RESUMO
OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials. METHODS: Our framework composes probabilistic principal component analysis with a longitudinal linear mixed effects model, thereby enabling clinical interpretation of multivariate results, while handling data missing at random, and incorporating covariates and covariance structure in a computationally efficient and principled way. RESULTS: We illustrate our approach by applying it to four phase III clinical trials of secukinumab in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). We identify three clinically plausible latent factors that collectively explain 74.5% of empirical variation in the longitudinal patient database. We estimate longitudinal trajectories of these factors, thereby enabling joint characterisation of disease progression and drug effect. We perform benchmarking experiments demonstrating our method's competitive performance at estimating average treatment effects compared to existing statistical and machine learning methods, and showing that our modular approach leads to relatively computationally efficient model fitting. CONCLUSION: Our multivariate longitudinal framework has the potential to illuminate the properties of existing composite endpoint methods, and to enable the development of novel clinical endpoints that provide enhanced and complementary perspectives on treatment response.
Assuntos
Artrite Psoriásica , Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Estudos Longitudinais , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêutico , Análise de Componente Principal , Ensaios Clínicos como Assunto , Ensaios Clínicos Fase III como Assunto , Modelos EstatísticosRESUMO
Caffeine is one of the most widely used psychoactive drugs in the United States. High rates of caffeine use have been observed in adult smokers as well as those with serious mental illness. The current secondary analysis aimed to extend previous findings demonstrating high caffeine intake in schizophrenia by examining dietary intake of caffeine and serum caffeine levels in outpatient smokers with schizophrenia (SCZ), bipolar disorder (BP) and control smokers with no psychiatric diagnoses (CON). Two hundred forty-eight adult smokers (SCZ=80; BP=80; CON=88) were included in the current study. Adult smokers with schizophrenia, bipolar disorder, and no psychiatric diagnoses were 40.85 (SD = 11.90) years old on average and all participants were current smokers (â¼20 cigarettes per day). Twenty-four hour self-reported caffeine intake (in mg) was highest among individuals with bipolar disorder (median=195.3), followed by adults with schizophrenia (median=155.0) and controls (median=131.7). Participants with bipolar disorder also had the highest serum caffeine levels (in ng/ml; median=1725), followed by those with schizophrenia (median=1194) and controls (median=613.2). These results provide additional evidence of high caffeine intake among adults with schizophrenia and extend findings by identifying even higher rates of caffeine use in those with bipolar disorder. The current study suggests that caffeine intake is higher among subgroups of patients with serious mental illness.
Assuntos
Transtorno Bipolar , Esquizofrenia , Adulto , Humanos , Estados Unidos , Criança , Esquizofrenia/diagnóstico , Cafeína , Transtorno Bipolar/psicologia , Fumar/psicologia , FumantesRESUMO
Tunneled catheter insertion is a routine procedure undertaken by nephrologists world over. However, the presence of a venous anomaly can always test one's skills and can give them anxious moments. Persistent left superior vena cava (SVC) is the most common venous anomaly. We share our experience of successfully placing a hemodialysis central venous catheter in a very rare congenital anomaly wherein patient had persistent left SVC with agenesis of the right SVC.
Assuntos
Cateteres Venosos Centrais , Doenças Vasculares , Cateterismo , Cateteres Venosos Centrais/efeitos adversos , Humanos , Nefrologistas , Diálise Renal , Veia Cava Superior/anormalidadesRESUMO
Although pica is commonly associated with nutritional deficiencies, it is also observed in psychiatric disorders such as obsessive-compulsive disorder and less commonly in schizophrenia. We describe a case of pica in a 34-year-old male with decompensated schizophrenia. Emergency medical services brought the patient from a state facility as he was scavenging and eating foreign objects. Upon initial evaluation, no notable nutritional deficiencies were noted. After surgical removal of foreign objects, he was started on antipsychotics. His pica was determined to be due to his active psychosis involving delusions, disorganized thought processes, and loosening of associations. His psychosis improved on paliperidone intramuscular injection and oral olanzapine, which coincided with reduction and resolution of pica. Our case highlights the need to understand further the exact psychopathology of pica that may not be limited to nutritional deficiencies.
RESUMO
Few case reports of catatonia associated with cannabis use are reported. Here, we describe a case of a 35-year-old African American male who developed malignant catatonia following heavy cannabis use. The patient was brought to the emergency department (ED) for altered mental status, hypertension, and erratic behavior. Before his ED presentation, he was smoking cannabis in heavy amounts, confirmed by positive urine toxicology in ED. Initial lab results showed leukocytosis, elevated creatine phosphokinase (CPK) levels. Head CT scans without contrast, including cerebrospinal fluid (CSF) analysis, were nonsignificant. In ED, the patient was agitated, combative, mute, and rigid. He was sedated using 2 mg of intramuscular (IM) midazolam. Psychiatric consultation services suspected catatonia, and the patient scored 12 points on Bush-Francis Catatonia Rating Scale (BFCRS). Although the patient's symptoms responded to 2 mg of IM lorazepam, the patient later relapsed, became tachycardic with blood pressure fluctuations, and his repeat BFCRS score was 18. At this point, the patient was diagnosed as having malignant catatonia, and his lorazepam dosage was increased up to 6 mg IM per day. After a few days of waxing and waning of his symptoms, he finally started to show constant improvement and gradually reduced his symptoms. Our case highlights the first-ever reported case of malignant catatonia associated with cannabis use.
RESUMO
BACKGROUND/OBJECTIVE: Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. METHODS: Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. RESULTS: Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. CONCLUSIONS: Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.
Assuntos
Espondilite Anquilosante , Inibidores do Fator de Necrose Tumoral , Fadiga/diagnóstico , Fadiga/epidemiologia , Fadiga/etiologia , Humanos , Dor , Qualidade de Vida , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico , Inquéritos e QuestionáriosAssuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Transplante de Rim/efeitos adversos , Trombocitopenia/induzido quimicamente , Adulto , Benzimidazóis/efeitos adversos , Humanos , Masculino , Oxidiazóis/efeitos adversos , Ramipril/efeitos adversosRESUMO
In the original publication of the article, while submitting the case report.
RESUMO
BACKGROUND/OBJECTIVE: The incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi). METHODS: Data from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire. RESULTS: 640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all p<0.0001), with HRQoL and WPAI measures considerably worse in patients with moderate to severe pain or fatigue than those with low pain or fatigue. CONCLUSIONS: Despite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies.
Assuntos
Artrite Psoriásica/tratamento farmacológico , Fadiga/epidemiologia , Dor/epidemiologia , Qualidade de Vida/psicologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Artrite Psoriásica/fisiopatologia , Artrite Psoriásica/psicologia , Avaliação da Deficiência , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Avaliação da Capacidade de TrabalhoRESUMO
OBJECTIVES: Remission (REM) or low disease activity (LDA) states were compared in a clinical trial setting of the FUTURE 2 study (NCT01752634) using Disease Activity Index for Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) composite indices in secukinumab treated PsA patients. METHODS: The proportion of patients reaching DAPSA-REM (cut-off ≤4) or REM+LDA (≤14), and very low disease activity (VLDA; achieving 7/7 criteria) or MDA (≥5/7), were compared in the overall population, by prior use of anti-TNF therapy, and by time since diagnosis using as observed data. The proportion of patients who met individual core component and other variables of interest were also computed to assess residual disease activity in DAPSA-REM/REM+LDA states and VLDA/MDA responses. The relationship between DAPSA/MDA and patient reported outcomes (PROs), including health-related quality of life, physical function, and fatigue were assessed using mixed model for repeated measures. RESULTS: More patients could achieve DAPSA-REM or DAPSA-REM+LDA status than VLDA or MDA responses, respectively, at all the time points in the overall population, irrespective of antiâTNF status and time since diagnosis. Higher proportion of patients reaching DAPSA-REM or VLDA achieved more thresholds of core components (joints, pain, patient and physician global assessments, and function) than DAPSA-REM+LDA or MDA over Week 104. There were differences with numerically higher proportion of patients achieving patient global assessment ≤10 mm and ≤20 mm, and physician global assessment ≤10 mm with MDA than with DAPSA-REM+LDA, and patient pain VAS ≤15 mm, PASI ≤1, HAQ ≤0.5 with VLDA or MDA than with DAPSA-REM or DAPSA-REM+LDA, respectively, through 104 weeks. Improvements in PROs were significantly better for patients in DAPSA-REM+LDA versus DAPSA-moderate+high disease activity status, and for MDA responders versus non-responders. CONCLUSION: These analysis add to the evidence that both DAPSA and MDA composite index measures can be used for evaluation of the status and treatment response utilizing a treat to target approach in PsA patients in a clinical trial setting and improve patient health related outcomes. FUNDING: The study and analysis was funded by Novartis Pharma AG, Basel, Switzerland.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Indução de Remissão/métodos , Artrite Psoriásica/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Qualidade de VidaRESUMO
BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy. (Funded by Novartis; REACH2 ClinicalTrials.gov number, NCT02913261.).
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Pirazóis/uso terapêutico , Transplante de Células-Tronco/efeitos adversos , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Feminino , Glucocorticoides/uso terapêutico , Humanos , Inibidores de Janus Quinases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrilas , Pirazóis/efeitos adversos , Pirimidinas , Trombocitopenia/induzido quimicamente , Transplante Homólogo , Adulto JovemRESUMO
Membranous nephropathy is known to be associated with number of autoimmune diseases. Occurrence of PLA2R positive membranous nephropathy with sjogren's syndrome and chronic inflammatory demyelinating neuropathy (CIDP) is quite rare. Role of PLA2R antigen in autoimmune diseases like sjogren's syndrome and CIDP is largely unknown. Choice and initiation of immunosuppression if required may also be governed by the presence of other autoimmune diseases along with PLA2R positive membranous nephropathy.
RESUMO
Post transplant lymphoproliferative disorder (PTLD) is a rare complication after kidney transplantation. Graft dysfunction is often encountered during the course of the treatment of PTLD, at times leading to need for retransplantation. We describe here the case of a young boy who underwent retransplantation after treatment of early Epstein Barr virus (EBV) related post transplant lymphoproliferative disorder. Our case highlights the various factors needing deliberation before retransplantation including time from remission of PTLD, EBV serostatus and choice of induction and maintenance immunosuppression agents.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Disfunção Primária do Enxerto/etiologia , Retratamento/métodos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Criança , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/virologia , Masculino , Complicações Pós-Operatórias , Indução de Remissão , Resultado do Tratamento , Valaciclovir/administração & dosagem , Valaciclovir/uso terapêuticoRESUMO
OBJECTIVE: Matching-adjusted indirect comparison (MAIC) can be used to assess the comparative effectiveness of two treatments indirectly using data from randomized placebo-controlled trials. This MAIC assessed the comparative effectiveness of secukinumab (an anti-interleukin-17A) and etanercept (a tumor necrosis factor inhibitor) in a target population of biologic-naïve patients with psoriatic arthritis (PsA). METHODS: Individual patient data pooled from FUTURE 2 (NCT01752634), FUTURE 3 (NCT01989468), and FUTURE 5 (NCT02404350) (secukinumab: 150 mg, n=458 and 300 mg, n=461) were matched to data from the population in the NCT00317499 trial (etanercept 25 mg, n=101) using MAIC methodology, by adjusting for clinical and demographic baseline characteristics. Recalculated outcomes from FUTURE 2, 3, and 5 (150 mg, effective sample size (ESS) post-matching=104; 300 mg, ESS=75; and placebo, ESS=159) were compared with the NCT00317499 trial. Pairwise comparisons using odds ratios (ORs) were performed for the American College of Rheumatology (ACR) 20, 50, and 70 response criteria at week 12 (placebo-adjusted) and week 24 (non-placebo-adjusted). RESULTS: At week 12, there were no significant differences in ACR responses between secukinumab and etanercept. There was no significant difference between secukinumab 150 mg and etanercept at week 24 with respect to ACR 20 and 50 response rates; however, ACR 70 response rates were higher for secukinumab 150 mg (OR (95% confidence interval (CI)): 4.48 (2.01-9.99), p<0.001). ACR 20, 50, and 70 response rates were higher with secukinumab 300 mg than with etanercept at this time point (OR (95% CI): ACR 20, 3.28 (1.69-6.38), p<0.001; ACR 50, 1.90 (1.04-3.50), p=0.038; and ACR 70, 3.56 (1.51-8.40), p=0.004). CONCLUSION: In this MAIC, secukinumab was associated with higher ACR 20 and 50 (secukinumab 300 mg) and 70 (secukinumab 150 mg and 300 mg) response rates at week 24 than etanercept in biologic-naïve patients with active PsA, whereas no significant difference was observed in the short-term at week 12.
RESUMO
Aim: To compare secukinumab with infliximab in biologic-naive patients with psoriatic arthritis using matching-adjusted indirect comparison. Patients & methods: Individual patient baseline data for secukinumab were matched to published aggregate data for infliximab by key baseline characteristics, with matching weights determined by logistic regression, and used to recalculate American College of Rheumatology (ACR) responses for secukinumab, for comparison with infliximab. Results: There were no differences in outcomes between secukinumab and infliximab at weeks 6/8 and 14/16. At weeks 24 and 54/52, ACR 20 responses were higher with secukinumab 150 mg than infliximab. At week 54/52, ACR 20/50 responses were higher for secukinumab 300 mg than infliximab. Conclusion: In the mid to long term, patients receiving secukinumab were more likely to achieve ACR 20/50 responses than those receiving infliximab.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Infliximab/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Produtos Biológicos , Pesquisa Comparativa da Efetividade , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate improvement in pain and fatigue in ankylosing spondylitis (AS) patients treated with secukinumab over 2 years (MEASURE 2 study). METHODS: Patients with active AS were randomised to receive secukinumab 150 mg, 75 mg, or placebo weekly until Week 4, and every 4 weeks thereafter. This post hoc analysis included assessment of spinal and nocturnal back pain, FACIT-Fatigue, and association between pain and either FACIT-Fatigue or ASQoL item 5 (sleep quality) for the approved secukinumab 150 mg dose in the overall population, and stratified by baseline high-sensitivity C-reactive protein (hsCRP) levels (normal [<5 mg/L] or elevated [≥5 mg/L]) or prior TNF inhibitor therapy status (TNFi-naïve or inadequate response [TNFi-IR]). RESULTS: Secukinumab-treated patients reported rapid improvement in pain and fatigue scores in overall population by Weeks 1 and 4, respectively; this trend of improvement was also observed irrespective of baseline hsCRP levels or prior TNFi therapy. Mean change at Week 16 in spinal/nocturnal pain (secukinumab vs. placebo) for the subgroups were -34.6/-30.2 vs. -16.6/-10.0, p<0.05/0.01 (normal hsCRP); -26.7/-31.6 vs. -7.8/-9.3, p<0.001/0.0001 (elevated hsCRP); -33.2/-35.4 vs. -13.2/-14.9, both p<0.0001 (TNFi-naïve); and -22.5/-22.8 vs. -9.4/-4.0, p=0.06/p<0.01 (TNFi-IR). FACIT-Fatigue was 7.1 vs. 3.3, p=0.15 (normal hsCRP); 8.7 vs. 3.6, p<0.05 (elevated hsCRP); 10.0 vs. 5.2, p<0.05 (TNFi-naïve); and 5.7 vs. 0.5, p=0.06 (TNFi-IR). These improvements were sustained or further improved through Week 104. CONCLUSIONS: Secukinumab provides rapid and sustained relief of pain and fatigue over 2 years in patients with AS regardless of baseline hsCRP levels and prior TNFi therapy.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Proteína C-Reativa/metabolismo , Espondilite Anquilosante , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Fadiga/tratamento farmacológico , Humanos , Dor/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Inibidores do Fator de Necrose TumoralRESUMO
OBJECTIVE: To evaluate the magnitude of response to secukinumab treatment over 3 years in patients with ankylosing spondylitis (AS) grouped by baseline C-reactive protein (CRP) levels in a pooled study of two pivotal phase III studies: MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375). METHODS: This post hoc analysis pooled data from all patients with available baseline CRP in the two studies who received subcutaneous secukinumab 150 mg (approved dose; N=197) or placebo (N=195). Assessed efficacy endpoints included Assessments of SpondyloArthritis international Society (ASAS)20/40, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, AS Disease Activity Score inactive disease and ASAS partial remission among patients grouped by baseline CRP based on central laboratory cut-off <5 mg/L (normal) or ≥5 mg/L (elevated) and a cut-off <10 mg/L or ≥10 mg/L. RESULTS: At baseline, 36.5% (143/392) patients had normal and 63.5% (249/392) had elevated CRP. At week 16, ASAS20/40 response rates were higher for secukinumab versus placebo in normal (56.9%/34.7% vs 28.2%/7.0%; p<0.01/p<0.001) and in elevated (63.2%/42.4% vs 29.0%/15.3%; both p<0.0001) CRP groups. Improvement was reported for all outcomes (p<0.05) in both groups, except for ASAS partial remission in the normal CRP group, where a numerical difference 12.5% vs 2.8%, p=0.07) was observed. Similar trends of improvement were observed in the <10 and ≥10 mg/L groups across all efficacy outcomes at week 16. Treatment responses to secukinumab in all CRP groups further improved over 156 weeks. CONCLUSION: Secukinumab 150 mg demonstrated rapid and sustained efficacy in patients with AS irrespective of baseline CRP, with greater magnitude of response in patients with more elevated CRP.
RESUMO
OBJECTIVE: Matching-adjusted indirect comparison was used to assess the comparative effectiveness of secukinumab 150 mg and adalimumab 40 mg in biologic-naïve patients with ankylosing spondylitis (AS) for up to 1 year. METHODS: Pooled individual patient data from the secukinumab arms of MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375) trials (n=197) were matched against the ATLAS (NCT00085644) adalimumab population (n=208). Logistic regression analysis was used to determined weights to match for age, sex, Bath AS Functional Index, C-reactive protein levels, and previous tumor necrosis factor inhibitor therapy. Recalculated Assessment of SpondyloArthritis International Society (ASAS) 20 and 40 responses at weeks 8, 12, 16, 24, and 52 from MEASURE 1/2 (effective sample size=120) were compared with those of ATLAS. Anchored (placebo-adjusted) comparisons were possible until week 12, and unanchored (non-placebo-adjusted) comparisons were necessary thereafter. RESULTS: For placebo-anchored ASAS 20 and 40 comparisons up to week 12, there were no differences between secukinumab and adalimumab. For unanchored comparisons at week 16, ASAS 20 was higher for secukinumab [odds ratio 1.60 (95% confidence interval, 1.01-2.54); p=0.047]; at week 24, ASAS 20 and 40 were higher for secukinumab [1.76 (1.11-2.79); p=0.017 and 1.79 (1.14-2.82); p=0.012, respectively]; and at week 52, ASAS 40 was higher for secukinumab [1.54 (1.06-2.23); p=0.023] than for adalimumab. CONCLUSION: There were no differences observed in placebo-adjusted ASAS 20 and 40 responses up to 12 weeks between secukinumab- and adalimumab-treated patients with ankylosing spondylitis. After week 12, secukinumab demonstrated signs of greater improvement in non-placebo-adjusted ASAS 20 and 40 responses than adalimumab.
RESUMO
AIM: A network meta-analysis using randomized controlled trial data compared psoriatic arthritis (PsA) outcomes (American College of Rheumatology [ACR], Psoriasis Area Severity Index [PASI] and Psoriatic Arthritis Response Criteria [PsARC] response rates) at 12-16 weeks for secukinumab, adalimumab, apremilast, certolizumab, etanercept, golimumab, infliximab and ustekinumab. PATIENTS & METHODS: Trials were identified by systematic review. Separate networks were developed for the full-study populations, biologic-naive patients and biologic-experienced patients. RESULTS: In the full populations, secukinumab, adalimumab, golimumab and infliximab demonstrated the highest ACR response rates. Secukinumab and infliximab demonstrated the highest PASI response rates, and infliximab and etanercept demonstrated the highest PsARC response rates. CONCLUSION: In the full populations, secukinumab demonstrated good efficacy across all outcomes. All treatments for active PsA included in this comprehensive network meta-analysis demonstrated superiority to placebo.