The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

Marco D DiBonaventura,1 William Wong,2 Bijal Shah-Manek,3,4 Mathias Schulz2 1Ipsos Healthcare, Global Evidence, Value & Access, New York, NY, 2Genentech, US Medical Affairs, San Francisco, CA, 3Ipsos Healthcare, Global Evidence, Value & Access, San Francisco, CA, 4College of Pharmacy, Touro University California, CA, USA Background: Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods: Participating oncologists (N=95) in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor), collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results: A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male). The patients in our sample were older (median age of 60 vs 53 years), were more likely to be current smokers (12% vs 1%), had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0), and were less likely to have an adenocarcinoma histology (83% vs 96%) relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively) as was the disease control rate (89.9% vs 78.8%, respectively), though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0%) and dose reductions (3.4%) due to adverse events were uncommon in alectinib.Conclusion: Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically diverse than patients in published trials. Real-world response rates were high and similar to those reported in clinical studies, though there is some variation by patient characteristics. Alectinib was well tolerated in clinical practice as reflected by the rates of discontinuation, dose reductions, and dose interruptions. Keywords: alectinib, anaplastic lymphoma kinase, non-small-cell lung cancer, treatment patterns, outcomes, ALK inhibitor, ALK+&nbsp

Medication Regimen Complexity and A1C Goal Attainment in Underserved Adults with Type 2 Diabetes: A Cross-Sectional Study

Background: From 2009 to 2012, 51.8% of American adults with diabetes had a hemoglobin A1C (A1C) &gt;7.0%. The complexity of antidiabetic medication regimens may have an impact on glycemic control. Objective: The primary objective was to test the hypothesis that higher diabetes-specific medication regimen complexity index (MRCI) was associated with lower attainment of A1C goal &lt;7.0% in an underserved, predominantly Hispanic population of adults with type 2 diabetes. Secondary analyses included less stringent A1C goals of &lt;8.0% and &lt;9.0% and overall patient-level MRCI. Methods: This study was a retrospective, observational, cross-sectional study of individuals with type 2 diabetes from January 2011 to January 2016. Data was obtained from the electronic medical record and MRCI was calculated using the 65-item validated Microsoft Access Version 1.0 medication regimen complexity electronic data capture tool. Logistic regression was used to compute unadjusted and adjusted odds ratios. Results: A total of 368 patients were included in the analysis. High diabetes-specific MRCI was associated with lower attainment of A1C goal &lt;7.0% (adjusted OR = 0.09; 95% CI = 0.04-0.18) controlling for age, gender, ethnicity, insurance, body mass index, smoking status, hypertension, and hyperlipidemia. Similar results were obtained for the less stringent A1C goals. However, results for overall patient-level MRCI were mixed. Conclusions: Higher diabetes-specific medication regimen complexity was associated with poorer glycemic control. Simplifying antidiabetic medication regimens, especially where the treatment guidelines give no preference, could be a step toward achieving treatment goals. </jats:p

Adherence to recommended clinical guidelines in extensive disease small-cell lung cancer across the US, Europe, and Japan

Marco D DiBonaventura,1 Bijal Shah-Manek,2 Karen Higginbottom,1 John R Penrod,3 Yong Yuan3 1Global Evidence Value and Access (GEVA), Ipsos Healthcare, Mahwah, NJ, USA; 2Global Evidence Value and Access (GEVA), Ipsos Healthcare, San Francisco, CA, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA Purpose: This study compared real-world treatment patterns of patients with extensive disease small-cell lung cancer (ED-SCLC) across regions and by platinum resistance/platinum sensitivity (PR/PS) and established if these patterns were in line with published guidelines. Patients and methods: The data source was the Oncology Monitor, a global database using retrospective medical chart reviews of oncology patients treated with anticancer drugs. All patients diagnosed with ED-SCLC from January 2014 through December 2016 in the US, and in France, Germany, Italy, Spain, and the UK (European Union; EU5), and Japan were included. Results: Of 5,849 treated patients, 73.4%, 19.8% and 6.8% received first, second, or third/later lines (1L, 2L, 3L) of therapy, respectively. The most frequent 1L treatment, platinum + etoposide, was significantly more common in the US (87.0%) than in the EU5 (82.1%) or Japan (73.3%) (P&lt;0.05). Platinum + irinotecan was a common 1L treatment in Japan (22.7%) but not in the US (2.0%) or EU5 (0.5%, P&lt;0.0001). Topotecan was the most common 2L treatment in the US and EU5, but amrubicin was the most common in Japan. Among PR patients, 27.3%, 10.8%, and 36.4% received a platinum-based 2L therapy in the US, EU5, and Japan, respectively. Among PS patients, approximately half were not re-challenged with a 2L platinum-based therapy across all regions. Conclusion: In contrast to treatment guidelines, a significant proportion of real-world PR patients were re-challenged with a 2L platinum-based therapy, while conversely, many PS patients did not receive platinum-based therapies in 2L. This study highlights a lack of a consistent paradigm for 2L ED-SCLC treatment, limited therapeutic options, and an unmet need among SCLC patients. Keywords: small-cell lung cancer, real-world treatment patterns, clinical guideline

Characteristics and Treatment Patterns of Patients with Diabetic Macular Edema Non-Responsive to Anti-Vascular Endothelial Growth Factor Treatment in Ontario, Canada

Sohel Somani,1 Keyvan Koushan,2 Bijal Shah-Manek,3 Daniel Mercer,4 Thula Kanagenthiran,5 Changgeng Zhao,5 Ali Alobaidi5 1Department of Ophthalmology and Vision Sciences, University of Toronto and Uptown Eye Specialists, Brampton, Canada; 2Toronto Retina Institute, Toronto, Canada; 3Health Economics and Outcomes Research, Noesis Healthcare Technologies, Inc., Redwood City, CA, USA; 4Genesis Research, Hoboken, NJ, USA; 5Allergan, an AbbVie Company, Irvine, CA, USACorrespondence: Sohel Somani, Email [email protected]: To understand the demographics, clinical characteristics, treatment patterns, visual and anatomic responses of patients with diabetic macular edema (DME) initially treated with anti-vascular endothelial growth factor (anti-VEGF) agents in the real-world clinical setting.Patients and Methods: This retrospective cohort study used electronic health records to identify consecutively presenting patients with DME who received their first documented anti-VEGF injection (index injection) on or after 1 October 2015 and before 30 September 2016 (index period) at 4 clinical sites in Ontario, Canada. Patients receiving anti-VEGF injections in the study eye were followed for ≥ 18 months. After the first 3 monthly injections, patients were classified as “responder” (≥ 20% reduction in central retinal thickness [CRT] from index date) or “nonresponder” (< 20% reduction in CRT) to anti-VEGF treatment.Results: At 12 months, change from baseline (CFB) in best visual acuity (BVA) of responders (n = 30) was mean (SD) 12.8 (13.00) letters; CFB in nonresponders (n = 56) was 3.2 (16.3) letters. Sensitivity analyses stratified by initial BVA were supportive. Mean (SD) change in CRT (μm) was − 160.4 (111.4) in responders and − 62.2 (98.6) in nonresponders. While changes in anti-VEGF therapy were lower in responders versus nonresponders (10.0% vs 23.2%), mean number of injections was similar (8.3 in each cohort).Conclusion: Despite receiving a substantial number of injections and requiring changes in therapy more frequently, nonresponders showed a lack of clinically meaningful change in BVA and CRT. Nonresponders could be identified after 3 anti-VEGF injections. There remains an unmet need for treatment options in patients with DME who show a nonresponse after 3 months of anti-VEGF treatment.Keywords: real-world evidence, diabetic macular edema, drug therapy, anti-vascular endothelial growth factor, visual acuit