Predictors of response to etanercept-methotrexate treatment: a post hoc logistic regression analysis of a randomized, open-label study in Latin American patients with rheumatoid arthritis

Background: Determining potential predictors of clinical response would allow a more personalized rheumatoid arthritis (RA) treatment approach in heterogeneous populations such as Latin American (LA) patients. Methods: Post hoc analysis to identify baseline characteristics predictive of clinical remission in response to treatment with etanercept (ETN) plus methotrexate (MTX) in LA patients with moderate to severe MTX-resistant RA. We report data from the group of patients who received ETN 50 mg/week plus MTX (ETN + MTX, n = 281) in a clinical trial consisting of an initial 24-week open-label phase, followed by a 104-week extension. Remission was defined as 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) score  28.5 kg/m2 (OR 3.24), disease duration > 3.7 years (OR 2.22), ESR ≤ 42 mm/h (OR 2.72), PGA ≤ 6 (OR 3.21), tender joint count ≤ 14 (OR 2.25), and total HAQ score ≤ 1.6 (OR 2.86). At Week 128, age ≤ 42 years (OR 2.21), SF-36 Mental Health Scale score > 39.6 (OR 2.16), White race (OR 4.07), > 18 swollen joints (OR 2.11), and VAS Pain ≤ 41 (OR 6.05) at baseline were the best subset of significant predictors of remission. Conclusions In LA patients with RA, younger age, higher BMI, longer disease duration, higher SF-36 Mental Health Scale score, higher swollen joint count, and overall lower disease activity predicted clinical response to ETN + MTX therapy

Effect of etanercept therapy on psoriasis symptoms in patients from Latin America, Central Europe, and Asia : A subset analysis of the PRISTINE trial

Background: Psoriasis prevalence and characteristics in Asia, Central Europe, and Latin America have not been thoroughly investigated and there are no large trials for biologic treatments for patients from these regions. The goal of this analysis was to report clinical response to anti-tumor necrosis factor-alpha treatment in these patients. Methods: Patients from Argentina, Czech Republic, Hungary, Mexico, Taiwan, and Thailand (N = 171) were included in this subset analysis of the PRISTINE trial. Patients with stable moderate-to-severe plaque psoriasis were blinded and randomized to receive etanercept 50 mg once weekly (QW) or biweekly (BIW) for 12 weeks, followed by 12 weeks of open-label QW treatment with etanercept 50 mg through week 24 (QW/QW vs. BIW/QW). Concomitant methotrexate (≤20 mg/week) and mild topical corticosteroids or other agents were permitted at the physician's discretion, in accordance with therapeutic practice. Results: As early as week 8, 26.7 % in the etanercept QW group and 44.0 % in the BIW group achieved Psoriasis Area and Severity Index (PASI) 75. At weeks 12 and 24, respectively, PASI 75 increased to 39.5 % and 62.8 % in the QW/QW group and 66.7 % and 83.3 % in the BIW/QW group. PASI 75 was significantly different between treatment groups from week 8 through the end of study (p < 0.05). The Kaplan-Meier estimate of the proportions achieving PASI 75 in QW/QW and BIW/QW groups, respectively, was 27.4 % and 45.8 % through week 8; 41.9 % and 68.7 % through week 12; and 72.5 % and 95.2 % through week 24. Conclusions: Treatment with etanercept 50 mg provided rapid relief of psoriasis symptoms in patients from Asia, Central Europe, and Latin America. A more rapid response was observed in patients who received BIW treatment for the first 12 weeks which was sustained after reducing to QW dosing for the subsequent 12 weeks. Response rates were similar to those observed in the overall PRISTINE population. Trial registration: ClinicalTrials.gov identifier NCT00663052 © 2015 Kemeny et al

Long-term Etanercept Response for Patients with Radiographic Axial Spondyloarthritis Based on Achievement of Early, Intermediate, or Late Responses During Index Studies

Abstract Introduction Short-term placebo (PBO)- or active-controlled clinical studies have demonstrated that etanercept (ETN) is effective and well tolerated in patients with radiographic axial spondyloarthritis (r-axSpA) with long-term efficacy and safety continuing for up to 7 years after treatment start. Short-term randomized controlled trials (RCTs) have shown the efficacy of ETN after 12–24 weeks, with statistically significant improvements as early as week 2. This post hoc analysis investigated the timeframe (i.e., temporal responses) in which patients with r-axSpA achieved their first clinical response with ETN and how patients responded over a longer period according to different temporal responses in index studies. Methods Data were analyzed from three phase 3/4 PBO- or sulfasalazine-controlled RCTs of ETN for the treatment of r-axSpA (index studies). Long-term open-label extension (OLE) studies assessed how patients responded over a longer period according to different temporal responses (“Early,” “Intermediate,” “Late,” or “Non-response”) in their corresponding index studies. Results Within each index study, patient responses differed significantly between ETN and control arms for achievement of Assessment in SpondyloArthritis international Society (ASAS) 20 and other measures of treatment response. In general, the proportion of responders in the OLE studies was high for those with “Early” and “Intermediate” responses as defined in the index studies. Despite patients being considered non-responders in the index studies, a large proportion achieved response on continued treatment in the OLE studies over the longer term, including through 48 weeks. Conclusions Response in the index studies was maintained in the long term, and continued treatment was warranted in a large proportion of patients despite initial non-response. Absence of an early response in index studies did not predict non-response over the long term, and early response to treatment was not always a predictor for later response. Trial Registration NCT00421915; NCT00247962; NCT00356356; NCT00421980; NCT00410046

Comparison of Different Remission and Low Disease Definitions in Psoriatic Arthritis and Evaluation of Their Prognostic Value

OBJECTIVE: There is no agreement on the optimal definitions for assessing disease state in patients with psoriatic arthritis (PsA), and some of the commonly used definitions do not include assessment of skin lesions. We investigated the performance of various definitions in patients with PsA and psoriasis. METHODS: This was a posthoc analysis of data from the PRESTA study. The remission definitions analyzed were very low disease activity (VLDA) index, defined as 7/7 of the minimal disease activity (MDA) cutoffs; Disease Activity Index for PsA (DAPSA); and clinical (c-) DAPSA. The low disease activity (LDA) definitions analyzed were as follows: MDA defined as 5/7 cutoffs; MDA joint with both the tender joint count (TJC) and swollen joint count (SJC) cutoffs mandated; MDA skin where skin cutoff was mandated; MDA joint + skin where TJC, SJC, and skin cutoffs were mandated; DAPSA LDA; and cDAPSA LDA. RESULTS: At Week 24, the proportions of patients achieving VLDA, DAPSA, and cDAPSA remission were 10%, 35%, and 37%, respectively. Of the patients achieving DAPSA and cDAPSA remission, 55% and 56%, respectively, had Psoriasis Area and Severity Index \u3e 1. The proportions of patients achieving MDA 5/7, MDA skin, MDA joint, and MDA joint + skin were 44%, 19%, 36%, and 14%, respectively, versus 70% achieving DAPSA and cDAPSA LDA. Notable residual levels of psoriasis were observed in patients achieving the definitions that did not require skin disease control. CONCLUSION: VLDA and MDA definitions are more stringent than DAPSA and cDAPSA definitions for the assessment of PsA. The relevance of residual disease to patients, however, remains to be determined. [Clinical Trial registration: ClinicalTrials.gov NCT00245960]

Resilience as a predictor of treatment response in posttraumatic stress disorder patients treated with venlafaxine extended release or placebo

This post-hoc analysis evaluated resilience as a predictor of treatment response in patients with posttraumatic stress disorder (PTSD). Data were pooled from two randomized, double-blind studies conducted with adult outpatients treated with flexible doses of venlafaxine extended release (ER) 37.5 to 300 mg/day or placebo. The 17-item Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS-SX(17)) was the primary outcome measure. Baseline Connor-Davidson Resilience Scale (CD-RISC) scores for the 25-, 10-, and 2-item versions were used to predict changes in PTSD symptom severity at week 12 and symptomatic remission (CAPS-SX(17) ? 20). Analyses were conducted for the overall population and separately for the individual treatment groups. In total, pretreatment resilience predicted a positive treatment response. For the overall population, all versions of the CD-RISC predicted CAPS-SX(17) change scores and remission after controlling for variables such as treatment group and baseline symptom severity. For venlafaxine ER-treated patients, all versions of the CD-RISC were predictive of remission, but only the 10-item version was predictive of CAPS-SX(17) change score. Our results suggest that higher pretreatment resilience is generally associated with a positive treatment response. Future research may be warranted to explore the relationship between response to active treatment and the spectrum of resiliency

Additional file 2: Figure S1. of Predictors of remission with etanercept-methotrexate induction therapy and loss of remission with etanercept maintenance, reduction, or withdrawal in moderately active rheumatoid arthritis: results of the PRESERVE trial

Summary of patient disposition in the open-label and double-blind periods. CDAI Clinical Disease Activity Index, DAS28 Disease Activity Score based on a 28-joint count, ETN etanercept, LDA low disease activity, MTX methotrexate, QW once weekly, SDAI Simplified Disease Activity Index. (EPS 1688 kb

Dietary total fat intake and ischemic stroke risk: the Northern Manhattan Study

Dietary fat intake is associated with coronary heart disease risk, but the relationship between fat intake and ischemic stroke risk remains unclear. We hypothesized that total dietary fat as part of a Western diet is associated with increased risk of ischemic stroke. As part of the prospective Northern Manhattan Study, 3,183 stroke-free community residents over 40 years of age underwent evaluation of their medical history and had their diet assessed by a food-frequency survey. Cox proportional hazard models calculated risk of incident ischemic stroke. The mean age of participants was 69 years, 63% were women, 21% were white, 24% black and 52% Hispanic. During a mean of 5.5 years of follow-up, 142 ischemic strokes occurred. After adjusting for potential confounders, risk of ischemic stroke was higher in the upper quintile of total fat intake compared to the lowest quintile (HR 1.6, 95% CI 1.0-2.7). Total fat intake >65 g was associated with increased risk of ischemic stroke (HR 1.6, 95% CI 1.2-2.3). Risk was attenuated after controlling for caloric intake. The results suggest that increased daily total fat intake, especially above 65 g, significantly increases risk of ischemic stroke