Research Spotlight

Menter, A., A. Armstrong, A. Van Voorhees, C. Liu and A. Jacobson (2020). “Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics.” Dermatol Ther (Heidelb) Jun 12. [Epub ahead of print.].

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While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy.

Bailey, K. L., H. Smith, S. K. Mathai, J. Huber, M. Yacoub, I. V. Yang, T. A. Wyatt, K. Kechris and E. L. Burnham (2020). “Alcohol Use Disorders Are Associated With a Unique Impact on Airway Epithelial Cell Gene Expression.” Alcohol Clin Exp Res Jun 11. [Epub ahead of print.].

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BACKGROUND: Alcohol use disorders (AUDs) and cigarette smoking both increase risk for the development of community-acquired pneumonia (CAP), likely through adverse effects on proximal airway mucociliary clearance and pathogen recognition. Smoking-related alterations on airway gene expression are well described, but little is known about the impact of AUDs. We measured gene expression in human airway epithelial cells (AECs), hypothesizing that AUDs would be associated with novel differences in gene expression that could alter risk for CAP. METHODS: Bronchoscopy with airway brushings was performed in participants with AUDs and controls to obtain AECs. An AUD Identification Test was used to define AUD. RNA was extracted from AECs, and mRNA expression data were collected on an Agilent micro-array. Differential expression analyses were performed on the filtered and normalized data with correction for multiple testing. Enrichment analyses were performed using clusterProfiler. RESULTS: Expression data from 19 control and 18 AUD participants were evaluated. After adjustment for smoking, AUDs were associated with significant differential expression of 520 AEC genes, including genes for ribosomal proteins and genes involved in protein folding. Enrichment analyses indicated significant differential expression of 24 pathways in AUDs, including those implicated in protein targeting to membrane and viral gene expression. Smoking-associated AEC gene expression differences mirrored previous reports, but differed from those associated with AUDs. CONCLUSIONS: AUDs have a distinct impact on AEC gene expression that may influence proximal airway function independent of smoking. Alcohol-associated alterations may influence risk for CAP through modifying key mechanisms important in protecting proximal airway integrity.

Mamun, A., H. Kitzman and L. Dodgen (2020). “Reducing metabolic syndrome through a community-based lifestyle intervention in African American women.” Nutr Metab Cardiovasc Dis Jun 12;S0939-4753(20)30232-5. [Epub ahead of print.].

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BACKGROUND AND AIMS: Metabolic syndrome (MetS) increases the risk of cardiovascular disease and type 2 diabetes. Despite a higher prevalence of MetS in African American (AA) women, little is known about the effectiveness of lifestyle interventions in improving metabolic markers in this high-risk group. This study investigated the effectiveness of a community-based lifestyle intervention delivered by lay health coaches in reducing MetS among AA women. METHODS AND RESULTS: A cluster-randomized diabetes prevention program (DPP) was implemented in 11 churches utilizing a community-based participatory research (CBPR) approach to develop and deliver the interventions. A total of 221 adults, AA women who were overweight or obese, and did not have diabetes were included in this study. The prevalence of MetS was 42.08% before receiving the DPP intervention and 31.22% after the intervention that represented a 10.86% absolute reduction and a 25.81% relative reduction from baseline. The adjusted odds ratio (OR) of being free from MetS at post-intervention in contrast to baseline was 2.14 (p = 0.02). Factors that increased the odds of being free from MetS were younger age, reduction in intake of total calories, total fat, saturated and trans-fat, and dietary sodium. CONCLUSION: A faith adapted lifestyle intervention held in church settings and delivered by minimally trained lay health coaches reduced the prevalence of MetS in AA women who were overweight or obese. Findings from this study can be used to translate evidence into public health programs at the community level for the prevention of type 2 diabetes and cardiovascular disease.

Marquis-Gravel, G., A. Stebbins, A. S. Kosinski, M. L. Cox, J. K. Harrison, G. C. Hughes, V. H. Thourani, T. G. Gleason, A. J. Kirtane, J. D. Carroll, M. J. Mack and S. Vemulapalli (2020). “Geographic Access to Transcatheter Aortic Valve Replacement Centers in the United States: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.” JAMA Cardiol Jun 10;e201725. [Epub ahead of print.].

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IMPORTANCE: Geographic access to transcatheter aortic replacement (TAVR) centers varies in the United States as a result of controlled expansion through minimum volume requirements. OBJECTIVE: To describe the current geographic access to TAVR centers in the United States. DESIGN, SETTING, AND PARTICIPANTS: Observational study from June 1, 2015, to June 30, 2017. United States census data were used to describe access to TAVR center. Google Maps and the Society of Thoracic Surgeons American College of Cardiology Transcatheter Valve Therapy Registry were used to describe characteristics of patients undergoing successful TAVR according to proximity to implanting center. The study analyzed 47 527 537 individuals 65 years and older in the United States and 31 098 patients who underwent successful transfemoral TAVR, were linked to fee-for-service Medicare, and had a measurable driving time. MAIN OUTCOMES AND MEASURES: Median driving distance to a TAVR center. RESULTS: Among 40 537 zip codes in the United States, 490 (1.2%) contained a TAVR center, and among 305 hospital referral regions (HRR), 234 (76.7%) contained a TAVR center. Of the 31 749 patients who underwent successful transfemoral TAVR and were linked to fee-for-service Medicare, 31 098 had a measurable driving time. Mean (SD) age was 82.4 (6.9) years, 14 697 patients (47.3%) were women, and 7422 (23.87%) lived in a rural area. This translated to 1 232 568 of 47 527 537 individuals (2.6%) 65 years and older living in a zip code with a TAVR center and 43 789 169 (92.1%) living in an HRR with a TAVR center. Among 31 749 patients who underwent successful transfemoral TAVR and were linked to fee-for-service Medicare, 31 098 had a measurable driving time. All of these patients (100.0%) underwent their procedure in a TAVR center within their HRR, with 1350 (4.3%) undergoing TAVR in a center within their home zip code. Median driving time to implanting TAVR center was 35.0 minutes (IQR, 20.0-70.0 minutes), ranging from 2.0 minutes to 18 hours and 48 minutes. CONCLUSIONS AND RELEVANCE: Most US individuals 65 years and older live in an HRR with a TAVR center. Among patients undergoing successful transfemoral TAVR, median driving time to implanting center was 35.0 minutes. Within the context of the US health care system, where certain advanced procedures and specialized care are centralized, TAVR services have significant penetration. More studies are required to evaluate the effect of geographic location of TAVR sites on access to TAVR procedures among individuals with an indication for a TAVR within the US population.

Sathananthan, J., P. Green, M. Finn, D. A. Wood, S. Lauck, A. Crowley, M. Alu, S. V. Arnold, D. Cohen, S. Kapadia, M. Mack, V. H. Thourani, S. Kodali, M. Leon and J. G. Webb (2020). “Prognostic implications of baseline 6-min walk test performance in intermediate risk patients undergoing transcatheter aortic valve replacement.” Catheter Cardiovasc Interv Jun 10. [Epub ahead of print.].

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BACKGROUND: While slow gait speed is known to be associated with poor outcomes in patients at high surgical risk who undergo transcatheter aortic valve replacement (TAVR), the prognostic significance of slow gait speed in intermediate risk TAVR patients is poorly understood. OBJECTIVES: We assessed the association between baseline 6-min walk test (6MWT) performance and both 2-year mortality and health status in intermediate risk patients undergoing TAVR as a part of the PARTNER II/S3i studies. METHODS: The association of baseline 6MWT with mortality over 2-years after TAVR was examined using Cox regression; both unadjusted and adjusted for age, left ventricular ejection fraction, coronary artery disease, pulmonary disease, renal insufficiency, and STS score. Patients were divided into four groups according to baseline 6MWT: unable to walk and in three equal tertiles of slow, medium, and fast walkers. Among surviving patients, improvement in 6MWT and quality of life were compared. RESULTS: Among 2,037 intermediate risk TAVR patients (mean age 81.7 years, STS score 5.6%), 8.2% were unable to walk. Baseline 6MWT was associated with all-cause mortality over 2 years (Hazard ratio (HR) 0.87 per 50 m, 95% confidence interval [CI] 0.83 to 0.92, p < .0001). Among surviving patients, the adjusted absolute change in 6MWT at 2 years improved for patients unable to walk (+134.1 m, 95% CI 102.1 to 166 m, p < .0001) and slow walkers (+60.5 m, 95% CI 42.8 to 78.2 m, p < .0001), but was unchanged for medium walkers (-7.3 m, 95% CI -24.3 to 9.6 m, p = .4), and declined for fast walkers (-41.3 m, 95% CI -58.7 to -23.9 m, p < .0001). CONCLUSION: Poor functional capacity is predictive of 2-year mortality in elderly intermediate risk patients undergoing TAVR. However, surviving patients with poor baseline functional capacity had significant improvement in 6MWT performance and quality of life at 2-years following TAVR.