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Objective: Disease modifying therapies (DMTs) for multiple sclerosis (MS) aim to delay progression and reduce relapses. Evidence is limited on the comparative effectiveness of the oral DMTs fingolimod and teriflunomide. This study evaluated time to treatment failure among patients with MS who initiated fingolimod versus teriflunomide in real-world settings.Methods: The retrospective cohort included 18-64 year old patients diagnosed with MS who initiated fingolimod or teriflunomide during 12 September 2012 to 30 September 2015 within MarketScan Commercial and Medicare Claims. Patients were followed from treatment initiation (index date) until first treatment failure or censoring. Treatment failure was defined as the first occurrence of MS relapse (identified using a validated algorithm) or treatment discontinuation (≥60 day supply gap). Treatment failure was examined through Kaplan-Meier analysis and multivariable Cox regression adjusting for 1 year baseline factors (age, gender, plan type, region, index year, prior DMT use, baseline relapses, Charlson Comorbidity Index [CCI] and MS symptoms).Results: On average, patients treated with fingolimod (n = 2704) were younger (43.6 versus 49.8 years) with lower CCI (0.4 versus 0.7) and more relapses at baseline (0.46 versus 0.42) than those treated with teriflunomide (n = 1859). Median time to treatment failure was 19.5 months with fingolimod versus 9.6 months with teriflunomide (p < .001). After controlling key demographic and clinical characteristics through multivariable regression, fingolimod was associated with 38.9% lower hazards of treatment failure versus teriflunomide (adjusted hazard ratio = 0.611; 95% CI: 0.559-0.669; p < .001).Conclusions: In a large cohort of US adults with MS, controlling for key baseline characteristics, fingolimod was associated with significantly longer time to treatment failure and lower risk of treatment failure compared with teriflunomide. [ABSTRACT FROM AUTHOR]

Objective: Few studies have examined compliance to disease-modifying therapies (DMTs) for multiple sclerosis (MS) in minority populations. This study compared adherence, discontinuation, and persistence for fingolimod (FTY) and glatiramer acetate (GA) initiators among Hispanic and African American patients with MS.Methods: This retrospective claims data study examined Hispanic and African American adults with MS who initiated FTY or GA between September 1, 2010 and June 30, 2014. Outcomes (adherence, discontinuation, and persistence) were analyzed descriptively and with multivariable models, comparing FTY and GA cohorts within racial/ethnic groups. Adherence was assessed using medication possession ratio (MPR) and proportion of days covered (PDC).Results: There were 171 patients in the Hispanic group (62 FTY, 109 GA) and 210 in the African American group (71 FTY, 139 GA). A larger proportion of GA initiators than FTY initiators were treatment-naïve; other baseline characteristics were similar between cohorts. Hispanic FTY initiators had greater mean MPR, PDC, and persistence and less discontinuation than GA initiators. African American FTY initiators had greater mean PDC than GA initiators; other outcomes favored FTY but were not statistically significant. Multivariable analysis results were consistent with the unadjusted results, but differences between treatment cohorts were not statistically significant.Conclusions: Hispanic and African American patients with MS who initiated FTY had higher adherence than those who initiated GA, similar to the general MS population. These findings suggest that adherence should be considered in DMT selection, and racial/ethnic variations in MS disease course may not be primarily attributable to differences in DMT compliance. [ABSTRACT FROM AUTHOR]

Background: Psoriasis treatment involves topical medications, oral medications, phototherapy, and/or biologics. The treatments used depend on a myriad of factors that change over time. Objective: To characterise the frequency of and reasons for treatment changes in patients with moderate to severe psoriasis. Methods: A chart review examined treatment changes at 902 visits by 116 patients seen between January 1, 2010, and June 30, 2015, for moderate to severe psoriasis and the physicians’ justifications for those changes. ‘Treatment change’ was defined as switching between, adding, or removing medication classes or switching within the oral or biologic class. Results: There were 221 visits with treatment changes identified, and a change occurred every 4.1 visits. On average, there were 1.2 treatment changes per year. Patients treated for at least 1 year averaged 1 treatment change every 16 months. The most common type of change was from one biologic to another biologic (24.9%), followed by adding a nonbiologic to a biologic (18.6%). The most common reason for switching was poor control or flare of psoriasis. Affordability was a more common problem for biologics than for nonbiologic treatments. Conclusions: Biologic treatment options provide a major improvement over older systemic treatments, but patients still undergo frequent treatment changes to help control their disease. [ABSTRACT FROM AUTHOR]

Background: Psoriasis can greatly impact patients’ lives, influencing what clothing they wear and impairing their sexual functioning. Objective: To provide a detailed comparison of the impact of secukinumab vs. etanercept on enabling patients with psoriasis to have more normal lives with respect to daily activities (DA) (e.g. choosing clothing) and personal relationships (PR) (e.g. sexual functioning). Methods: Baseline to Week 52 ERASURE and FIXTURE data for secukinumab 300mg and etanercept were analyzed. Treatment differences in mean scores on the DA and PR subscales and items from the Dermatology Life Quality Index were compared. The proportions of subscale and item responders (score =0) were compared. Results: Subjects receiving secukinumab (n=572) achieved greater mean improvement in DA and items (q3 and q4) than subjects receiving etanercept (n=326; all p<.01 through Week 52). Subjects receiving secukinumab achieved greater mean improvement in PR and items (q8 and q9) than subjects receiving etanercept (subscale: p<.05 at Weeks 8 and 12). Response rates were significantly higher for secukinumab than for etanercept for DA (all p<.0001) and PR (all p<.05 except Weeks 4 and 36). Conclusions: Secukinumab 300 mg provides greater improvements and more effective relief from psoriasis impact on DA and PR than etanercept. [ABSTRACT FROM AUTHOR]

Background:Conventional measurements for assessing psoriasis treatment effects capture improvements at fixed, pre-specified timepoints, failing to account for cumulative clinical benefit over time. Objective:Explore the innovative concept of “cumulative clinical benefit” by examining the effect of secukinumab over 52 weeks in moderate-to-severe psoriasis patients. Methods:Cumulative clinical benefit was determined as the area-under-the-curve of the percentage of responders over 52 weeks (AUC0–52 wks), using pooled data from two phase III trials for patients receiving secukinumab (300 or 150 mg) or etanercept. Results:Normalized cumulative benefit with secukinumab 300 mg, secukinumab 150 mg, and etanercept was 74.2%, 63.2%, and 50.5%, respectively, for PASI 75; 58.0%, 42.5%, and 29.5%, respectively, for PASI 90; 32.3%, 18.8%, and 8.7%, respectively, for PASI 100; and 58.3%, 47.9%, and 38.3%, respectively, for DLQI 0/1. 52-week PASI 75 clinical benefit ratios for secukinumab 300 and 150 mg versus etanercept were 1.47 and 1.25, respectively; the ratio of the two secukinumab doses was 1.17, favoring 300 mg. Limitations:Post hocanalysis. Conclusion:Cumulative clinical benefit estimated by AUC0-52 wksis a novel measure for comparing psoriasis treatments. Secukinumab 300 mg provides greater cumulative clinical benefit than secukinumab 150 mg; both provide greater cumulative benefit than etanercept. [ABSTRACT FROM AUTHOR]

Background: Little is known about the longitudinal change in the quality of acute asthma care for hospitalized children and adults in the United States. We investigated whether the concordance of inpatient asthma care with the national guidelines improved over time, identified hospital characteristics predictive of guideline concordance, and determined whether guideline-concordant care is associated with a shorter hospital length of stay (LOS).Methods: This study was an analysis of data from two multicenter chart review studies of hospitalized patients aged 2 to 54 years with acute asthma during two time periods: 1999-2000 and 2012-2013. Outcomes were guideline concordance at the patient and hospital levels, and association of patient composite concordance with hospital LOS.Results: The analytic cohort for the comparison of guideline concordance comprised 1,634 patients: 834 patients from 1999-2000 vs 800 patients from 2012-2013. Over these 15 years, inpatient asthma care became more concordant at the hospital-level, with the mean composite score increasing from 74 to 82 (P < .001). However, during 2012-2013, wide variability in guideline concordance of acute asthma care remained across hospitals, with the greatest variation in provision of individualized written action plan at discharge (SD, 36). Guideline concordance was significantly lower in Midwestern and Southern hospitals compared with Northeastern hospitals. After adjusting for severity, patients who received care perfectly concordant with the guidelines had significantly shorter hospital LOS (-14% [95% CI, -23 to -4]; P = .009).Conclusions: Between 1999 and 2013, the guideline concordance of acute asthma care for hospitalized patients improved. However, interhospital variability remains substantial. Greater concordance with evidence-based guidelines was associated with a shorter hospital LOS. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the beneficial effects of statins use on asthma-related hospitalizations and emergency department (ED) visits. Topics include the use of the Medco Health Solutions National Integrated Database of the U.S. in the study, assessment of statin and asthma therapy through National Drug Codes for medications and the association of inhaled corticosteroid (ICS) with the use of statins, as of April 2014.

Objectives: The aim of this study was to explore factors that modify treatment effects of non-conventional biologics versus placebo in patients with psoriatic arthritis., Methods: A systematic literature review and meta-regression was conducted. The biologics included etanercept, infliximab, adalimumab, golimumab, certolizumab, ustekinumab, tocilizumab, anakinra, abatacept, rituximab, and secukinumab. Outcomes included American College of Rheumatology (ACR) 20 and 50, Psoriasis Area Severity Index (PASI) 75, and 36-Item Short Form Health Survey (SF-36) Physical and Mental Component Summaries (PCS and MCS)., Results: Twelve RCTs were eligible for meta-regression. Treatment effects for ACR-20 at 12 weeks were higher in trials with longer disease durations (OR=2.94), and lower in trials enrolling older patients (OR=0.48), and those recently published (OR=0.49). Treatment effects for ACR-50 at 12 weeks were higher in trials with more males (OR=2.27), but lower in trials with high prior anti-TNF use (OR=0.28) and recently published trials (OR=0.37). For PASI-75, trials with more male patients (24 weeks: OR=2.56), and with higher swollen and tender joint counts (12 weeks: OR=8.33; 24 weeks: OR=14.44) showed higher treatment effects, and trials with high prior anti-TNF use had lower effects (OR=0.41). Treatment effects for SF-36 PCS at 24 weeks were higher in trials with longer psoriasis disease durations (OR=2.95) and PsA disease durations (OR=4.76), and those published earlier (OR=4.19)., Conclusions: Our analyses show that differences in baseline characteristics may explain some of the differences in response to biologics versus placebo across different trials. Accounting for these factors in future studies will likely be important.

OBJECTIVE: To compare patients with psoriasis by cost level over 3 years.

METHODS: Psoriasis patients in a large US health plan in 2011-2013 were identified. Four groups were created by healthcare costs excluding biologics: patients having top 10% of costs in all 3 years (Top), top 10% in 2 of 3 years (High), bottom 90% in 2 of 3 years (Medium), and bottom 90% in all 3 years (Bottom). Comorbidities, utilization, and costs between groups were compared.

RESULTS: The study included 18,653 patients: 514 (3%), 805 (4%), 2,443 (13%), and 14,891 (80%) patients in the Top, High, Medium, and Bottom groups, respectively. Significantly more patients in the Top vs Bottom group had diabetes (31.1% vs 9.4%), cardiovascular disease (26.5% vs 4.3%), psoriatic arthritis (25.7% vs 10.7%), depression (27.8% vs 6.9%), and anxiety (22.0% vs 7.9%) in 2011 (all P less than 0.05). Patients in the Top group had more unique 2011 prescriptions (17.7 vs 6.6; P less than 0.001) than the Bottom group, but similar biologic use (22.4% vs 21.6%). Patients in the Top, High, Medium, and Bottom groups had mean 2011 total costs of $68,913, $40,575, $24,292, and $8,815, and contributed to 14%, 13%, 23%, and 51% of the overall costs, respectively. Mean total costs increased 14-18% over time for all groups. Although mean 2011 total costs for patients in the Top group were 7.8 times of those in the Bottom group, psoriasis-related costs were less disparate ($8,716 vs $4,541). Compared with patients in the Bottom group, those in the Top group were more likely to have any 2011 hospitalization (36.8% vs 2.6%; psoriasis-related: 11.1% vs 0.7%) or emergency visit (50.8% vs 20.8%; psoriasis-related: 3.9% vs 1.0%).

CONCLUSION: The costliest patients with psoriasis had significantly higher prevalence of comorbidities, prescription fills, inpatient and emergency utilization, but not biologic medication use or biologic costs.

J Drugs Dermatol. 2017;16(7):651-658.

Background: BEZ235 is a dual phosphatidylinositol 3-kinase (PI(3)K)/mammalian target of rapamycin (mTOR) inhibitor that is orally available and that has been shown to be effective in several malignancies in vitro. Recently, BEZ235 entered clinical trials for solid tumors. We aimed at investigating if BEZ235 is effective in lung cancer cell lines., Materials and Methods: The human lung cancer cell lines EPLC, HCC and H1339 were analysed by fluorescence in situ hybridization, gene sequencing and Western blot analysis. Cells were exposed to BEZ235 and/or cisplatin and the survival fraction was quantified., Results: In all cell lines, BEZ235 reduced pAkt and pS6 expression indicating interference with the epidermal growth factor (EGF) pathway. Furthermore, BEZ235 inhibited tumor cell growth and added to the effects of cisplatin. This was independent of EGFR amplification and EGFR, KRAS, PI3K and AKT mutation., Conclusion: The dual PI3K/mTOR inhibitor BEZ235 is effective in lung cancer cell lines and a promising compound to be tested in clinical phase I studies.