A framework for longitudinal latent factor modelling of treatment response in clinical trials with applications to Psoriatic Arthritis and Rheumatoid Arthritis.

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.

Caffeine levels and dietary intake in smokers with schizophrenia and bipolar disorder.

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).

Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

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.

Comparison of remission and low disease activity states with DAPSA, MDA and VLDA in a clinical trial setting in psoriatic arthritis patients: 2-year results from the FUTURE 2 study.

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.

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease.

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.

Comparative effectiveness of secukinumab and etanercept in biologic-naïve patients with psoriatic arthritis assessed by matching-adjusted indirect comparison.

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.

Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies.

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.

Comparative effectiveness of secukinumab and adalimumab in ankylosing spondylitis as assessed by matching-adjusted indirect comparison.

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.

Secukinumab provides rapid and sustained pain relief in psoriatic arthritis over 2 years: results from the FUTURE 2 study.

Background: Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of secukinumab on patient-reported pain in PsA through 104 weeks of treatment.

Minimal Disease Activity Among Active Psoriatic Arthritis Patients Treated With Secukinumab: 2-Year Results From a Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase III Study.

Objective: To evaluate minimal disease activity (MDA) among psoriatic arthritis (PsA) patients receiving secukinumab through 2 years in the FUTURE 2 study.

Methods: Patients with active PsA were randomized to receive subcutaneous secukinumab 300, 150, or 75 mg or placebo. MDA was assessed in the overall population (anti-tumor necrosis factor [anti-TNF]-naive and inadequate responders [anti-TNF-IR]) and in patients stratified by prior anti-TNF exposure and by time since diagnosis at weeks 16, 24, 52, and 104.

Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis.

Introduction: Patients with rheumatoid arthritis (RA) are at an increased risk of malignancies compared with the general population. This has raised concerns regarding these patients, particularly with the widespread use of immunomodulating therapies, including biologic disease-modifying antirheumatic drugs (DMARDs). We performed a systematic literature review and analysis to quantify the incidence of malignancies in patients with RA and the general population to update previously published data.

Nicotine intake and smoking topography in smokers with bipolar disorder.

Objectives: Cigarette smoking behavior in bipolar disorder (BPD), including the effects of mood-stabilizing medications, has not been well characterized.

Methods: We compared serum nicotine, nicotine metabolite levels, and smoking topography in 75 smokers with BPD to 86 control smokers (CON). For some comparisons, an additional control group of 75 smokers with schizophrenia (SCZ) were included.

Rapid smoking may not be aversive in schizophrenia.

Introduction: Aversive smoking has been investigated as a smoking cessation technique that involves rapid smoking in a clinic or laboratory and typically involves (a) puffing every 6-10 s or (b) smoking 3 or more cigarettes sequentially in 8-20 min. Rapid smoking usually results in dizziness, sore throat, nausea, and other unpleasant feelings.

Methods: To explore rapid smoking, 161 smokers (75 with schizophrenia [SS]; 86 controls [CON]) were assessed in a single day (24 ± 2 hr), ad libitum smoking topography session using the Clinical Research Support System micro portable topography device.

Varenicline for tobacco dependence: panacea or plight?

Introduction: This review examines the postmarketing experience with varenicline, including case reports, newer clinical trials and secondary analyses of large clinical datasets.

Areas Covered: Varenicline has been shown to be an effective treatment in a broad range of tobacco users with medical, behavioral and diverse demographic characteristics. Recent studies finding excellent safety and efficacy in groups of smokers with diseases including chronic obstructive pulmonary disease are particularly encouraging and call for increased use of this medication for smoking cessation.

Shorter interpuff interval is associated with higher nicotine intake in smokers with schizophrenia.

Background: People with schizophrenia are frequent and heavy smokers.

Methods: The objective of this study was to measure serum nicotine levels and ad libitum smoking behavior for 24+2h using the CReSS micro topography device in 75 smokers with schizophrenia (SCZ) and compare these to 86 control smokers (CON) without mental illness. Mean values of repeatedly measured topography variables were compared using three-level nested linear models to adjust for between subject differences and the double nested data.

Lower task persistence in smokers with schizophrenia as compared to non-psychiatric control smokers.

One contributing factor to difficulty in quitting smoking may be task persistence, which can be viewed as a behavioral manifestation of distress tolerance, and describes the act of persisting in a difficult or effortful task. Task persistence was assessed in smokers with schizophrenia and schizoaffective disorder (SZ/SA; N = 71) and non-psychiatric controls (N = 78) before a quit attempt. These data support the hypothesis that smokers with SZ/SA display less task persistence than do non-psychiatric controls when persistence is measured via mirror tracing and a 2-item persistence measure.

A comprehensive model for mental health tobacco recovery in new jersey.

Despite the high prevalence of tobacco use, disproportionate tobacco consumption, and excess morbidity and mortality, smokers with mental illness have reduced access to tobacco dependence treatment across the health care spectrum. We have developed a comprehensive model for Mental Health Tobacco Recovery in New Jersey (MHTR-NJ) that has the overarching goal of improving tobacco cessation for smokers with serious mental illness. Important steps involve engaging patients, professionals and the community to increase understanding that addressing tobacco use is important.

Higher nicotine levels in schizophrenia compared with controls after smoking a single cigarette.

Introduction: The increase in blood nicotine after smoking a single cigarette is nicotine boost. We hypothesized that smokers with schizophrenia (SCZ) have a greater nicotine boost than controls without this disorder.

Methods: Twenty-one subjects (11 SCZ and 10 controls, CON) had repeated venous blood sampling before, during, and after smoking a single cigarette after 12-hr abstinence to measure nicotine concentrations.

Evaluation of the CHOICES program of peer-to-peer tobacco education and advocacy.

CHOICES is a consumer driven program for addressing tobacco in people with mental illness that employs mental health peer counselors. Since 2005, CHOICES has conducted over 298 community visits reaching more than 10,000 smokers with mental illness (about 2500/year). A telephone based outcome study was conducted in 102 outpatient smokers who received a CHOICES peer-to-peer session.

Comparison of two intensities of tobacco dependence counseling in schizophrenia and schizoaffective disorder.

Compared to the general population, smokers with schizophrenia (SCZ) have reduced success in quitting smoking with usual approaches. This study tested two manualized behavioral counseling approaches-Treatment of Addiction to Nicotine in Schizophrenia (TANS) or Medication Management (MM)-for smokers who were motivated to quit. Individual counseling sessions were provided by mental health clinicians in mental health settings, along with nicotine patch.