A practical guide to selecting and using new ulcerative colitis therapies.

PURPOSE OF REVIEW: Several new biologics (mirizikizumab) and small molecules (upadacitinib, ozanimod, etrasimod) are approved for the treatment of moderate-to-severe ulcerative colitis. To date, there are no head-to-head trials to guide positioning and use of these newer agents. RECENT FINDINGS: From phase III clinical trials, in the biologic experienced patient, induction with ozanimod, etrasimod, and mirizikizumab had lower clinical remission rates, whereas upadacitinib's clinical remission rates remained similar. Indirect evidence using network meta-analysis suggests upadacitinib may be more efficacious than other advanced therapies for the treatment of ulcerative colitis in both the bio-naive and experienced patient. Upadacitinib was found to have the highest risk for adverse events. SUMMARY: These newer agents add novel mechanisms of action to the expanding therapeutic armamentarium of advanced therapies to treat ulcerative colitis. Based on expert opinion and available data to date, we propose a practical guide on positioning of these new agents for the treatment of ulcerative colitis. In mild-to-moderate disease, one should consider using ozanimod or etrasimod as first-line agents. In moderate-to-severe disease, we favor using mirizikizumab as first-line agent. In patients who have failed an anti-tumor necrosis factor agent, upadacitinib or mirizikizumab should be considered using patient factors and safety to guide one's decision between these two agents.

Primary care diabetes assessment when HbA1c and other measures of glycemia disagree.

AIMS: Although diabetes management decisions in primary care are typically based largely on HbA1c, mismatches between HbA1c and other measures of glycemia that are increasingly more available present challenges to optimal management. This study aimed to assess a systematic approach to identify the frequency of mismatches of potential clinical significance amongst various measures of glycemia in a primary care setting. METHODS: Following screening to exclude conditions known to affect HbA1c interpretation, HbA1c, and fructosamine were obtained and repeated after ∼90 days on 53 adults with prediabetes or type 2 diabetes. A subset of 13 participants with repeat labs wore continuous glucose monitoring (CGM) for 10 days. RESULTS: As expected, HbA1c and fructosamine only modestly correlated (initial R2 = 0.768/repeat R2 = 0.655). The HbA1c/fructosamine mismatch frequency of ± 0.5% (using the following regression HbA1c = 0.015 *fructosamine + 2.994 calculated from the initial sample) was 27.0%. Of the 13 participants with CGM data, HbA1c and CGM-based Glucose Management Indicator correlated at R2 = 0.786 with a mismatch frequency of ± 0.5% at 46.2% compared to a HbA1c/fructosamine mismatch frequency of ± 0.5% at 30.8%. CONCLUSIONS: HbA1c is frequently mismatched with fructosamine and CGM data. As each of the measures has strengths and weaknesses, the utilization of multiple different measures of glycemia may be informative for diabetes assessment in the clinical setting.

Risk Versus Benefit of Combined Aspirin and Warfarin Therapy in Patients With Atrial Fibrillation.

PURPOSE: Guidelines have differing recommendations for aspirin use in patients with an indication for anticoagulation. The purpose of this study was to evaluate the incidence of major bleeding and thromboembolic events (TEs) in patients with atrial fibrillation (AF) receiving warfarin alone (monotherapy group) versus warfarin plus aspirin (combination therapy group). METHODS: This was a retrospective, cohort study including patients from a pharmacist-run anticoagulation clinic. Inclusion criteria were patients with AF receiving anticoagulation between January 2013 and January 2014 observed over 5 years. RESULTS: One hundred forty-two patients were included in the combination group versus 89 in monotherapy group. In the combination group, 60 (42.3%) patients were on aspirin for no apparent indication, 19 (13.4%) had stable coronary artery disease and diabetes, and 26 (18.3%) had diabetes alone. Major bleeding occurred in 21 (14.9%) patients in the combination group versus 7 (7.9%) patients in the monotherapy group (odds ratio [OR] = 2.02, 95% confidence interval [CI]: 0.78-5.91; P = .17). TE occurred in 10 (7%) patients in the combination group versus 4 (4.5%) in the monotherapy group (OR = 1.61, 95% CI: 0.44-7.24; P = .57). There was no significant difference in bleeding (P = .85) or TE (P = .37) rates between aspirin indications in the combination group. CONCLUSION: Combination therapy versus monotherapy may increase bleeding risk with little benefit in decreasing AF-related stroke or cardiovascular events.

New Oral Anticoagulants: Clinical Parameters and Uses in Practice.

OBJECTIVE: This article serves as a resource for health care professionals by providing a summary of primary literature and guidelines for use of the available oral anticoagulant agents. The cost vs. efficacy aspects and reversibility of these medications are also addressed. DATA SOURCES, STUDY SELECTION, AND DATA SYNTHESIS: A PubMed search and Cochrane database review were conducted between June 15 and June 30, 2014, to find appropriate primary literature on each of the new oral anticoagulants. All phase 3 trials for apixaban, rivaroxaban, dabigatran, and edoxaban for the treatment of stroke prevention in atrial fibrillation (AF) and venous thromboembolism (VTE) were included. The American College of Chest Physicians guideline recommendations for stroke prevention in AF and VTE treatment, and the American Heart Association/American College of Cardiology guidelines for AF were reviewed, and pertinent information regarding the new anticoagulants from these guidelines is included in this review. A PubMed search was also used to identify cost-efficacy references and articles on reversibility of bleeding discussed in this paper. For all these articles, no further data analysis was performed; rather summaries and discussions of all of the articles included are provided in this review. CONCLUSION: The new oral anticoagulant agents have great potential in becoming standard therapy in both VTE and stroke prevention with AF. Initial clinical evidence proves they are clinically effective and potentially cost-effective for patients searching for an alternative for warfarin. Once reversal agents are developed and long-term use data become available, these agents will likely become common in many clinical practices.