Research Spotlight

Wu, J. J., J. F. Merola, S. R. Feldman, A. Menter and M. Lebwohl (2020). “Treatment of Psoriasis with Secukinumab in Challenging Patient Scenarios: A Review of the Available Evidence.” Dermatol Ther (Heidelb) Apr 2. [Epub ahead of print].

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Psoriasis (PsO) is a common, systemic, chronic, inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling. PsO is associated with a high prevalence of comorbidities, including other autoimmune diseases and malignancies. Furthermore, special populations, such as pregnant, pediatric, and elderly patients, and those with erythrodermic PsO, are challenging to treat and require tightly monitored disease and treatment management. Because certain populations have demographic or clinical characteristics that can affect the presentation of PsO and complicate treatment responses, these patient populations are largely excluded from clinical trials; therefore, most clinical evidence for the treatment of these patients is derived from case reports and series. Secukinumab, a fully human monoclonal interleukin-17A antibody, has been shown in several clinical trials to be effective and safe for the treatment of PsO; however, these studies offer only limited data on the use of secukinumab in patients with chronic illnesses or in special populations. This review explores the use of secukinumab for PsO in special populations, including pregnant women, children, elderly people, patients with erythrodermic PsO, and those with chronic illnesses, including latent tuberculosis, hepatitis B and C, HIV, multiple sclerosis, and malignancies.

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The authors would like to correct the error in Table 1.

Witting, M. D., K. M. Hu, A. A. Westreich, S. Tewelde, A. Farzad and A. Mattu (2020). “Evaluation of Spodick’s Sign and Other Electrocardiographic Findings as Indicators of STEMI and Pericarditis.” J Emerg Med Mar 25. pii: S0736-4679(20)30020-2. [Epub ahead of print].

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BACKGROUND: Patients with ST elevation on electrocardiogram (ECG) could have ST elevation myocardial infarction (STEMI) or pericarditis. Spodick’s sign, a downsloping of the ECG baseline (the T-P segment), has been described, but not validated, as a sign of pericarditis. OBJECTIVE: This study estimates the frequency of Spodick’s sign and other findings in patients diagnosed with STEMI and those with pericarditis. METHODS: In this retrospective review, we selected charts that met prospective definitions of STEMI (cases) and pericarditis (controls). We excluded patients whose ECGs lacked ST elevation. An authority on electrocardiography reviewed all ECGs, noting the presence or absence of Spodick’s sign, ST depression (in leads besides V1 and aVR), PR depression, greater ST elevation in lead III than in lead II (III > II), abrupt take-off of ST segment (the RT checkmark sign), and upward or horizontal ST convexity. We quantified strength of association using odds ratio (OR) with 95% confidence interval (CI). RESULTS: One hundred and sixty-five patients met criteria for STEMI and 42 met those for pericarditis. Spodick’s sign occurred in 5% of patients with STEMI (95% CI 3-10%) and 29% of patients with pericarditis (95% CI 16-45%). All other findings statistically distinguished STEMI from pericarditis, but ST depression (OR 31), III > II (OR 21), and absence of PR depression (OR 12) had the greatest OR values. CONCLUSIONS: Spodick’s sign is statistically associated with pericarditis, but it is seen in 5% of patients with STEMI. Among other findings, ST depression, III > II, and absence of PR depression were the most discriminating.

Winder, G. S. and S. K. Asrani (2020). “Payer coverage and liver transplantation for alcohol associated hepatitis.” Liver Transpl Mar 21. [Epub ahead of print].

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We duly note the insurance challenges discussed by Eswaran and Chan. Many insurance payers continue to require fixed pre-transplant sobriety periods (i.e. “6-month rules”) despite the lack of evidence to support them(1-3). While payers reserve the right to skepticism about any center’s evolving policies regarding liver transplantation (LT) for alcohol-associated hepatitis (AH), we anticipate that payers’ approach to these patients will progress. As 1) transplant centers update their institutional criteria regarding LT/AH, 2) acceptable outcomes are demonstrated in a transparent manner and 3) professional societies offer guidance, we anticipate that insurance payers’ policies will follow suit.

Weir, M. R., P. A. McCullough, J. B. Buse and J. Anderson (2020). “Renal and Cardiovascular Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease: Perspectives on the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial Results.” Am J Nephrol Mar 13:1-13. [Epub ahead of print].

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BACKGROUND: Chronic kidney disease (CKD) risk is elevated in patients with type 2 diabetes mellitus (T2DM). Disease management in these patients has been generally focused on glycemic control and controlling other renal and cardiac risk factors as, historically, few protective therapies have been available. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation -(CREDENCE) trial of canagliflozin was the first study to demonstrate renal protection with a sodium glucose co-transporter 2 inhibitor in patients with T2DM and CKD, and these results could have important implications for clinical practice. SUMMARY: In CREDENCE, participants with T2DM and estimated glomerular filtration rate 30-<90 mL/min/1.73 m2 and urinary albumin-creatinine ratio >300-5,000 mg/g who were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for >/=4 weeks prior to randomization at either the maximum labeled or tolerated dose were randomized to receive either canagliflozin 100 mg or placebo. Canagliflozin significantly reduced the risk of the primary composite outcome of doubling of serum creatinine, end-stage kidney disease, or renal or cardiovascular (CV) death compared with placebo (hazard ratio 0.70, 95% CI 0.59-0.82; p = 0.00001). Canagliflozin also reduced the risk of secondary renal and CV outcomes. The safety profile of canagliflozin in CREDENCE was generally similar to previous studies of canagliflozin. No imbalances were observed between canagliflozin and placebo in the risk of amputation or fracture in the CREDENCE population. Key Messages: The positive renal and CV effects of canagliflozin observed in the -CREDENCE trial could have a substantial impact on improving outcomes for patients with T2DM and CKD.

Wang, M., J. Munoz, A. Goy, F. L. Locke, C. A. Jacobson, B. T. Hill, J. M. Timmerman, H. Holmes, S. Jaglowski, I. W. Flinn, P. A. McSweeney, D. B. Miklos, J. M. Pagel, M. J. Kersten, N. Milpied, H. Fung, M. S. Topp, R. Houot, A. Beitinjaneh, W. Peng, L. Zheng, J. M. Rossi, R. K. Jain, A. V. Rao and P. M. Reagan (2020). “KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma.” N Engl J Med 382(14): 1331-1342.

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BACKGROUND: Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton’s tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma. METHODS: In a multicenter, phase 2 trial, we evaluated KTE-X19 in patients with relapsed or refractory mantle-cell lymphoma. Patients had disease that had relapsed or was refractory after the receipt of up to five previous therapies; all patients had to have received BTK inhibitor therapy previously. Patients underwent leukapheresis and optional bridging therapy, followed by conditioning chemotherapy and a single infusion of KTE-X19 at a dose of 2×10(6) CAR T cells per kilogram of body weight. The primary end point was the percentage of patients with an objective response (complete or partial response) as assessed by an independent radiologic review committee according to the Lugano classification. Per the protocol, the primary efficacy analysis was to be conducted after 60 patients had been treated and followed for 7 months. RESULTS: A total of 74 patients were enrolled. KTE-X19 was manufactured for 71 patients and administered to 68. The primary efficacy analysis showed that 93% (95% confidence interval [CI], 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred. CONCLUSIONS: KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma. The therapy led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies. (Funded by Kite, a Gilead company; ZUMA-2 ClinicalTrials.gov number, NCT02601313.).