Real-world ibrutinib dose reductions, holds and discontinuations in chronic lymphocytic leukemia.

Aim: A retrospective chart review of ibrutinib-treated patients with chronic lymphocytic leukemia (CLL) was conducted. Patients & methods: Adults with CLL who initiated ibrutinib were followed for ≥6 months (n = 180). Results: Twenty-five percent of first-line ibrutinib patients experienced ≥1 dose reduction, mainly due to adverse events (AEs; 79%). Treatment discontinuations and dose holds occurred in 20 and 34% of patients, respectively, most commonly due to AEs (73 and 74%). Approximately one-quarter of relapsed/refractory ibrutinib patients experienced ≥1 dose reduction, mainly due to AEs (88%). Treatment discontinuation and dose holds occurred in 40% of patients (58 and 76% due to AEs, respectively). Conclusion: Dose reductions, holds and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice.

Lay abstract Chronic lymphocytic leukemia (CLL) is a cancer that develops from a type of white blood cells called 'B cells.' Ibrutinib is a targeted therapy that inhibits the activity of a protein called Bruton's tyrosine kinase, which plays a key role in CLL. Patients receiving ibrutinib treatment can experience side effects ('adverse events'). In addition, patients may need to reduce their drug dose ('dose reductions') or stop treatment ('discontinuations') for a variety of reasons. We reviewed patients' charts to describe dose reductions and discontinuations in ibrutinib-treated patients with CLL. Our results indicate that dose reductions and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice, and that the most common reason was adverse events.

User testing and performance evaluation of the Electronic Quality Improvement Platform for Plans and Pharmacies.

OBJECTIVE: To user-test and evaluate a performance information management platform that makes standardized, benchmarked medication use quality data available to both health plans and community pharmacy organizations. SETTING: Multiple health/drug plans and multiple chain and independent pharmacies across the United States. EVALUATION: During the first phase of the study, user experience was measured via user satisfaction surveys and interviews with key personnel (pharmacists, pharmacy leaders, and health plan leadership). Improvements were subsequently made to the platform based on these findings. During the second phase of the study, the platform was implemented in a greater number of pharmacies and by a greater number of payers. User experience was then reevaluated to gather information for further improvements. RESULTS: The surveys and interviews revealed that users found the Web-based platform easy to use and beneficial in terms of understanding and comparing performance metrics. Primary concerns included lack of access to real-time data and patient-specific data. Many users also expressed uncertainty as to how they could use the information and data provided by the platform. CONCLUSION: The study findings indicate that while information management platforms can be used effectively in both pharmacy and health plan settings, future development is needed to ensure that the provided data can be transferred to pharmacy best practices and improved quality care.

Demographic differences in the treatment and control of glucose in type 2 diabetic patients: implications for health care practice.

OBJECTIVE: Identifying modifiable covariables that reduce demographic disparities in controlling type 2 diabetes could inform efforts to improve health equity. RESEARCH DESIGN AND METHODS: This retrospective study utilized electronic health record data on 22,285 adults with type 2 diabetes seen at 110 outpatient clinics in the Southeast U.S. from 2004-2008. Demographic differences in diabetes control and modifiable covariables which reduce those disparities were quantified using descriptive and logistic regression analysis. RESULTS: Patients were 55.8 +/- 14.6 (SD) years old, 57.5% women, 61.0% white: 39.0% black and had baseline body mass index 34. +/- .3 kg/ m2 and HbA1c 7.61 +/- 1.9%. The percentage with HbAlc <7% was higher in Whites than blacks (55.6% vs. 44.7%, P < .0001) and rose with age in all patients from 45.3% at <50, to 50.0% at 50-64, and 59.6% at > or =65 years, P < .001. white vs. black race (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.51-1.68) and age/ 10 years (OR 1.20/10 years, 95% CI 1.17-1.22) were predictors of HbAlc <7% in univariable logistic regression. In multivariable analysis, three modifiable covariables (initial HbAlc, therapeutic inertia, visit frequency) accounted for 47.9% of variance in diabetes control. When accounting for these modifiable covariables, the independent impact of race/ethnicity (OR 1.21, 95% CI 1.13-1.30) and age (OR 1.13, 95% Cl 1.11-1.16) on HbA1c control declined. CONCLUSIONS: Race and age-related difference in diabetes control declined significantly when modifiable covariates were considered. Greater attention to early diagnosis and treatment, ensuring regular healthcare visits and overcoming therapeutic inertia could improve diabetes control and health equity.

Budget impact of adding lesinurad for second-line treatment of gout: a US health plan perspective.

Aim: To estimate budget impact of adopting lesinurad as add-on to allopurinol for urate-lowering therapy in gout. Methods: A budget impact model was developed for a US payer perspective, using a Markov model to estimate costs, survival and discontinuation in a one-million-member health plan. The population included patients failing first-line gout therapy, followed for 5 years. Results: Incremental costs of adding lesinurad versus no lesinurad were US$241,907 and US$1,098,220 in first and fifth years, respectively. Cumulative 5-year incremental cost was US$3,633,440. Estimated incremental mean cost per treated patient with gout per year was US$112. The mean per-member per-month cost increased by US$0.06. Conclusion: Initiating lesinurad would result in an incremental per-member per-month cost of US$0.06 over 5 years.

Predictors of reaching a serum uric acid goal in patients with gout and treated with febuxostat.

PURPOSE: Clinical guidelines recommend febuxostat as first-line pharmacologic urate-lowering therapy for patients with gout to achieve a goal serum uric acid (sUA) <6 mg/dL; however, little is known about other contributing factors. This study identified clinical characteristics of patients treated with febuxostat to develop and validate a predictive model for achieving a goal sUA. PATIENTS AND METHODS: Patients with Humana Medicare or commercial insurance, diagnosed with gout and newly initiated on febuxostat (index date February 1, 2009 - December 31, 2013), were identified for a retrospective cohort study. Patients were followed for 365 days and the first valid sUA test result ≥120 days after index was retained. A stepwise logistic regression with backward elimination was estimated to model sUA goal attainment, and a linear model was estimated to model the impact of predictor variables on sUA level. RESULTS: The study sample (n=678) was divided into a development (training) dataset (n=453) and a validation (holdout) dataset (n=225). In the training sample, patients in the sUA <6 mg/dL group were on febuxostat for a longer time, were more adherent, and had a lower average base-line sUA level (all p<0.0001) vs patients in the sUA ≥6 mg/dL group. In the logistic model, febuxostat adherence (odds ratio [OR]=1.03, p<0.0001) and baseline sUA level (OR=0.84, p<0.0001) increased the odds of attaining sUA <6 mg/dL. In the linear regression model, increase in febuxostat adherence (p<0.0001), baseline sUA level (p<0.0001), advanced age (p=0.0021), and not having congestive heart failure (p<0.05) were associated with a reduction of sUA level. Pre-index allopurinol use was a marginally significant predictor of sUA level reduction (p=0.06). CONCLUSIONS: Among febuxostat users diagnosed with gout in a real-world setting, adherence to febuxostat and lower baseline sUA level were the strongest predictors of attaining sUA goal. These findings may help clinicians to identify appropriate patients most likely to benefit from febuxostat treatment, and underscore the importance of medication adherence in this challenging patient population.

The Challenges and Opportunities Associated with Reimbursement for Obesity Pharmacotherapy in the USA.

Obesity has become a serious public health problem that has stimulated primordial and primary prevention efforts, and a triad of management options (lifestyle, pharmacotherapy, and surgical interventions). A growing body of evidence supports the need for a multi-pronged, clinic-based approach that leverages the synergy between pharmaceutical and lifestyle modification. Recent US policy changes-namely, the passage of the Patient Protection and Affordable Care Act coupled with recognition of obesity as a disease by the American Medical Association-suggest that financial incentives and attitudes towards obesity management are changing. This paradigm shift has implications for current and future obesity pharmacotherapy. However, barriers to pharmacotherapy utilization include patient and physician perceptions of modest efficacy, historical safety issues, regulatory obstacles, and lack of reimbursement. The shifting attitudes and challenges associated not only with a multi-payer system, but also the lack of clearly defined cross-payer reimbursement strategies, prompted a survey to determine coverage for obesity treatment. Participants indicated that federal/state mandates and growth of quality-driven healthcare initiatives will eventually drive wider pharmacotherapy reimbursement within 1-5 years. There are signs that federal/state programs are already moving towards reimbursement by improving quality measures to track obesity outcomes and reduce costs. Future research on clinical and economic outcomes of combination weight-management programs coupled with innovative approaches (e.g., eHealth) in the real-world setting that demonstrate value to patients, healthcare providers, payers, and employers will help reshape obesity management by reducing barriers and broadening reimbursement coverage for anti-obesity pharmacotherapy.

Impact of thiazolidinedione safety warnings on medication use patterns and glycemic control among veterans with diabetes mellitus.

AIMS: In 2007, safety warnings were publicized regarding the association between thiazolidinediones (TZDs) and cardiovascular risks. This study investigated the impact of the publicized safety warnings on glycemic outcomes in patients with diabetes mellitus (DM). MATERIALS AND METHODS: The Veterans Integrated Services Network 16 database included 13,293 DM patients using TZDs (n=13,037 rosiglitazone, n=246 pioglitazone, n=10 both) during a baseline period of 03/01/07 to 05/31/07. Three medication use patterns groups (09/01/07 to 11/30/07) were defined as follows: (1) continuation on TZD treatment, (2) switching to other non-TZD treatment, (3) discontinuation of TZD treatment without any antidiabetic treatment. Primary outcome (09/01/07 to 02/29/08) was change from baseline in A1c. The analysis of variance was used to test the association between use patterns and A1c change. A logistic regression model was used to identify the predictors for use patterns. RESULTS: Patients (45.1%, n=5999) discontinued their TZD use. Both Groups 2 and 3 had significant A1c increases (both P values <.0001). Significant predictors for TZD discontinuation included black race, baseline heart disease, and diabetic complication [odds ratio (OR), 1.43; OR, 1.54; OR, 1.30, respectively]. Of the patients remaining on TZD therapy, 11.8% experienced improved A1c levels, and a lower percentage of patients (9.53%) experienced a deterioration in A1c levels (P<.0001). Patients who switched or discontinued an antidiabetic medication experienced improvements in body mass index (P<.0001) and triglycerides (P<.0036). The three use pattern groups had similar changes with regard to blood pressure and low-density lipoprotein. CONCLUSION: Thiazolidinedione safety warnings may have negatively impacted the glycemic control in DM patients.