RESUMO
INTRODUCTION: Psoriatic disease is associated with considerable impairment of quality of life (QoL). The PROSE study (NCT02752776) investigated the impact of secukinumab treatment on patient-reported outcomes (PRO) in patients with moderate to severe psoriasis stratified by their treatment history. METHODS: PROSE was a prospective, non-randomised, multicentre study. Patients were categorized at baseline according to treatment history as naïve [naïve to any systemic therapy (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic (CS) therapy (N = 673)] and biologics [previously exposed to ≥1 biologic therapy (N = 324)]. QoL PROs, efficacy and safety of secukinumab 300 mg were assessed for a period of 52 weeks. RESULTS: The primary objective was met with 70.8% patients achieving a Dermatology Life Quality Index (DLQI) 0/1 response at Week 16 (naÏve, 74.7%; CS, 71.3%; biologic, 61.7%), with effects sustained up to Week 52. Mean Family DLQI (FDLQI) score decreased from 11.5 at baseline (naÏve, 11.3; CS, 11.4; biologic, 12.1) to 2.5 at Week 16 (naÏve, 2.5; CS, 2.3; biologic: 3.5). Substantial improvements in EuroQoL 5-Dimension Health Questionnaire, Numeric Rating Scale for pain, itching and scaling, Health Assessment Questionnaire-Disability Index, Treatment Satisfaction Questionnaire for Medication, and Patient Benefit Index were also observed at Week 16. The QoL gains were associated with substantial improvements in Psoriasis Area and Severity Index and Investigator Global Assessment mod 2011 0/1 response. No meaningful difference was observed in the efficacy or QoL improvements across patient subpopulations. All QoL and efficacy parameter improvements were sustained up to Week 52. Secukinumab treatment was well-tolerated, and no new safety signals were observed. CONCLUSION: Secukinumab treatment resulted in complete normalization of QoL in a substantial proportion of psoriasis patients, and their families, regardless of their prior treatment history.
Assuntos
Psoríase , Qualidade de Vida , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Secukinumab is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin-17A. OBJECTIVES: To assess the efficacy and safety of different maintenance dosing regimens of secukinumab 300 mg based on Psoriasis Area and Severity Index (PASI) response at week 24 in patients with moderate-to-severe plaque psoriasis. METHODS: OPTIMISE was a randomized, open-label, rater-blinded phase IIIb study. Patients (n = 1647) received secukinumab 300 mg at baseline; weeks 1, 2, 3 and 4; and every 4 weeks (q4w) to week 24. At week 24, PASI 90 responders (≥ 90% improvement in PASI; n = 1306) were randomized to secukinumab 300 mg q4w (n = 644) or q6w (n = 662) to week 52, and PASI ≥ 75 to < 90 responders (n = 206) were randomized to secukinumab 300 mg q4w (n = 114) or q2w (n = 92) to week 52. RESULTS: PASI 90 response was maintained at week 52 by 85·7% of patients with q4w dosing vs. 74·9% with q6w dosing (odds ratio 1·91, 95% confidence interval 1·44-2·55). The primary end point, noninferiority of q6w vs. q4w dosing, was not met. In PASI ≥ 75 to < 90 responders, the proportion of patients with PASI 90 response at week 52 was numerically higher in the q2w vs. the q4w group (57% vs. 46·5%, respectively, P = 0·10). Heavier patients (≥ 90 kg) demonstrated numerically higher PASI 90 response with the q2w (57·1%) vs. the q4w regimen (40%, P = 0·11). CONCLUSIONS: Standard q4w dosing of secukinumab 300 mg is the optimal dosing regimen to achieve and maintain clear or almost clear skin. Patients with body weight ≥ 90 kg not achieving PASI 90 at week 24 may benefit from the q2w dosing regimen. What's already known about this topic? Individual responses to biologics in patients with psoriasis vary considerably and there may be a need to individualize treatment. Dose optimization strategies of currently available biologic drugs have been investigated mainly in rheumatic disorders. Secukinumab has shown long-term PASI 90/100 responses (percentage improvement in Psoriasis Area and Severity Index) to year 5 in patients with moderate-to-severe plaque psoriasis when used at the dose of 300 mg every 4 weeks. What does this study add? Standard every 4 week (q4w) dosing of secukinumab 300 mg is the optimal regimen to achieve and maintain clear or almost clear skin at week 52; the majority of the patients (85·7%) maintain PASI 90 at week 52. Superiority of intensified (q2w) dosing over the q4w regimen could not be claimed. However, patients with a higher body weight (≥ 90 kg) not achieving PASI 90 response at week 24 may benefit from q2w dosing.
Assuntos
Anticorpos Monoclonais Humanizados , Psoríase , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Psoriatic disease is associated with considerable impairment of Quality of Life (QoL). The PROSE study (NCT02752776) examined the impact of secukinumab on patient-reported outcomes in patients with moderate-to-severe psoriasis (PsO) stratified by previous exposure to systemic treatment. METHODS: In this prospective, non-randomized, multicentre study, patients were categorized at baseline according to previous exposure to systemic treatment: naïve [naïve to any systemic treatment (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic therapy (N = 673)] and biologics [previously exposed to ≥1 biologic (N = 324)]. Baseline demographics including age, gender, race, body weight and body mass index, disease characteristics and patient-reported QoL outcomes [Dermatology Life Quality Index (DLQI), Family DLQI (F-DLQI)] of patients enrolled in the study are reported here. RESULTS: Baseline demographic characteristics were well balanced across the three subpopulations. Naïve patients had a shorter time since diagnosis (15.5 ± 12.1 years) compared with the conventional systemic (19.1 ± 12.5 years) and biologic patients (23.0 ± 12.5 years), and lower rates of psoriatic arthritis (6.6% vs. 17.4% and 27.8%, respectively). Metabolic syndrome (37.6-43.5%), obesity (16.9-19.1%), hyperlipidaemia (15.3-21.9%) and diabetes mellitus (6.8-14.2%) were reported at numerically higher rate in the biologic group. The mean PASI (19.7 ± 7.9), affected Body Surface Area (28.2 ± 15.3%) as well as the Investigator Global Assessment score (patients with score 4: 33.7%) indicated severe disease at baseline and were comparable for the three groups. QoL impairment was evident from mean DLQI (14.1 ± 7.1: naïve = 13.5 ± 6.8; conventional systemic = 14.3 ± 7.0; biologic = 14.8 ± 7.7) and mean F-DLQI (11.5 ± 7.0: naïve = 11.3 ± 7.1; conventional systemic = 11.4 ± 6.7; biologic = 12.1 ± 7.7) also indicated derangement of QoL of patients and their families. CONCLUSION: Patients naïve to systemic treatment had shorter disease journey compared with patients previously exposed to systemic treatments; despite this, the severe impact of disease on patient and family QoL outcomes can be as apparent in naïve patients as in systemically treated patients at baseline.
Assuntos
Artrite Psoriásica , Psoríase , Superfície Corporal , Humanos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-α2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600 mg once daily (QD), ALV 800 mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48 weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received ≥31 weeks of randomized treatment; patients completed 48 weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P ≤ 0.0131), with highest cEVR rate seen with ALV 400 mg BID (74% vs 36% with PR alone; P < 0.0001). Respective SVR12 rates (key secondary endpoint) were 65% vs 26% in prior relapsers, 63% vs 5% in partial responders and 68% vs 3% in null responders. In patients who received >40 weeks of randomized treatment, the SVR12 rate was 89% for ALV 400 mg BID vs 30% for PR alone (P = 0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400 mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents.
Assuntos
Antivirais/uso terapêutico , Ciclosporina/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Ciclosporina/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Placebos , Ribavirina/efeitos adversos , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
REFINE was a 12-month, prospective, open-label study in 356 patients receiving de novo liver transplantation for hepatitis C virus (HCV) cirrhosis, randomized to cyclosporine A (CsA) or tacrolimus with (i) no steroids, IL-2 receptor antibody induction and mycophenolic acid, or (ii) slow steroid tapering. The primary analysis population based on availability of liver biopsies comprised 165 patients (88 CsA, 77 tacrolimus). There was no difference in the primary endpoint, fibrosis stage ≥2 at 12 months, which occurred in 63/88 CsA-treated patients (71.6%) and 52/77 tacrolimus-treated patients (67.5%) (odds ratio [OR] 1.11; 95% CI 0.56, 2.21; p = 0.759). Similarly, no significant between-group difference occurred at month 24 (OR 1.15; 95% CI 0.47, 2.80; p = 0.767). Among steroid-free patients, fibrosis score ≥2 was significantly less frequent with CsA versus tacrolimus at month 12 (7/37 [18.9%] vs. 16/38 [42.1%]; p = 0.029). HCV viral load was similar in both the tacrolimus- and CsA-treated cohorts. Mean blood glucose was significantly higher with tacrolimus from day 15 onward. Biopsy-proven acute rejection, graft loss and death were similar. These results showed no differences in posttransplant HCV-induced liver fibrosis between patients treated with CsA or tacrolimus in steroid-containing regimens, whereas CsA in steroid-free protocols was associated with reduced severity of fibrosis progression at 1 year posttransplant.
Assuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Hepatite C/cirurgia , Imunossupressores/uso terapêutico , Cirrose Hepática/prevenção & controle , Transplante de Fígado , Tacrolimo/uso terapêutico , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. RESULTS: A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). CONCLUSION: Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA.
Assuntos
Ciclosporina , Psoríase , Estudos Transversais , Ciclosporina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Coração/imunologia , Imunossupressores/farmacologia , Octreotida/farmacologia , Tacrolimo/farmacologia , Animais , Quimioterapia Combinada , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Hiperplasia , Masculino , Ratos , Ratos Endogâmicos Lew , Transplante Heterotópico , Túnica Íntima/patologiaAssuntos
Imunossupressores/uso terapêutico , Intestino Delgado/transplante , Transplante de Fígado/imunologia , Ativação Linfocitária , Tacrolimo/uso terapêutico , Transplante Homólogo/imunologia , Animais , Azatioprina/uso terapêutico , Células Cultivadas , Citotoxicidade Imunológica , Quimioterapia Combinada , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Intestino Delgado/imunologia , Teste de Cultura Mista de Linfócitos , Esteroides/uso terapêutico , SuínosAssuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Transplante de Fígado/imunologia , Tacrolimo/uso terapêutico , Adulto , Bilirrubina/sangue , Criança , Pré-Escolar , Monitoramento de Medicamentos , Seguimentos , Hepatite C/fisiopatologia , Humanos , Pessoa de Meia-Idade , Recidiva , Reoperação , Tacrolimo/administração & dosagem , Tacrolimo/sangue , Falha de Tratamento , Resultado do TratamentoAssuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Linfócitos/imunologia , Octreotida/uso terapêutico , Transplante de Pele/imunologia , Tacrolimo/uso terapêutico , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Masculino , Octreotida/farmacologia , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Baço/imunologia , Tacrolimo/farmacologiaAssuntos
Ácido Hialurônico/metabolismo , Mucosa Intestinal/fisiologia , Mucosa Intestinal/transplante , Intestino Delgado/transplante , Transplante Homólogo/fisiologia , Animais , Feminino , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Ácido Hialurônico/análise , Imunossupressores/uso terapêutico , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Intestino Delgado/fisiologia , Transplante de Fígado/fisiologia , Valores de Referência , Suínos , Tacrolimo/uso terapêutico , Transplante Homólogo/patologiaAssuntos
Rejeição de Enxerto/epidemiologia , Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Tacrolimo/uso terapêutico , Administração Oral , Adulto , Azatioprina/uso terapêutico , Doenças Transmissíveis/epidemiologia , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Metilprednisolona/uso terapêutico , Muromonab-CD3/uso terapêutico , Complicações Pós-Operatórias , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Fatores de TempoAssuntos
Proteínas Inativadoras do Complemento/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Guanidinas/uso terapêutico , Transplante de Fígado/imunologia , Transplante Heterólogo/imunologia , Animais , Azatioprina/uso terapêutico , Benzamidinas , Proteínas Inativadoras do Complemento/administração & dosagem , Ciclosporina/uso terapêutico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Guanidinas/administração & dosagem , Imunoglobulina G/análise , Imunoglobulina M/análise , Imunossupressores/uso terapêutico , Infusões Intravenosas , Transplante de Fígado/patologia , Ovinos , Suínos , Fatores de Tempo , Transplante Heterólogo/patologiaAssuntos
Imunossupressores/uso terapêutico , Intestino Delgado/transplante , Transplante de Fígado/imunologia , Transplante Homólogo/imunologia , Animais , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Intestino Delgado/fisiologia , Transplante de Fígado/métodos , Transplante de Fígado/fisiologia , Complicações Pós-Operatórias , Esteroides/uso terapêutico , Suínos , Tacrolimo/uso terapêutico , Transplante Homólogo/métodos , Transplante Homólogo/fisiologiaAssuntos
Intestino Delgado/transplante , Transplante de Fígado , Complicações Pós-Operatórias , Transplante Homólogo , Animais , Antibacterianos , Ascite , Infecções Bacterianas/prevenção & controle , Diarreia , Quimioterapia Combinada/uso terapêutico , Feminino , Hidrotórax , Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Suínos , Transplante Homólogo/imunologiaAssuntos
Rejeição de Enxerto/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Intestino Delgado/transplante , Transplante de Fígado/imunologia , Linfócitos/imunologia , Transplante Homólogo/imunologia , Animais , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/imunologia , Transplante de Fígado/métodos , Linfonodos/imunologia , Ativação Linfocitária , Monitorização Imunológica/métodos , Suínos , Fatores de Tempo , Transplante Homólogo/métodosAssuntos
Imunossupressores/farmacocinética , Intestino Delgado/fisiologia , Intestino Delgado/transplante , Transplante de Fígado/fisiologia , Tacrolimo/farmacocinética , Transplante Homólogo/fisiologia , Administração Oral , Animais , Feminino , Gastrostomia , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Absorção Intestinal , Transplante de Fígado/imunologia , Suínos , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Fatores de Tempo , Transplante Homólogo/imunologiaRESUMO
This study was designed to investigate the prevalence of Cilia-associated respiratory (CAR) bacillus infection in rabbits reared for meat production in Italy and to correlate the presence of CAR bacillus with inflammatory lesions of the respiratory tract. Seventy health, 3-month-old, New Zealand White rabbits, raised in 10 different rabbitries in Northern Italy were randomly selected at slaughter. No gross lesions were found at necropsy in any rabbit. In each animal, the trachea and lungs were sampled, fixed in 10% formalin, embedded in paraffin and stained with the Warthin-Starry method to evaluate the presence of CAR bacillus, and with haematoxylin and eosin to evaluate the presence of inflammatory lesions. CAR bacillus was present in 50 out of 70 rabbits (71.4%) with a prevalence of the infection that varied from 30% to 100% in the seven rabbitries. CAR bacillus was present both in the trachea and bronchi in 23 cases (32.8%), only in the trachea in 24 cases (34.3%) and only in the bronchi in three cases (4.3%). Inflammatory lesions were found in the trachea (22 cases, 31.4%) and the bronchi (58 cases, 82.8). There was a strong, statically significant correlation between the presence of CAR bacillus in the bronchi and bronchial inflammatory lesions (P < 0.0001). This study indicates that CAR bacillus infection is widespread in conventionally reared rabbits in Italy and that a possible correlation exists between the presence of CAR bacillus and bronchial inflammatory lesions.