RESUMO
BACKGROUND: Rapid skin improvement is a key treatment goal of patients with moderate-to-severe psoriasis (PsO). OBJECTIVES: To compare the speed of clinical improvement of approved biologics on the symptoms and signs of psoriasis assessed by patients using the validated Psoriasis Symptoms and Signs Diary (PSSD) through 12 weeks. METHODS: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study that compares the effectiveness of anti-interleukin (IL)-17A biologics versus other biologics, together with pairwise comparisons of ixekizumab versus five individual biologics in patients with PsO. Using the PSSD 7-day recall period, patients assessed the symptoms (itch, skin tightness, burning, stinging and pain) and signs (dryness, cracking, scaling, shedding/flaking, redness and bleeding) of their psoriasis (0-10). Symptom and sign summary scores (0-100) are derived from the average of individual scores. Percentage change in summary scores and proportion of patients with clinically meaningful improvements (CMI) in PSSD summary and individual scores are evaluated weekly. Longitudinal PSSD data are reported as observed with treatment comparisons analysed using mixed model for repeated measures (MMRM) and generalized linear mixed models (GLMM). RESULTS: Across cohorts and treatments, eligible patients (n = 1654) had comparable baseline PSSD scores. From Week 1, the anti-IL-17A cohort achieved significantly larger score improvements in PSSD summary scores and a higher proportion of patients showed CMIs compared to the other biologics cohort through 12 weeks. Lower PSSD scores were associated with a greater proportion of patients reporting their psoriasis as no longer impacting their quality-of-life (DLQI 0,1) and a high level of clinical response (PASI100). Results also indicate a relationship between an early CMI in PSSD score at Week 2 and PASI100 score at Week 12. CONCLUSIONS: Treatment with anti-IL-17A biologics, particularly ixekizumab, resulted in rapid and sustained patient-reported improvements in psoriasis symptoms and signs compared with other biologics in a real-world setting.
Assuntos
Produtos Biológicos , Psoríase , Humanos , Anticorpos Monoclonais/uso terapêutico , Estudos Prospectivos , Índice de Gravidade de Doença , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Produtos Biológicos/uso terapêutico , Dor/tratamento farmacológico , Resultado do TratamentoRESUMO
PURPOSE: Psoriasis is a chronic skin condition that affects approximately 1-3% of the world's population and is known to decrease patients' quality of life. However, it is yet to be ascertained whether the specific location of psoriatic lesions on the body influences one's quality of life. METHODS: A systematic review was conducted with a search of MEDLINE, EMBASE, and Web of Science databases. Only non-case report and non-review studies with explicitly stated body regions affected by psoriasis were included in the review. FINDINGS: Psoriatic patches and plaques in different areas of the body were not found to influence patients' quality of life to differing extents. CONCLUSIONS: While the body of evidence is limited and presents unstandardized results, the results of this review point to the fact that all psoriatic patches and plaques decrease patients' quality of life, with neither one region doing so to a significantly greater extent than another.
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Psoríase , Qualidade de Vida , Humanos , Psoríase/patologia , Doença CrônicaRESUMO
PURPOSE: Psoriasis is a chronic skin condition that affects approximately 1-3% of the world's population and is known to decrease patients' quality of life. However, it is yet to be ascertained whether the specific location of psoriatic lesions on the body influences one's quality of life. METHODS: A systematic review was conducted with a search of MEDLINE, EMBASE, and Web of Science databases. Only non-case report and non-review studies with explicitly stated body regions affected by psoriasis were included in the review. FINDINGS: Psoriatic patches and plaques in different areas of the body were not found to influence patients' quality of life to differing extents. CONCLUSIONS: While the body of evidence is limited and presents unstandardized results, the results of this review point to the fact that all psoriatic patches and plaques decrease patients' quality of life, with neither one region doing so to a significantly greater extent than another.
Assuntos
Psoríase , Qualidade de Vida , Humanos , Psoríase/patologia , Doença CrônicaAssuntos
Fármacos Dermatológicos , Psoríase , Anticorpos Monoclonais Humanizados/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Etanercepte/efeitos adversos , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/efeitos adversosRESUMO
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, a novel RNA virus that was declared a global pandemic on 11 March 2020. The efficiency of infection with SARS-CoV-2 is reflected by its rapid global spread. The SARS-CoV-2 pandemic has implications for patients with inflammatory skin diseases on systemic immunotherapy who may be at increased risk of infection or more severe infection. This position paper is a focused examination of current evidence considering the mechanisms of action of immunotherapeutic drugs in relation to immune response to SARS-CoV-2. We aim to provide practical guidance for dermatologists managing patients with inflammatory skin conditions on systemic therapies during the current pandemic and beyond. Considering the limited and rapidly evolving evidence, mechanisms of action of therapies, and current knowledge of SARS-CoV-2 infection, we propose that systemic immunotherapy can be continued, with special considerations for at risk patients or those presenting with symptoms.
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COVID-19/epidemiologia , Dermatite/terapia , Imunoterapia , COVID-19/complicações , COVID-19/terapia , Humanos , Padrões de Prática Médica , Medição de RiscoRESUMO
BACKGROUND: Significantly more patients with moderate-to-severe plaque psoriasis treated with the interleukin (IL)-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab in the IXORA-R head-to-head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. OBJECTIVES: To compare skin and nail clearance and patient-reported outcomes for ixekizumab vs. guselkumab, up to week 24. METHODS: IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran-Mantel-Haenszel test stratified by pooled site. Time-to-first-event comparisons were performed using Kaplan-Meier analysis, and P-values were generated using adjusted log-rank tests stratified by treatment group. Cumulative days at clinical and patient-reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). RESULTS: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference -2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. CONCLUSIONS: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate-to-severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab.
Assuntos
Psoríase , Adulto , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: The relevance of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of psoriasis has not been studied previously. GM-CSF is important in the initiation and maintenance of chronic inflammatory processes. OBJECTIVES: To investigate the clinical use of GM-CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM-CSF inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS: A phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group, dose-finding, proof-of-concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point - the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) - was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777. RESULTS: In total, 122 patients were enrolled and 106 (86·9%) completed the double-blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration-time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment-related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis. CONCLUSIONS: GM-CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies.
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Medicamentos Biossimilares/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Dermatologistas/psicologia , Aprovação de Drogas , Saúde Global , Humanos , Legislação de Medicamentos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Vigilância de Produtos ComercializadosRESUMO
Biosimilars are drugs that are similar, but not identical, to originator biologics. Preclinical analytical studies are required to show similarity on a molecular and structural level, but efficacy and safety studies in humans are essential to determining biosimilarity. In this review, written by members of the International Psoriasis Council, we discuss how biosimilars are evaluated in a clinical setting, with emphasis on extrapolation of indication, interchangeability and optimal clinical trial design.
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Medicamentos Biossimilares/uso terapêutico , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Ensaios Clínicos como Assunto , Aprovação de Drogas , Humanos , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. A Phase 3 withdrawal/re-treatment study (NCT01186744; OPT Retreatment) showed tofacitinib re-treatment was effective in patients with chronic plaque psoriasis. OBJECTIVES: To describe the effects of tofacitinib withdrawal/re-treatment on health-related quality of life (HRQoL) and disease symptoms measured by patient-reported outcomes (PROs). METHODS: The study was divided into initial treatment, treatment withdrawal, and re-treatment periods. Initial treatment: patients were randomized to receive tofacitinib 5 (n = 331) or 10 mg (n = 335) BID for 24 weeks. Treatment withdrawal: patients who achieved both ≥ 75% reduction in Psoriasis Area and Severity Index (PASI) score from baseline and Physician's Global Assessment of 'clear'/'almost clear' at Week (W)24 received placebo (withdrawal) or the previous dose (continuous treatment). Re-treatment: at relapse (> 50% loss of W24 PASI response) or at W40, patients received their initial tofacitinib dose. PROs included: Dermatology Life Quality Index (DLQI), Itch Severity Item (ISI), Short Form-36 (SF-36) and Patient's Global Assessment (PtGA). RESULTS: After initial treatment with tofacitinib 5 and 10 mg BID, substantial and significant improvements were reported for mean DLQI (baseline: 12.6 and 12.6; W24: 5.1 and 2.6) and ISI (baseline: 6.7 and 6.9; W24: 2.9 and 1.6). Patients continuously treated with tofacitinib 5 and 10 mg BID maintained those improvements through Week 56 (DLQI: 3.0 and 2.1; ISI: 2.3 and 1.4). By W40, patients withdrawn from tofacitinib 5 and 10 mg BID showed worsening in DLQI (5.0 and 6.2) and ISI (3.7 and 4.0) scores; improvements were regained upon re-treatment (W56, DLQI: 3.4 and 2.4; ISI: 2.2 and 1.6). Similar results were reported for PtGA and SF-36. CONCLUSION: Continuous tofacitinib treatment provided sustained improvement in HRQoL and disease symptoms. Patients randomized to treatment withdrawal lost initial improvements. Upon re-treatment, improvements were recaptured to levels comparable to those seen with continuous treatment.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Piperidinas/administração & dosagem , Psoríase/tratamento farmacológico , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Doença Crônica , Método Duplo-Cego , Humanos , Psoríase/fisiopatologia , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
Biosimilars, sometimes called 'generic biologics', are no longer a vision for the future but a present-day reality. Drug manufacturers and regulatory authorities are charged with ensuring that these products are safe and effective. Because biologically produced medications are large, complex proteins, many factors affect the quality of the end product, including glycosylation and presence of impurities, and thus many factors need to be compared between an emerging biosimilar and its originator biologic. Indeed, preclinical analytical assessments to determine similarity to an originator biologic are critical and are considered to be the foundation for regulatory approval of biosimilars. Here, the science behind the preclinical development of biosimilars is discussed by members of the International Psoriasis Council, and suggestions are put forth to try to ensure that future biosimilars are produced in a high quality and standardized manner.
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Medicamentos Biossimilares/uso terapêutico , Psoríase/tratamento farmacológico , Medicamentos Biossimilares/análise , Linhagem Celular , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Proteínas Recombinantes/análise , Proteínas Recombinantes/biossíntese , TransfecçãoRESUMO
BACKGROUND: There is a paucity of data on the use of etanercept in patients who have previously failed a different tumour necrosis factor (TNF) alpha antagonist. OBJECTIVES: To study etanercept in patients who did not achieve a satisfactory response to adalimumab or who lost their response to adalimumab or infliximab and to explore the role of anti-adalimumab and anti-infliximab antibodies in etanercept response. METHODS: Patients with psoriasis who did not achieve a satisfactory response to adalimumab or who lost their response to adalimumab or infliximab were included. All patients received etanercept 50 mg twice a week for 12 weeks followed by 50 mg once a week for 12 more weeks. Anti-infliximab and anti-adalimumab antibodies were measured at baseline. The primary objective was to study the efficacy of etanercept using the proportion of patients who achieved a physician global assessment (PGA) of 0 or 1. RESULTS: A total of 81 patients were included. The proportion of patients who achieved a PGA of 0 or 1 after 24 weeks of etanercept was 20.0% (95% CI 4.8-35.2%) for patients who had an unsatisfactory response to adalimumab, 35.1% (95% CI 19.0-51.3%) and 35.7% (95% CI 7.0-64.4%) for patients who lost their response to adalimumab and infliximab respectively. The proportion of patients who achieved a PGA of 0 or 1 at week 24 was numerically higher for patients who had anti-adalimumab or anti-infliximab antibodies (36.5%) as compared to those without (17.2%; P = 0.08). CONCLUSIONS: Etanercept can be effective in patients with psoriasis who failed a previous TNF alpha antagonist.
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Etanercepte/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab/imunologia , Adalimumab/uso terapêutico , Anticorpos/sangue , Feminino , Humanos , Infliximab/imunologia , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/imunologia , Falha de TratamentoRESUMO
PURPOSE: To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways. METHODS: A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks. ENDPOINTS: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF. RESULTS: Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14). CONCLUSIONS: NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.
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Acetilcisteína , Fibrose Cística , Inflamação , Pulmão , Estresse Oxidativo/efeitos dos fármacos , Acetilcisteína/administração & dosagem , Acetilcisteína/efeitos adversos , Administração Oral , Adolescente , Adulto , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Criança , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Fibrose Cística/metabolismo , Fibrose Cística/fisiopatologia , Método Duplo-Cego , Monitoramento de Medicamentos , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Elastase de Leucócito/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Testes de Função Respiratória/métodos , Escarro/efeitos dos fármacos , Escarro/metabolismo , Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Oral isotretinoin (ISO) is the gold standard for severe nodular acne. However, as some patients are unwilling or unable to take, or are intolerant to, ISO, other options are needed. OBJECTIVES: To compare efficacy and safety of oral ISO vs. doxycycline 200 mg plus adapalene 0·1%/benzoyl peroxide 2·5% gel (D+A/BPO) in severe nodular acne over 20 weeks. METHODS: This was a multicentre, randomized, controlled, noninferiority investigator-blinded study involving 266 subjects. RESULTS: D+A/BPO showed a significantly earlier onset of action in reducing nodules, papules/pustules and total lesions at week 2. ISO was superior in reducing nodules (95·6% vs. 88·7%), papules/pustules (95·2% vs. 79·6%) and total lesions (92·9% vs. 78·2%; all P < 0·01) at week 20. Half as many subjects for D+A/BPO compared with ISO had treatment-related, medically relevant adverse events (33 events in 18·0% of subjects vs. 73 in 33·8% of subjects, respectively). D+A/BPO was noninferior to ISO in the intent-to-treat population [95% confidence interval (CI) -2·7 to 20·8 (P = 0·13); 63·9% vs. 54·9% of subjects, respectively] and per-protocol population [95% CI 3·9-28·6 (P = 0·01); 74·3% vs. 58% of subjects, respectively), based on the composite efficacy/safety end point. CONCLUSIONS: D+A/BPO showed a favourable composite efficacy/safety profile compared with ISO. This combination is an alternative to ISO in patients intolerant to, or unable or unwilling to take, oral ISO, and is an option for treatment of severe nodular acne.
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Acne Vulgar/tratamento farmacológico , Peróxido de Benzoíla/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Doxiciclina/administração & dosagem , Isotretinoína/administração & dosagem , Naftalenos/administração & dosagem , Adapaleno , Administração Cutânea , Adolescente , Adulto , Peróxido de Benzoíla/efeitos adversos , Criança , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Doxiciclina/efeitos adversos , Quimioterapia Combinada , Feminino , Géis , Humanos , Isotretinoína/efeitos adversos , Masculino , Naftalenos/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Pruritus, or itch, is a common sensation that causes a person to want to scratch. It is a complex process that may negatively impact quality of life and commonly occurs with skin disorders such as atopic dermatitis and urticaria. It could also be a symptom related to an underlying disease process such as cholestasis or hyperthyroidism, or simply be caused by dry skin, especially in the cold, winter months. Therapy is often aimed at eliminating the underlying cause first, followed by the management of the itchy sensation. Treatment may include prescription and over-the-counter (OTC) medications, herbal remedies, hydrotherapy, phototherapy, and ultraviolet therapy. This overview provides information regarding the various management and treatment options for pruritus.
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Prurido/tratamento farmacológico , Corticosteroides/uso terapêutico , Anestésicos Locais/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Prurido/fisiopatologia , Terapia UltravioletaRESUMO
Atopic dermatitis (AD) is a chronically relapsing eczematous disorder of the skin that occurs in persons of all ages but is more common in children. AD is associated with other atopic diseases such as allergic rhinoconjuntivitis or bronchial asthma. Nearly 80% of children with AD eventually develop allergic rhinitis or asthma. AD can be classified as mixed (cases associated with respiratory allergies) and pure . Pure AD has intrinsic and extrinsic variants. In the extrinsic type, interleukin-4 is secreted by T-cells isolated from spontaneous lesions and skin-derived T-lymphocytes express more IL-13. Due to the different immunopathogenesis, it has been suggested that antileukotriene agents may be more successful in the treatment of the extrinsic subgroup. Leukotrienes (LTs) are a class of potent biological inflammatory mediators derived from arachidonic acid through the 5-lipoxygenase pathway. There is evidence of enhanced LT production in the pathogenesis of AD. Evidence in the literature provides a pathophysiological rationale for the use of cysLT receptor blockers in the treatment of AD. However, the exact mechanism of action of leukotriene receptor antagonists in AD is not known. In small clinical and case studies, montelukast was found to be a safe and effective alternative or steroid-sparing therapy in the management of patients with atopic dermatitis.