Real-World Evaluation of Dosing in Patients Converted From Insulin Glargine (Lantus) to Insulin Glargine (Basaglar).

Background: Basaglar, insulin glargine (BGlar; Eli Lilly, Indianapolis, IN), a follow-on biologic, was developed after the patent for Lantus, insulin glargine (LGlar; Sanofi-Aventis, Paris, France) expired. Objective: To compare the dosing and hemoglobin A1C (A1C)-lowering effects of BGlar compared with LGlar in a real-world setting. Methods: Adult patients, at 5 clinics, with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) who were converted from LGlar to BGlar were included in this retrospective observational study. The primary outcome compared mean basal insulin dose (U/d) from the date of conversion to 6 months. Basal insulin and total daily insulin doses were also compared from baseline to 3- and 12-months postconversion, as also change in A1C, body weight, and estimated monthly acquisition costs of basal insulin. Results: Of the 225 patients included, 56% were male, and 81% had T2DM. The mean conversion dose (U/d) of LGlar was 46.3 ± 32.7. There was no significant difference in the mean BGlar dose (U/d) at 6 months (45.9 ± 33.5; P = 0.52), nor was there a statistical difference at 3 or 12 months. There were no significant differences in change in A1C at any time point. The estimated monthly acquisition cost of BGlar was significantly less than that for LGlar at conversion ($286 vs $341, P < 0.001) and 6 months ($290 vs $351, P < 0.001) respectively. Conclusion/Relevance: The results of this retrospective study suggest that BGlar resulted in similar glycemic outcomes compared with LGlar in a real-world setting and may be a preferable option in a value-based health care environment.

Effect of a Rivaroxaban Patient Assistance Kit (R-PAK) for Patients Discharged With Rivaroxaban: A Randomized Controlled Trial.

Background: The combination of poor health literacy and a complex dosing regimen/transition for rivaroxaban in venous thromboembolism (VTE) treatment may increase the likelihood of negative clinical outcomes secondary to nonadherence. Objective: The aim was to determine if a Rivaroxaban Patient Assistance Kit (R-PAK) given at hospital discharge increases proper dose transition and overall patient adherence. Methods: This prospective, randomized, controlled trial was conducted at an 859-bed academic medical center. Patients were randomized into 2 groups. In the treatment group, patients received the R-PAK with counseling at discharge, whereas patients in the control group received discharge counseling alone. In addition, patients were contacted after 21 days of therapy to assess dose transition, adherence, satisfaction, and safety. The primary outcome was percentage of patients who properly transitioned to rivaroxaban once daily on day 22. Results: Twenty-five patients were enrolled; 12 received an R-PAK, whereas 13 comprised the control group. No difference in the baseline assessment of health literacy status was noted (P = 1.00). Proper transition to daily administration on day 22 was no different between the groups (P = .891). Adherence was reported in 99.8% of R-PAK patients and 97.65% of control patients (P = .074). Side effects were rarely reported. Conclusions: The use of an R-PAK for the treatment of VTE was not associated with an improvement in transition to daily administration; however, both groups had high rates of overall adherence. Pharmacist counseling/education was provided in both groups and is an important component to include in any patient discharge, especially for medications with dose transitions.

Conception of a Personalized Medication Adherence Discharge Kit for Rivaroxaban.

Purpose: Due to a lack of necessary monitoring with rivaroxaban, patients have fewer opportunities for education, adherence reinforcement, and follow-up. If rivaroxaban is taken incorrectly, patients are at increased risk for adverse events. The objective was to create personalized rivaroxaban patient adherence kits (R-PAKs) to enhance successful transition from 15 mg twice daily to 20 mg once daily on day 22 of venous thromboembolism (VTE) treatment. Summary: A review of rivaroxaban drug information and existing medication adherence tools was completed to increase understanding of ways to improve adherence. Clinical pharmacists identified several concerns the R-PAK should address, including patient understanding of correct dose, administration timing, serious adverse effects, and importance of compliance, along with loss to follow-up by a health care provider. In the pilot phase, 100 R-PAKs were created. Each kit includes an educational handout describing adverse effects, administration, and monitoring; a reminder card with dosing information, date to transition, and emergency contact information; and a personalized 28-day pill organizer containing customized dividers to correlate with the first 21 days of treatment. Color-coded stickers denote the first day of starting twice-daily therapy upon discharge and the day of transition to once-daily dosing. The items were distributed in tote bags at discharge along with pharmacist education. Conclusion: The R-PAKs are being used at a community teaching hospital for patients newly diagnosed with VTE who are discharged on rivaroxaban. The concept of a personalized medication box could be modified for any medication that requires high compliance or dose transitions.

Mirabegron: a Beta-3 agonist for overactive bladder.

OBJECTIVE: To review the literature regarding the efficacy and safety of mirabegron for the treatment of overactive bladder (OAB). DATA SOURCES: A literature search was performed using MEDLINE (PubMed) prior to December 31, 2013, using the terms "mirabegron" and "randomized-controlled trial." STUDY SELECTION/DATA EXTRACTION: All published, double-blind, randomized-controlled trials assessing mirabegron were included. Articles were reviewed and included if mirabegron was used as monotherapy and if the primary outcome analyzed drug efficacy. DATA SYNTHESIS: The efficacy of mirabegron for the treatment of OAB has been demonstrated in the selected five randomized, placebo-controlled trials. The majority of these trials lasted 12 weeks and compared various doses of mirabegron with placebo and/or tolterodine extended-release (ER). Primary efficacy outcomes for the trials included mean number of micturitions per 24 hours and mean number of incontinence episodes per 24 hours. Included trials showed statistically significant reductions in both efficacy outcomes for various doses of mirabegron when compared with placebo. CONCLUSION: Based on the trials reviewed, mirabegron has been efficacious in reducing mean number of micturitions and incontinence episodes per 24 hours, as well as in improving other secondary outcomes such as OAB symptoms and quality-of-life measures. Common adverse drug events seen with mirabegron include: hypertension, nasopharyngitis, urinary tract infections, headache, constipation, upper respiratory tract infection, arthralgia, diarrhea, tachycardia, abdominal pain, and fatigue. Given the efficacy and safety data currently available, mirabegron represents a reasonable alternative to antimuscarinics for patients with OAB. Future studies are needed to determine the utility of mirabegron for OAB in a variety of demographics.

Bevacizumab for the treatment of neovascular age-related macular degeneration.

OBJECTIVE: To review data regarding the efficacy and safety of bevacizumab for the treatment of neovascular age-related macular degeneration (nARMD). DATA SOURCES: Literature was searched using MEDLINE (1976-September 2011) and EMBASE (1973-September 2011). Search terms included bevacizumab, Avastin, neovascular macular degeneration, age-related macular degeneration, vascular endothelial growth factor, intravitreal, and safety. Reference citations were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All randomized clinical trials published in English with data assessing the safety and efficacy of bevacizumab for nARMD were evaluated. DATA SYNTHESIS: The only Food and Drug Administration-approved treatments for nARMD are photodynamic therapy (PDT) with verteporfin, intravitreal pegaptanib, and ranibizumab. However, bevacizumab has gained attention as a potential agent in treating nARMD and is now widely used in practice. PDT with verteporfin and pegaptanib has shown only stabilization of visual acuity (VA). When the efficacy of bevacizumab was compared to these therapies, bevacizumab clinically and statistically improved VA outcomes. When compared to ranibizumab, which has also been shown to improve VA, bevacizumab showed no significant difference in VA outcomes and was associated with a decrease in average annual cost of $22,805. CONCLUSIONS: Bevacizumab administered intravitreally is appropriate for prevention of vision loss and recovery of VA in patients with nARMD. Although further analysis of long-term effects of bevacizumab on VA and safety is needed, it is potentially a more cost-effective option than ranibizumab for the treatment of nARMD.

Anti-CD3 monoclonal antibodies for the prevention and treatment of type 1 diabetes: A literature review.

PURPOSE: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of beta cells, resulting in a loss of insulin production. Patients with T1D carry a substantial disease burden as well as substantial short-term and long-term risks associated with inadequate glycemic control. Currently, treatment mainly consists of insulin, which only treats the symptoms of T1D and not the root cause. Thus, disease-modifying agents such as anti-CD3 monoclonal antibodies (mAbs) that target the autoimmune destruction of beta cells in T1D would provide significant relief and health benefits for patients with T1D. This review summarizes the clinical evidence regarding the safety and efficacy of anti-CD3 mAbs in the prevention and treatment of T1D. SUMMARY: A total of 27 studies reporting or evaluating data from clinical trials involving otelixizumab and teplizumab were included in the review. Anti-CD3 mAbs have shown significant benefits in both patients at high risk for T1D and those with recent-onset T1D. In high-risk populations, anti-CD3 mAbs delayed time to diagnosis, preserved C-peptide levels, and improved metabolic parameters. In recent-onset T1D, anti-CD3 mAbs preserved C-peptide levels and reduced insulin needs for extended periods. Anti-CD3 mAb therapy appears to be safe, with primarily transient and self-limiting adverse effects and no negative long-term effects. CONCLUSION: Anti-CD3 mAbs are promising disease-modifying treatments for T1D. Their role in T1D may introduce short-term and long-term benefits with the potential to mitigate the significant disease burden; however, more evidence is required for an accurate assessment.

Insulin Dose Adjustment Following Bariatric Surgery, a Review of Available Literature.

Bariatric surgery is a known and effective treatment for type 2 diabetes mellitus. Patients with type 1 diabetes mellitus and exogenous insulin-requiring type 2 diabetes mellitus require adjusted insulin dosing after surgery to avoid hypoglycemia. This review describes insulin dose adjustments following a variety of bariatric procedures. After searching the available literature and assessing for eligibility, 8 articles were included. The Johns Hopkins Research Evidence Appraisal Tool for literature appraisal was used. The results of this review reveal insulin dose adjustment varies based upon surgical procedure type and time of follow-up from the procedure.

Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

OBJECTIVE: To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy. DATA SOURCE: PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All studies including humans that were published in English with data describing HPV vaccine administration in pregnancy were evaluated. DATA SYNTHESIS: Two combined analyses of 7 Phase 3 efficacy trials have retrospectively evaluated the safety of unintentional administration of either the bivalent (n = 1786) or quadrivalent (n = 2085) HPV vaccine during pregnancy. In addition, postmarketing pregnancy registry surveillance data (prospective, n = 787; retrospective, n = 76) for the quadrivalent HPV vaccine have been published. However, only 279 pregnancies from the studies and 90 pregnancies from the registry occurred within 30 days of receiving the vaccination. Overall, the vaccine does not appear to be associated with an increased risk of spontaneous abortion, fetal malformations, or adverse pregnancy outcomes beyond that found in the general population. Although the data are limited, neither HPV vaccine appears to be associated with an increased risk of adverse pregnancy outcomes. However, limitations of the data include small patient populations, minimal to no adjustments for factors known to influence pregnancy outcomes or malformations, and the majority of the available pregnancy data are from retrospective analysis of Phase 3 efficacy trials. CONCLUSIONS: Neither HPV vaccine should be routinely administered during pregnancy. If a pregnancy occurs midseries, the remaining vaccines should be given after pregnancy completion. Further studies are required to determine actual risk.

The prophylactic role for the human papillomavirus quadrivalent vaccine in males.

OBJECTIVE: To determine the role of human papillomavirus (HPV) quadrivalent vaccine in males. DATA SOURCE: PubMed (1966-March 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, quadrivalent, males, cancer, and genital warts. Reference citations were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing HPV quadrivalent vaccine administration in males were evaluated. DATA SYNTHESIS: The HPV quadrivalent vaccine is currently recommended in females, but its role in males is still being defined. Three clinical trials evaluated the immunogenicity and tolerability of the vaccine in more than 1100 males 9-26 years of age. Greater than 99.5% of males seroconverted for HPV 6, 11, 16, and 18 at 1 month post-completion and titers were found to be numerically higher than those in females 16-26 years old. One study found that immune response persisted in >92.5% of males at 1 year. The results show high efficacy against detection of new anogenital lesions in males 29 months after receiving the quadrivalent HPV vaccine. In addition, the quadrivalent HPV vaccine appears to be well tolerated, with the most common adverse effects being syncope, fever, local site reactions, dizziness, nausea, and headache. CONCLUSIONS: The HPV quadrivalent vaccine appears to be safe and induces an effective immune response in males. It may also decrease the incidence of anogenital and penile cancer, although current data are limited in number and duration of follow-up. Further analysis of the long-term immunogenicity and effects on HPV-associated complications is needed.

Nicotine replacement therapy effect on pregnancy outcomes.

OBJECTIVE: To review data assessing the effects of nicotine replacement therapy (NRT) during pregnancy on fetal, neonatal, and maternal outcomes. DATA SOURCES: A literature search of PubMed (1966-July 2010) was performed using the terms smoking, smoking cessation, pregnancy, and nicotine replacement therapy. Bibliographies and the Cochrane Database were reviewed to identify additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing NRT effects on pregnancy outcomes or malformations as a primary or secondary outcome were evaluated. DATA SYNTHESIS: Currently, behavior modification therapy is recommended for smoking cessation in pregnancy as first-line treatment, but NRT should be offered to patients who are not successful. NRT is currently a pregnancy category D medication. Pregnancy outcomes and malformation rates for NRT in pregnancy were evaluated as either primary or secondary outcomes in several trials. Four studies examined pregnancy outcomes after a full course of nicotine gum or patch therapy. NRT use significantly decreased the risk of preterm delivery and low birth weight compared to that of smokers. Only 1 study evaluated the risk of malformations after exposure to the NRT patch during the first trimester. In a retrospective analysis, NRT users had an increased risk for any fetal malformation but not for major or musculoskeletal ones. However, no adjustments were made for many known factors associated with malformations. CONCLUSIONS: Behavior modification therapy should always be the first method tried for smoking cessation in the pregnant population. If behavior modification therapy is attempted without success, NRT should be offered because of decreased risk for low birth weight and preterm delivery compared to continued smoking. Additionally, NRT does not appear to increase the risk for malformations.

Thrombolytic Therapy in Wake-Up Stroke Patients.

OBJECTIVE: The aim of the study is to review existing and ongoing trial data on wake-up stroke (WUS) patients for thrombolytic therapy. METHODS: A literature search was conducted in PubMed (conception-October 2016) using the terms wake-up stroke, acute ischemic stroke, wake-up thrombolysis, computed tomography imaging in wake-up stroke, and magnetic resonance imaging in wake-up stroke. Ongoing trials were found using the ClinicalTrials.gov website. RESULTS: The search yielded 61 articles in PubMed and 7 ongoing trials. After removing duplicate/irrelevant articles, 33 articles and relevant references were reviewed; of these, 6 articles and 3 ongoing trials were included. Two retrospective studies evaluating the characteristics between WUS and known-onset stroke were identified; the only significant difference between groups was the ability to receive treatment with tissue plasminogen activator (tPA). One study suggested that perfusion brain imaging may be useful to identify patients that may benefit from tPA. In addition, 3 studies have evaluated WUS treatment; all used different methods to identify potential patients. Two of 3 studies showed that treatment with tPA is associated with better outcomes when controlling for baseline National Institutes of Health Stroke Scale. No difference in safety outcomes was seen between groups for all 3 studies. CONCLUSIONS: Available data suggest promising strategies to identify WUS patients who may benefit from thrombolysis. Once on-going trials are complete, there may be sufficient information to redefine tPA eligibility for previously excluded patients.