Research Spotlight

Posted September 15th 2016

Efficacy of Secukinumab on Moderate-to-severe Plaque Psoriasis Affecting Different Body Regions: a Pooled Analysis of Four Phase 3 Studies.

Alan M. Menter M.D.

Alan M. Menter M.D.

Menter, A., J. C. Cather, M. Jarratt, X. Meng, A. Guana and J. Nyirady (2016). “Efficacy of secukinumab on moderate-to-severe plaque psoriasis affecting different body regions: A pooled analysis of four phase 3 studies.” Dermatol Ther (Heidelb): 2016 Aug [Epub ahead of print].

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The impact of psoriasis varies with the body region affected. In addition, patients have different perceptions of disease improvement and treatment satisfaction based on the location of skin clearance with treatment. The monoclonal antibody secukinumab selectively targets interleukin-17A-a central cytokine of psoriasis-and provides rapid and sustained clearance for moderate-to-severe psoriasis affecting all body regions. The objective of this study was to evaluate the efficacy of secukinumab on moderate-to-severe psoriasis affecting the trunk, upper limbs, and lower limbs. METHODS: Data were pooled from four phase 3 studies. To be included in the analysis for each body region, patients were required to have a Psoriasis Area and Severity Index (PASI) score >/=12 for that body region and psoriasis covering >/=10% of the surface area of that region. Secukinumab was administered at Baseline, Weeks 1, 2 and 3, and then every 4 weeks from Week 4 to 48. RESULTS: Across the trunk, upper limbs, and lower limbs, initial PASI subscore responses were sustained to Week 52. At Week 52, trunk (T) PASI 90/100 responses were achieved by 78.4%/71.1% of patients receiving secukinumab 300 mg, respectively, and by 66.3%/56.9% of patients receiving secukinumab 150 mg, respectively. At Week 52, upper limb (UL) PASI 90/100 responses were achieved by 67.3%/59.1% of patients receiving secukinumab 300 mg, respectively, and by 50.3%/43.3% of patients receiving secukinumab 150 mg, respectively. At Week 52, lower limb (LL) PASI 90/100 responses were achieved by 63.9%/55.3% of patients receiving secukinumab 300 mg, respectively, and by 45.1%/36.4% of patients receiving secukinumab 150 mg, respectively. A 50% reduction in mean PASI subscore occurred after 2.8, 2.9, and 3.4 weeks with secukinumab 300 mg on the trunk, upper limbs, and lower limbs, respectively. CONCLUSION: Secukinumab provided robust and sustained efficacy for moderate-to-severe psoriasis affecting the trunk, upper limbs, and lower limbs.


Posted September 15th 2016

Impact of spine surgery complications on costs associated with management of adult spinal deformity.

Richard Hostin M.D.

Richard Hostin M.D.

Yeramaneni, S., C. Robinson and R. Hostin (2016). “Impact of spine surgery complications on costs associated with management of adult spinal deformity.” Curr Rev Musculoskelet Med 9(3): 327-332.

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A better understanding of the consequences of spine surgery complications is warranted to optimize patient-reported outcomes and contain the rising health care costs associated with the management of adult spinal deformity (ASD). We systematically searched PubMed and Scopus databases using keywords “adult spinal deformity surgery,” “complications,” and “cost” for published studies on costs of complications associated with spinal surgery, with a particular emphasis on ASD and scoliosis. In the 17 articles reviewed, we identified 355,354 patients with 11,148 reported complications. Infection was the most commonly reported complication, with an average treatment cost ranging from $15,817 to $38,701. Hospital costs for patients with deep venous thrombosis, pulmonary thromboembolism, and surgical site infection were 2.3 to 3.1 times greater than for patients without those complications. An effort to collect and characterize data on cost of complications is encouraged, which may help health care providers to identify potential resources to limit complications and overall costs.


Posted September 15th 2016

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA.

Milton Packer M.D.

Milton Packer M.D.

Packer, M. (2016). “Kicking the tyres of a heart failure trial: Physician response to the approval of sacubitril/valsartan in the USA.” Eur J Heart Fail: 2016 Aug [Epub ahead of print].

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Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition. The totality of evidence indicates that the PARADIGM-HF trial used an appropriate comparator; enrolled patients typical of those seen in the community with mild to moderate symptoms; yielded highly persuasive and replicable results; and demonstrated benefits that are applicable to patients taking subtarget doses of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the established advantages of sacubitril/valsartan on cardiovascular death and disease progression outweighed hypothetical uncertainties about the long-term effects of neprilysin inhibition in patients who might not have survived without the drug. Accordingly, both the new US and European Society of Cardiology heart failure guidelines recommend sacubitril/valsartan as the preferred approach to inhibiting the renin-angiotensin system in patients with chronic heart failure who are currently receiving an ACE inhibitor or ARB.


Posted September 15th 2016

Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer.

Ajay Goel Ph.D.

Ajay Goel Ph.D.

Shi, C., Y. Yang, Y. Xia, Y. Okugawa, J. Yang, Y. Liang, H. Chen, P. Zhang, F. Wang, H. Han, W. Wu, R. Gao, C. Gasche, H. Qin, Y. Ma and A. Goel (2016). “Novel evidence for an oncogenic role of microrna-21 in colitis-associated colorectal cancer.” Gut 65(9): 1470-1481.

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OBJECTIVE: miR-21 was found to be overexpressed in the colon tissues and serum of patients with UC and colorectal cancer (CRC); however, the exact roles of miR-21 in colitis-associated CRC remain unclear. The aim of our study was to investigate the biological mechanisms of miR-21 in colitis-associated colon cancer (CAC). DESIGN: miR-21 expression was examined in the tumours of 62 patients with CRC from China and 37 colitis-associated neoplastic tissues from Japan and Austria. The biological functions of miR-21 were studied using a series of in vitro, in vivo and clinical approaches. RESULTS: miR-21 levels were markedly upregulated in the tumours of 62 patients with CRC, 22 patients with CAC, and in a mouse model of CAC. Following azoxymethane and dextran sulfate sodium intervention, miR-21-knockout mice showed reduced expression of proinflammatory and procarcinogenic cytokines (interleukin (IL) 6, IL-23, IL-17A and IL-21) and a decrease in the size and number of tumours compared with the control mouse group. The absence of miR-21 resulted in the reduced expression of Ki67 and the attenuated proliferation of tumour cells with a simultaneous increase in E-cadherin and decrease in beta-catenin and SOX9 in the tumours of CAC mice. Furthermore, the absence of miR-21 increased the expression of its target gene PDCD4 and subsequently modulated nuclear factor (NF)-kappaB activation. Meanwhile, miR-21 loss reduced STAT3 and Bcl-2 activation, causing an increase in the apoptosis of tumour cells in CAC mice. CONCLUSIONS: These observations provide novel evidence for miR-21 blockade to be a key strategy in reducing CAC.


Posted September 15th 2016

Comparative efficacy of coronary artery bypass surgery vs. percutaneous coronary intervention in patients with diabetes and multivessel coronary artery disease with or without chronic kidney disease.

Michael J. Mack M.D.

Michael J. Mack M.D.

Baber, U., M. E. Farkouh, Y. Arbel, P. Muntner, G. Dangas, M. J. Mack, T. H. Hamza, R. Mehran and V. Fuster (2016). “Comparative efficacy of coronary artery bypass surgery vs. Percutaneous coronary intervention in patients with diabetes and multivessel coronary artery disease with or without chronic kidney disease.” Eur Heart J: 2016 Aug [Epub ahead of print].

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BACKGROUND: The optimal method of coronary revascularization among patients with diabetes mellitus (DM) and multivessel coronary artery disease (CAD) complicated by chronic kidney disease (CKD) remains unknown. PURPOSE: To examine the impact of coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) on cardiovascular outcomes in patients with diabetes with and without CKD. METHODS: We conducted an ‘as-treated’ subgroup analysis of the FREEDOM trial to examine the therapeutic efficacy of CABG vs. PCI among patients with DM stratified by the presence (n = 451) or absence (n = 1392) of CKD. We defined CKD as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Baseline characteristics and clinical outcomes were compared between PCI and CABG groups within each CKD stratum. The primary endpoint was the composite occurrence of all-cause death, stroke or myocardial infarction [major adverse cardiovascular and cerebrovascular events (MACCE)]. Event rates were estimated at 5 years using the Kaplan-Meier approach and hazard ratios (HRs) for CABG (vs. PCI) were generated using Cox regression. RESULTS: Patients with CKD (mean eGFR 47 mL/min/1.73m2) were older and more often female compared to those without renal impairment. Over a median follow-up of 3.8 years, the effect of CABG on MACCE was consistent among those with CKD (26.0% vs. 35.6%; HR [95% CI]: 0.73 [0.50-1.05]) and without CKD (16.2% vs. 23.6%; HR [95% CI)]: 0.76 [0.58-1.00]) with no evidence of interaction (pint = 0.83). Stroke rates were non-significantly higher with CABG whereas rates of MI and repeat revascularization were significantly reduced with CABG in both groups. CONCLUSIONS: Compared to PCI, the effects of CABG on long-term risks for MACCE observed in the FREEDOM trial are preserved among patients with mild to moderate CKD.