência , Itália , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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