Evaluation of Dipeptidyl Peptidase-4 Inhibitors versus Thiazolidinediones or Insulin in Patients with Type 2 Diabetes Uncontrolled with Metformin and a Sulfonylurea in a Real-World Setting.

BACKGROUND: Guidelines do not make clear recommendations for third add-on agents to metformin plus a sulfonylurea. This study compared the effectiveness and safety of dipeptidyl peptidase-4 inhibitors (DPP4is) to thiazolidinedione (TZD) or insulin as a third add-on agent to metformin plus a sulfonylurea in an integrated health care setting. METHODS: This retrospective database cohort study included adults with type 2 diabetes not at goal hemoglobin A1C (HbA1C) who initiated DPP4i, TZD, or insulin as a third add-on agent to metformin plus a sulfonylurea from January 2006 to June 2016. Primary outcomes were the proportion of patients who achieved goal HbA1C after starting the third add-on agent and change in HbA1C. Subgroup analysis was performed for patients with baseline HbA1C greater than 9%. RESULTS: In this study, 2080 patients started on a DPP4i were matched to 8320 patients started on TZD and to 8320 patients taking insulin. A significantly higher percentage of patients taking TZD reached goal HbA1C (31.0% versus 23.6%; p < 0.05) and had a significantly larger HbA1C reduction (-0.94% ± 1.34% versus -0.79% ± 1.23%; p < 0.01) compared to patients taking a DPP4i. No difference in the percentage of patients meeting goal HbA1C nor in change in HbA1C was demonstrated between insulin versus DPP4i regimens. For patients with baseline HbA1C greater than 9%, insulin or TZD resulted in a significantly higher proportion of patients achieving goal HbA1C compared to DPP4i (17.3% and 19.0% versus 12.4%, respectively; p < 0.01). CONCLUSION: TZD was more effective than DPP4i but DPP4i was as effective as insulin as a third add-on agent in the overall study population. Insulin was more effective than DPP4i only in the subgroup analysis of patients with baseline HbA1C greater than 9%.

Evaluation of Outcomes After Initiating Triple Antidiabetic Therapy with a GLP-1 RA in an Integrated Health Care System.

BACKGROUND: Type 2 diabetes (T2D) is characterized by chronic hyper-glycemia and can lead to life-threatening complications if not treated. A stepwise and patient-centered approach is recommended when managing patients with T2D. Metformin is the preferred first-line agent, while sulfonylureas (SU) are often chosen as second-line agents. If a patient's hemoglobin A1c (A1c) goal is not achieved despite 3 months of treatment with dual therapy, then triple therapy is recommended. However, due to the lack of head-to-head trials for different triple antidiabetic regimens, the recommendations are unclear for selection of an optimal third-line agent. OBJECTIVE: To evaluate the comparative effectiveness of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) compared with a thiazolidinedione (TZD) or insulin as a third-line add-on therapy in patients who have not achieved A1c goals while receiving metformin and SU dual therapy in the real-world setting within an integrated health care system. METHODS: This is a retrospective cohort study of adult patients with T2D who were not at goal A1c while on dual therapy with metformin and an SU and initiated triple antidiabetic therapy. The primary outcome was the proportion of patients who achieved goal A1c within 3-7 months after starting triple therapy with a GLP-1 RA compared with a TZD or insulin. Goal A1c was defined as an A1c of < 7% for patients aged less than 65 years and A1c of < 8% for patients aged 65 years or older. Secondary outcomes included mean change in A1c, mean change in weight, and the proportion of patients with an emergent health care encounter due to a hypoglycemic event. Propensity score matching was used to select comparison groups from the insulin and TZD groups with similar baseline characteristics to the GLP-1 RA group in a 4:1 ratio. RESULTS: 274 patients initiated a GLP-1 RA in addition to dual therapy with metformin and an SU. A propensity matched group of 1,096 patients who initiated insulin and 1,096 patients who initiated a TZD were selected as the control groups. Addition of a GLP-1 RA resulted in a significantly lower proportion of patients achieving goal A1c (23.0%) compared with the addition of a TZD (30.8%, P = 0.011). There was no significant difference with the addition of a GLP-1 RA when compared with insulin (24.1%, P = 0.704). CONCLUSIONS: This study reflects data from real-world practice in a large integrated health care system. Significantly less patients achieved goal A1c with the addition of a GLP-1 RA as a third-line add-on option to dual therapy with metformin and an SU compared with the addition of a TZD. Providers and patients should carefully weigh the risks and benefits of different antidiabetic agents when choosing triple therapy regimens. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. Part of this study was presented as a nonreviewed resident poster at the Academy of Managed Care & Specialty Pharmacy Annual Meeting 2017 in Denver, CO, on March 27-29, 2017.

Treatment Patterns and Overall Survival Associated with First-Line Systemic Therapy for Patients with Advanced Non-Small Cell Lung Cancer.

BACKGROUND: A variety of regimens are used as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC), which may include combination regimens and single agents, depending on histology, molecular profile, and performance status. OBJECTIVE: To describe the types of first-line therapies and compare overall survival between therapies used for patients with advanced NSCLC in an integrated health care system. METHODS: This retrospective cohort study included patients aged 18 years or older from Kaiser Permanente California with a diagnosis of stage IIIB/IV NSCLC. First systemic treatment date occurred from January 1, 2008, through September 30, 2013. Overall survival was measured as the number of months from initial treatment until death, end of enrollment, or September 30, 2014. Treatment regimens were categorized into 6 mutually exclusive groups: platinum doublets; pemetrexed-based, bevacizumab-based, and pemetrexed + bevacizumab-based combinations; singlets; and tyrosine-kinase inhibitors (TKIs). Survival was compared using Kaplan-Meier curves and adjusted Cox proportional hazard models. Subgroup analyses were performed by age group and by nonsquamous histology. RESULTS: Of 2,081 patients, approximately half (52.3%) received platinum doublets, followed by TKIs (19.0%), pemetrexed-based regimens (13.4%), bevacizumab-regimens (8.0%), singlets (5.5%), and pemetrexed + bevacizumab-based combinations (1.8%). Median survival was longest for pemetrexed + bevacizumab-based combinations (18.5 months), followed by bevacizumab-based regimens (14.5), TKIs (12.7), pemetrexed-based regimens (10.4), doublets (9.2), and singlets (5.3). There was a significantly reduced risk of mortality for pemetrexed + bevacizumab-based combinations (HR = 0.64; 95% CI = 0.42-0.94) and TKIs (HR = 0.83; 95% CI = 0.73-0.94) compared with doublets. Singlets were associated with an increased risk of mortality (HR = 1.50; 95% CI = 1.22-1.84). Subgroup analysis among patients aged 65 years and over found no significant differences among treatment groups, with the exception of singlets, which were associated with an increased risk of mortality compared with doublets (HR = 1.51; 95% CI = 1.20-1.90). Among patients under aged 65 years, pemetrexed + bevacizumab-based combinations (HR = 0.36; 95% CI = 0.21-0.64) and TKIs (HR = 0.76; 95% CI = 0.59-0.97) were associated with a reduced risk of mortality, and singlets were associated with an increased risk (HR = 1.85; 95% CI = 1.17-2.92). CONCLUSIONS: In this cohort of patients with advanced NSCLC, patients received a platinum agent with or without bevacizumab or pemetrexed, a TKI, or a single agent. Younger patients (aged < 65 years) receiving bevacizumab + pemetrexed-based combinations had a survival advantage over those receiving platinum doublets, and this finding merits further investigation. Younger patients receiving TKIs also had longer survival. Compared with platinum doublets, we found no survival advantage for older patients receiving bevacizumab or pemetrexed, which suggests that combination therapy of a platinum agent and taxane, such as carboplatin and paclitaxel, could be a reasonable option for older patients who are not candidates for targeted therapy. DISCLOSURES: No outside funding supported this study. Rashid has received past funding from Bristol-Myers Squibb, Astellas, Novartis, and Pfizer. No other authors report any potential financial conflicts of interest. Study concept and design were primarily contributed by Spence and Hui, with input from the other authors. Hui, Spence, and Rashid took the lead in data collection, and data interpretation was performed by Schottinger, Millares, and Spence, assisted by the other authors. The manuscript was written primarily by Spence, along with Chang, and revised by Spence, with input from the other authors.

Identifying Subsequent Therapies in Patients with Advanced Non-Small Cell Lung Cancer and Factors Associated with Overall Survival.

STUDY OBJECTIVES: To identify subsequent therapies used after first-line therapies in patients with advanced non-small cell lung cancer (NSCLC), compare overall survival (OS) associated with subsequent therapies, and evaluate factors associated with OS in these patients. METHODS: The study was a retrospective cohort analysis of patients with advanced NSCLC (stage IIIB/IV) who were initiated on first-line therapy from January 1, 2008, through September 30, 2013, and afterward given subsequent chemotherapy (index date). Patients had to be 18 years or older at the time of diagnosis of advanced NSCLC. Patients were followed from the index date until one of the following end points: end of the study (September 30, 2014), disenrollment from the health plan, or death-whichever came the earliest. The primary outcome was OS. Kaplan-Meier curves and Cox proportional hazard models were used to analyze OS and evaluate the factors associated with OS. RESULTS: The analysis included 1280 patients on subsequent therapies. The most common subsequent therapies were pemetrexed (284 patients [22%]), erlotinib (216 patients [17%]), and docetaxel (139 patients [11%]). Patients from the singlets group had a lower OS at 6.3 months compared with all other groups: pemetrexed based, combination of pemetrexed and bevacizumab based, bevacizumab based, doublets, and tyrosine kinase inhibitors (p<0.0001). Factors associated with greater OS included age younger than 65 years, female gender, and a longer time between initiation of first and subsequent therapies. Factors associated with a reduction in OS were pemetrexed-based or singlet regimens for subsequent therapy, diagnosis of squamous histology, and a higher number of adverse events prior to subsequent therapy. CONCLUSION: We found that a subsequent therapy consisting of singlets is associated with reduced OS compared with other chemotherapy groups. Patient characteristics such as female gender, age younger than 65 years, diagnosis of nonsquamous histology, and/or a longer time frame between initiation of first-line and subsequent chemotherapy are associated with longer survival.

Association between exposure to topical tacrolimus or pimecrolimus and cancers.

BACKGROUND: The Food and Drug Administration has issued a public health advisory regarding cancer risk from topical calcineurin inhibitors. OBJECTIVE: To compare the rates of cancer among patients with common dermatologic conditions who were exposed or not exposed to topical calcineurin inhibitors. METHODS: A retrospective cohort observational study used data from an integrated healthcare delivery system on 953,064 subjects with diagnoses of atopic dermatitis or eczema between 2001 and December 2004. The main endpoint was initial cancer diagnosis. Chart review was performed to confirm cancer diagnosis in the subjects exposed to topical calcineurin inhibitors when any particular cancer rate was at least 3 times higher than that in unexposed subjects. Data were analyzed using the Cox proportional hazards model. RESULTS: Age- and sex-adjusted hazard ratios for all cancers were 0.93 (95% CI 0.81 to 1.07; p = 0.306) for tacrolimus-exposed versus -unexposed subjects and 1.15 (95% CI 0.99 to 1.31; p = 0.054) for pimecrolimus-exposed versus -unexposed subjects. T-cell lymphoma was the only cancer associated with a significantly increased risk among subjects exposed to tacrolimus (HR = 5.04, 95% CI 2.39 to 10.63; p < 0.001) or pimecrolimus (HR = 3.76, 95% CI 1.71 to 8.28; p = 0.010). Subsequent chart review of subjects in the exposed group with T-cell lymphoma found that 4 of 16 had skin lesions that were suspected to be the early lesions of T-cell lymphoma prior to exposure to tacrolimus or pimecrolimus. After these 4 cases were excluded, the age and sex hazard ratio for T-cell lymphoma was 5.44 (95% CI 2.51 to 11.79; p < 0.001) for tacrolimus and 2.32 (95% CI 0.89 to 6.07; p = 0.086) for pimecrolimus. There was no statistically significantly increased risk for other subgroups of cancer, including melanoma. CONCLUSIONS: Exposure to topical tacrolimus or pimecrolimus was not associated with an increase in the overall cancer rate. Use of topical tacrolimus may be associated with an increased risk of T-cell lymphoma.

Kaiser Permanente's evaluation and management of biotech drugs: assessing, measuring, and affecting use.

Two decades into the age of high-cost biotechnology medications, health care organizations are challenged to provide safe, effective treatment while managing costs. In a market lacking generic biotech drugs, health care organizations have few opportunities to negotiate reduced pricing; other strategies must be devised to manage use. Kaiser Permanente leverages its integrated health care delivery system to deploy management tools for costly therapies: evidence analysis, usage measurements, and multidisciplinary planning. Evidence-based medicine and realization of value provided by new therapies will depend on data capture and outcomes measurement, tools that are crucial to Kaiser Permanente's management of biotechnologies and effective use of members' financial resources.

Direct-to-consumer advertising of COX-2 inhibitors: effect on appropriateness of prescribing.

Spending on direct-to-consumer advertising (DTCA) of prescription drugs has increased dramatically in the past several years. An unresolved question is whether such advertising leads to inappropriate prescribing. In this study, the authors use survey and administrative data to determine the association of DTCA with the appropriate prescribing of cyclooxygenase-2 (COX-2) inhibitors for 1,382 patients. Treatment with either a COX-2 or a traditional nonsteroidal anti-inflammatory drug (NSAID) was defined as appropriate or not according to three different definitions of gastrointestinal risk. Patients who saw or heard a COX-2 advertisement and asked their physician about the advertised drug were significantly more likely to be prescribed a COX-2 (versus a NSAID, as recommended by evidence-based guidelines) than all other patients. Findings also suggest that some patients may benefit from DTCA. The authors discuss the need for balanced drug information for consumers, increased physician vigilance in prescribing appropriately, and further study of DTCA.