Correction to: Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT.

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Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT.

BACKGROUND: To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs. METHODS: Patients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests. RESULTS: Data from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients (both doses, P < 0.05) reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients. CONCLUSIONS: Upadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs.

BACKGROUND: Patient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR). METHODS: PRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated. RESULTS: In 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients. CONCLUSIONS: In bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.

Economic Burden of Patients with Inadequate Response to Targeted Immunomodulators for Rheumatoid Arthritis.

BACKGROUND: Targeted immunomodulators (TIMs), including biologic disease-modifying antirheumatic drugs (DMARDs) and JAK/STAT inhibitors, are effective therapies for rheumatoid arthritis (RA), but some patients fail to respond or lose response over time. This study estimated the real-world prevalence of RA patients with inadequate responses to an initial TIM (nonresponders) in the United States and assessed their direct and indirect economic burden compared with treatment responders. METHODS: Administrative claims data (January 1999-March 2014) from a large private-insurer database were used, which included work-loss data from a subset of reporting companies. Eligible patients (classified as responders and nonresponders) had ≥ 1 claim for a TIM approved for the treatment of RA and ≥ 2 RA diagnoses in the claims history, with continuous pharmaceutical and medical benefit eligibility for 6 months before (baseline) and 12 months after (study period) the date of the first TIM claim (index date). All-cause and RA-related health care resource use (HCRU) and costs, work loss, and indirect costs during the study period were compared for responders versus nonresponders. Multivariable regression was used to adjust for baseline covariates. Sensitivity analyses of HCRU and direct costs were conducted for patients with index dates before and after 2008 to account for different approval dates of TIMs. RESULTS: Of 7,540 eligible patients with RA, 2,527 (34%) were classified as responders, and 5,013 (66%) were classified as nonresponders; 407 and 723 had work-loss data, respectively. After adjusting for baseline covariates, nonresponders had significantly higher HCRU, including inpatient admissions (incidence rate ratio [IRR] = 1.94), outpatient visits (IRR = 1.19), emergency department visits (IRR = 1.53), and number of prescription fills (IRR = 1.09; all, P < 0.001). Nonresponders also had significantly higher adjusted all-cause ($12,868 vs. $9,621, respectively) and RA-related ($5,740 vs. $4,495; both, P < 0.001) medical costs compared with responders. In addition, nonresponders reported significantly more days of work lost compared with responders (22.1 vs. 16.7 days, respectively; IRR = 1.21; P = 0.007) and higher indirect costs ($3,548 vs. $2,890; P = 0.002). Sensitivity analyses of HCRU and direct costs by index date (before and after 2008) were consistent with the full sample. CONCLUSIONS: A large portion of patients with RA had inadequate responses to their initial TIM therapy with significantly higher economic burden, including higher HCRU, medical costs, and indirect costs due to work loss, compared with TIM therapy responders. DISCLOSURES: Funding for this research was provided by AbbVie, which was involved in all stages of the study research and manuscript preparation. Tundia and Fuldeore are employed by AbbVie. Song and Macaulay are employed by Analysis Group, which received grants from AbbVie to conduct this study. Strand reports grants and personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Celltrion, Corrona, Crescendo, Genentech/Roche, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, and UCB outside the submitted work. Study concept and design were contributed by Tundia, Song, and Macaulay, along with other authors. Data analyses were designed and conducted by Song and Macaulay. All authors contributed to data interpretation. Writing of the manuscript was led by Tundia, Song, and Macaulay, with revisions by all authors. A synopsis of the current research was presented at the American College of Rheumatology/Association of Rheumatology Health Professionals meeting, which took place in Washington, DC, during November 11-16, 2016.

Impact of uterine fibroid symptoms on health-related quality of life of US women: evidence from a cross-sectional survey.

BACKGROUND: Uterine fibroids (UF) are associated with significant health-related quality of life (HRQL) impact. This study examined the impact of UF symptoms on HRQL. METHODS: An online cross-sectional survey of 18 to 49 year old US women was conducted and collected demographics, UF prevalence, symptoms, and HRQL using the UFS-QOL. Descriptive statistics were used to examine the impact of symptom presence, severity, bothersomeness, and number of UF symptoms on HRQL. Analyses were weighted to match the US female population distribution. Multivariate regressions were performed with each subscale as a dependent variable to examine the impact of individual UF symptoms on HRQL. RESULTS: A total of 59,411 (15.5%) panel members completed the prevalence screener; 4848 met inclusion criteria; 955 had UF and no hysterectomy. Mean age was 40.3; 58% were white; 63% were married/civil union. Common UF symptoms were: lower back pain (65%), fatigue/weariness (63%), bloating (61%), pelvic pain/cramping during menses (63%), and heavy bleeding during menses (54%). Mean UFS-QoL subscale scores were significantly (p < .05) worse among women with a UF symptom versus women without the symptom. Women who rated their UF symptoms as severe had significantly (p < .001) worse UFS-QoL scores than women with mild or moderate symptoms. UFS-QoL subscale scores worsened as the number of symptoms increased. In the regressions, the presence of bleeding and non-bleeding symptoms were related to worse UFS-QoL subscale scores. CONCLUSION: HRQL among women with UF was significantly impacted by UF-related symptoms. Greater impact was observed as the number and severity of symptoms increased.

The burden of endometriosis symptoms on health-related quality of life in women in the United States: a cross-sectional study.

INTRODUCTION: To examine the symptomatic burden of endometriosis on health-related quality of life (HRQL) in women in the United States (US). METHODS: A cross sectional web-based survey study was conducted among women using survey panels. The survey included study-specific questions and standardized HRQL questionnaires. Participants reviewed a list of endometriosis symptoms and selected all symptoms they had ever or were currently experiencing. For current symptoms, participants rated the severity and bothersomeness of each symptom. Participants completed the endometriosis health profile (EHP-30) core questionnaire. Descriptive analyzes were performed and multivariate regressions were run with each EHP subscale as a dependent variable to examine the impact of symptoms while controlling for age and comorbid conditions. RESULTS: Mean age of the 1269 women was 34.3 ± 0.3; 78% were white. At least 75% reported having ever experienced: pelvic pain/cramping during their menstrual period, anxiety/stress, lower back pain or fatigue/weariness/anemia. EHP-30 scores ranged from 33.6 (95% CI: 31.4, 35.8) (social support) to 37.8 (95% CI: 35.5, 40.1) (control and powerlessness), indicating moderate HRQL impact. For all but one domain and one symptom, EHP-30 scores were significantly higher (worse) for women who had individual endometriosis-related symptoms than for those who did not. EHP-30 scores consistently deteriorated with each increase in the number of symptoms experienced and by increasing perceived disease severity. Pelvic pain/cramping during menstrual period, irregular periods and general abdominal pain were significantly associated with the EHP-30 domain scores in the regression models. CONCLUSION: Experiencing endometriosis symptoms is associated with lower HRQL. Importantly, as symptom severity and number of symptoms increase, HRQL further deteriorates.

Patient-reported prevalence and symptomatic burden of uterine fibroids among women in the United States: findings from a cross-sectional survey analysis.

PURPOSE: To estimate the prevalence of women diagnosed with uterine fibroids and the associated symptom burden in the US. PATIENTS AND METHODS: Responses of women aged 18-54 years, who completed an online survey, were analyzed. Data were weighted based on age, education, race, geographic region, income, and propensity score to derive national estimates of the prevalence of women diagnosed with uterine fibroids and associated symptom burden. Weighted means and percentages were reported. Prevalence across age and ethnic groups was examined. Symptom burden among women with and without uterine fibroids was compared using weighted logistic regressions. RESULTS: Of 59,411 respondents who met study inclusion criteria, 7.7% reported receiving a diagnosis of uterine fibroids. Of these, 5,670 women (1,402 in the uterine fibroid group and 4,268 in the control group) were excluded from analysis because they had a hysterectomy. Among the non-hysterectomized study participants, 3,031 self-reported a diagnosis of uterine fibroids (prevalence: 5.8%, 95% confidence interval [CI]: 5.5%-6.1%); prevalence increased as women aged and was greatest in the 50-54 age group (11.4%; 95% CI: 10.4%-12.4%). In addition, prevalence was greater in black vs white women (9.8%; 95% CI: 8.7%-11.0% vs 5.4%; 95% CI: 5.1%-5.7%). A greater percentage of women with uterine fibroids (vs those without) experienced severe heavy menstrual bleeding (16.7% vs 7.7%), severe constipation/bloating/diarrhea (7.7% vs 4.7%), severe passage of clots (6.7% vs 2.4%), severe spotting/bleeding between periods (1.7% vs 1.0%), and severe pelvic pressure (1.6% vs 0.6%). Among uterine fibroid patients with these typical uterine fibroid-related symptoms, 56.4%, 32.3%, 26.4%, 25.8%, and 20.4% reported heavy menstrual bleeding, passage of clots, spotting/bleeding between periods, constipation/bloating/diarrhea, and pelvic pressure, respectively, as extremely bothersome. CONCLUSION: Uterine fibroids impose a heavy burden on women aged 18-54 years in the US.

Factors Associated with Time to Endometriosis Diagnosis in the United States.

BACKGROUND: We aimed to quantify the time to diagnosis among women with endometriosis in the United States (US) and to identify patient- and physician-related factors affecting diagnostic delay. PATIENTS AND METHODS: An online cross-sectional survey was conducted from August 6, 2012, through November 14, 2012. Respondents aged 18-49 years who reported a physician's diagnosis/suspicion of endometriosis within the previous 10 years were included. Endometriosis-related symptoms and diagnostic history were captured and summarized. Univariate analyses identified factors associated with time from symptom onset to first consultation and from first consultation to diagnosis. RESULTS: Of 638 respondents included, most (56%) reported seeking care for at least one of the following symptoms: menstrual pain (31.6%), nonmenstrual pain (27.3%), and pain during sex (7.5%). Most diagnoses (84%) were made by obstetricians/gynecologists; 49% of diagnoses were surgical versus 51% nonsurgical. Mean time from symptom onset to diagnosis was 4.4 years. Mean time to first consultation was shorter among women aged 40-49 years versus those aged <18 years (14.2 vs. 43.5 months; p < 0.0001) and those consulting for symptoms versus routine/other care (27.9, 24.9, and 28.4 months for menstrual pain, nonmenstrual pain, and pain during sex, respectively, vs. 61.4 months; all p < 0.01). Mean time from first consultation to diagnosis was shorter among women aged 40-49 years versus those aged <18 years (12.4 vs. 34.5 months; p = 0.0009) and those diagnosed by obstetricians/gynecologists versus nonobstetricians/gynecologists (21.5 vs. 40.3 months; p = 0.041). CONCLUSIONS: Time to endometriosis diagnosis appears to have shortened in the US. Better patient and physician education regarding symptomatology may contribute to further gains.

Prevalence and Symptomatic Burden of Diagnosed Endometriosis in the United States: National Estimates from a Cross-Sectional Survey of 59,411 Women.

BACKGROUND/AIMS: To estimate the prevalence of diagnosed endometriosis (DE) in women in the United States and assess the associated symptomatic burden. METHODS: An online, cross-sectional survey of women aged 18-49 years was conducted from August 6, 2012, through November 14, 2012. Survey data (weighted by age, race, education, income, geographical distribution, and propensity score) were used to estimate the prevalence and symptomatic burden of DE in women in the United States. Weighted logistic regressions were used to assess differences in symptom burden between women with and without endometriosis. RESULTS: The prevalence of DE was estimated at 6.1% (2,922 of 48,020 women surveyed); 52.7% of women were 18-29 years of age when they were diagnosed with endometriosis. Most (86.2%) women experienced symptoms before diagnosis. More women with (vs. without) DE had menstrual pelvic pain/cramping (52.7 vs. 45.2%), non-menstrual pelvic pain/cramping (36.7 vs. 14.3%), infertility (11.6 vs. 3.4%), and dyspareunia (29.5 vs. 13.4%). Women with endometriosis were also more likely to report severe symptoms (OR (95% CI) 2.7 (2.3-3.1) for menstrual pelvic pain/cramping, 2.2 (1.7-2.9) for non-menstrual pelvic pain/cramping, and 2.4 (1.8-3.2) for dyspareunia). CONCLUSION: The prevalence of DE among US women is notable, and affected women experience a substantial symptom burden.

Direct Costs in Patients with Celiac Disease in the USA: A Retrospective Claims Analysis.

BACKGROUND: Celiac disease (CeD) is an autoimmune disease triggered by gluten ingestion. AIM: We assessed total direct costs burden associated with CeD in patients with CeD versus patients without CeD using administrative claims data. METHODS: Patients with CeD (cases) with ≥1 occurrences of CeD diagnosis were selected at a randomly chosen date (index date) from the OptumHealth Reporting and Insights database from 01/01/1998 through 03/31/2013. Cases were continuously enrolled throughout baseline (1 year before index date) and study (1 year after index date) periods. Cases were categorized as full remission and partial remission and matched 1:1 based on age, sex, region, index date, company, and employment status. Total all-cause and CeD-related costs were calculated. RESULTS: A total of 12,187 cases were matched with an equal number of controls. Mean total all-cause costs were $12,217 in cases versus $4935 in controls (P < 0.0001). In full remission (N = 10,181 [83.5 %]) and partial remission (N = 2006 [16.5 %]) cases, mean total all-cause direct costs (cases versus controls) were $11,038 versus $4962 and $18,206 versus $4796, respectively. All-cause medical costs ($9839 for all cases, $8723 for full remission cases, $15,499 for partial remission cases) accounted for the majority of all-cause total costs and included outpatient costs ($6675; $6456; and $7785, respectively) and hospitalizations ($2776; $1963; and $6906, respectively). CeD-related medical costs were 13 and 27 % of all-cause medical costs for all cases and partial remission cases, respectively. CONCLUSIONS: Patients with CeD and partial remission of CeD incurred significantly higher (2.5 and 3.8 times) total all-cause costs compared with matched controls.

Efficacy and Safety of Pancrelipase/Pancreatin in Patients With Exocrine Pancreatic Insufficiency and a Medical History of Diabetes Mellitus.

OBJECTIVES: The aim of this study was to perform exploratory analyses of the efficacy and safety of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency (EPI) with (n = 36) and without (n = 18) concurrent diabetes mellitus (DM). METHODS: This was a retrospective, post hoc, subgroup (±DM) analysis of a double-blind, randomized, placebo-controlled trial of pancrelipase in patients with EPI due to chronic pancreatitis or pancreatectomy (total or partial). After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units/meal, 36,000/snack) or placebo for 7 days. Outcomes included changes in coefficients of fat absorption (CFA) and nitrogen absorption (CNA) from baseline to the end of the double-blind period. RESULTS: Mean changes in nutrient absorption were greater with pancrelipase versus placebo in patients with DM (CFA, 36.0% vs 7.5%, P < 0.0001; CNA, 33.4% vs 3.7%, P = 0.0002) and without DM (CFA, 25.2% vs 12.3%, P = 0.0326; CNA, 39.1% vs 17.6%, P = 0.1187). Diabetes mellitus was not significantly associated with outcomes for CFA (P = 0.0802) and CNA (P = 0.2934). Incidences of adverse events, including hypoglycemia and hyperglycemia, were similar in the pancrelipase and placebo arms. CONCLUSIONS: Pancrelipase improved fat and protein absorption in patients with EPI due to chronic pancreatitis or pancreatectomy, with or without DM, and matched the safety profile previously reported.

Healthcare utilization and costs among women diagnosed with uterine fibroids: a longitudinal evaluation for 5 years pre- and post-diagnosis.

OBJECTIVE: To evaluate the healthcare utilization, treatments, and costs incurred by women with uterine fibroids (UF), compared to those without UF, for 5 years before and 5 years after diagnosis. RESEARCH DESIGN AND METHODS: This is a longitudinal, retrospective case-control study. A total of 84,954 women with a diagnosis of UF, along with matched controls of women without UF, were selected from the Truven Health MarketScan claims database (2000-2010). The date of diagnosis of the UF patient was assigned as the index date for both the UF patient and her matched control. MAIN OUTCOME MEASURES: Healthcare resource utilization, treatments, and costs (in 2010 USD) were evaluated annually for the 5 year periods before and after the index date. RESULTS: UF patients had more outpatient and emergency room visits than controls before diagnosis, and more inpatient, outpatient, and emergency room visits than controls after diagnosis. Annual total healthcare costs were significantly higher for patients than controls during the last 3 years pre-index and all 5 years post-index. Overall, the difference was $12,623 over 10 years, with a difference of $1435 in the 5 years pre-diagnosis and a difference of $11,188 in the 5 years post-diagnosis. The cost difference between UF patients and controls was highest in the first year post-diagnosis, reaching $6131, and the difference was even larger when comparing clinically symptomatic UF patients to controls. The use of medications and surgical procedures related to UF peaked in the year post-diagnosis, with 39% of patients receiving a surgical treatment within the year. KEY LIMITATIONS: UF patients included in the study did not include undiagnosed and potentially asymptomatic UF patients; the impact of disease severity on the costs of UF patients was not evaluated. CONCLUSIONS: Patients with UF incurred significantly higher healthcare utilization and costs than those without UF, both pre- and post-diagnosis.

Healthcare utilization and costs in women diagnosed with endometriosis before and after diagnosis: a longitudinal analysis of claims databases.

OBJECTIVE: To assess healthcare resource utilization and costs during the 5 years before and 5 years after diagnosis among women with endometriosis, in comparison with women without endometriosis. DESIGN: Longitudinal, retrospective, case-control study. SETTING: None. PATIENT(S): A total of 37,570 matched pairs of women with and without (controls) endometriosis were identified from the Truven Health MarketScan claims database (2000-2010). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Annual healthcare resource utilization and costs (in 2010 US dollars) were evaluated for the 5 years before and 5 years after diagnosis. RESULT(S): Mean patient age at index (first diagnosis) date was 36.4 years for endometriosis patients and controls. Endometriosis patients had a higher utilization of outpatient and emergency room services during each pre- and postindex year, and a higher utilization of inpatient services during the last preindex year and all 5 postindex years. Total costs were highest in the first postindex year for endometriosis patients, reaching $13,199, compared with $3,747 for controls. Annual costs were significantly higher for patients than controls during each pre- and postindex year; overall, the cost difference was $26,305 over 10 years: $7,028 in the 5 years before diagnosis and $19,277 in the 5 years after diagnosis. CONCLUSION(S): Endometriosis poses a significantly high economic burden, both before and after diagnosis. The highest resource utilization and costs experienced by endometriosis patients occur in the first year after diagnosis.

Temporal trends and predictors of salvage cancer treatment after failure following radical prostatectomy or radiation therapy: an analysis from the CaPSURE registry.

BACKGROUND: Prostate cancer treatment after failure of primary therapy by either radical prostatectomy or radiation therapy can vary greatly. This study sought to determine trends and predictors of salvage treatment after failure of primary treatment in a community cohort over the past 10 years. METHODS: From the community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, 6275 patients were identified who initiated a form of primary treatment for prostate cancer; 839 of these were identified as failing treatment by biochemical recurrence or initiation of secondary treatment between 2000 and 2010. Salvage therapy was categorized as either systemic, local, or none. Patient characteristics were tested for association with salvage therapy using analysis of variance, Pearson chi-square tests, and multinomial logistic regression analysis. RESULTS: Of the 839 patients identified as failing therapy, 390 (47%), 146 (17%), and 303 (36%) received systemic, local, or no salvage therapy, respectively. Type of primary treatment received was associated with type of salvage therapy (P < .01). There has been an increasing trend in the use of local salvage therapy over the past 10 years (P = .04). Primary treatment type and biopsy Gleason score were significantly associated with type of salvage therapy. CONCLUSIONS: The use of local salvage therapy has increased over the past decade, whereas the use of systemic salvage therapy has declined. Primary treatment is an important factor in determining which type of salvage therapy a patient will receive.

Patient demographics, quality of life, and disease features of men with newly diagnosed prostate cancer: trends in the PSA era.

OBJECTIVE: To describe how demographic and diagnostic characteristics of men with prostate cancer in the United States have changed since 1999, using data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. METHODS: The medical records of patients enrolled in CaPSURE between 1999 and 2011 were evaluated. Baseline demographics, disease features, and imaging use were assessed. Mantel-Haenszel chi-square was used to test for trends across diagnostic years. RESULTS: Between 1999 and 2011, a total of 9572 patients were diagnosed with prostate cancer and enrolled in CaPSURE at community (36), academic (3), and Veteran's Affairs (4) hospitals. Over the study period, mean age at diagnosis decreased, P <.01. In 2008-2011, a significant increase in diagnostic Gleason 7 or higher was observed relative to 1999-2001 (50% vs 36%, P <.01), congruent with recent guideline modifications of the Gleason classification system. An increase in the mean number of diagnostic biopsy cores (13.3 vs 8.3, P <.01) was also observed. A significant decrease in use of any imaging modality was seen (19% vs 45%, P <.01). Average pretreatment urinary and bowel function scores did not change, although there were significant increases in sexual function observed overall (P <.01). CONCLUSION: In the United States, several trends in the demographics and disease profile of men with newly diagnosed prostate cancer were observed over the past 12 years. Decreased imaging use and increased number of cores taken during diagnostic biopsy are in line with national urologic guidelines on prostate cancer diagnosis and management.

Elagolix, an Oral GnRH Antagonist for Endometriosis-Associated Pain: A Randomized Controlled Study.

OBJECTIVE: The aim of this study was to estimate the efficacy of elagolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of endometriosis-associated pelvic pain. METHODS: This was a phase II, randomized, placebo-controlled parallel group study conducted at 37 US centers, consisting of an 8-week double-blind period followed by a 16-week open-label period. Patients were 137 women aged 18 to 49, with laparoscopically confirmed endometriosis and moderate to severe nonmenstrual pelvic pain and dysmenorrhea, who were administered elagolix 150 mg daily or placebo. The primary outcomes of the study were the daily assessment of dysmenorrhea, nonmenstrual pelvic pain and dyspareunia using a modified Biberoglu-Behrman scale. RESULTS: During the double-blind period, there were significantly greater mean reductions from baseline to week 8 in dysmenorrhea (-1.13 ± 0.11 vs. -0.37 ± 0.11, p<0.0001), nonmenstrual pelvic pain (-0.47 ± 0.07 vs. -0.19 ± 0.07, p = 0.0066), and dyspareunia scores (-0.61 ± 0.10 vs. -0.23 ± 0.10, p = 0.0070) in the elagolix group compared with placebo. Continued improvements were observed during the open-label treatment regardless of initial treatment allocation. Elagolix treatment was also associated with significant improvements in quality-of-life measures during the double-blind and open-label periods. The most common adverse events occurring with elagolix were nausea, headache and hot flush, each in 9.9% of patients. CONCLUSION: Elagolix effectively reduced endometriosis-associated pelvic pain over a 24-week period and was well-tolerated.

Medical resource use and costs related to central precocious puberty: a retrospective cohort study.

OBJECTIVE: To evaluate the economic burden of central precocious puberty (CPP) by examining direct health care resource utilization and costs. METHODS: Administrative claims from the Medstat MarketScan Commercial Claims database were analyzed, and 2 cohorts of children ≤ 12 years of age were identified. The CPP cohort included patients newly diagnosed with precocious sexual development and puberty (International Classification of Diseases, Ninth Revision, Clinical Modification code 259.1x) between January 1, 2004, and June 30, 2006 (date of the initial diagnosis of CPP was designated as the "index date") who used gonadotropin-releasing hormone agonists during the 12 months after diagnosis. Each patient with CPP was matched with 4 control patients without CPP on the basis of age, sex, geographic region, and type of health insurance plan. Resource utilization and costs during the 12 months before and the 12 months after the index date were examined. RESULTS: A total of 172 patients with CPP and 688 control patients were identified after matching. Approximately 62% of patients were 7 to 9 years of age, and 87% were female. The patients with CPP had higher annual health care costs than did the control patients during the 12-month pre-index ($10,968 versus $783; P<.001) and the 12-month post-index ($21,071 versus $849; P<.001) periods, primarily attributable to outpatient and pharmacy costs. For the patients with CPP, annual health care costs increased by $10,103 after diagnosis. On average, annual CPP-related costs were $10,605. Monthly total health care costs for the patients with CPP increased sharply during the first month after diagnosis and remained high throughout the post-index period. CONCLUSION: In this study, health care resource use and costs among patients with CPP were substantial before and after the initial diagnosis of CPP.

Chronic kidney disease in gout in a managed care setting.

BACKGROUND: To study the prevalence of chronic kidney disease (CKD) and its impact on allopurinol dosing and uric acid control among patients with gout. METHODS: This was a retrospective study using data from a large US health plan. Claims and laboratory data were analyzed for enrollees from the health plan database from January 2002 through December 2005. Patients with gout were identified from pharmacy and medical claims data based on the presence of codes for gout medication or gout diagnosis. Severity of CKD was determined using the estimated glomerular filtration rate (eGFR). Allopurinol titration was defined as a change in average daily dose from first prescription to last prescription of ≥ 50 mg. RESULTS: A total of 3,929 patients were identified for inclusion in this study, 39% of whom had CKD (based on having an eGFR < 90 mL/min/1.73 m2). Subjects with CKD were older (p < 0.01) and more likely to be women (p < 0.01), had a greater number of comorbid conditions (p < 0.01), and were more likely to be prescribed allopurinol (p < 0.01) compared to those with no CKD. The average starting dose of allopurinol was lower among those with CKD, and it decreased with worsening kidney function. Among the 3,122 gout patients who used allopurinol, only 25.6% without CKD and 22.2% with CKD achieved a serum uric acid concentration of < 6.0 mg/dL (p = 0.0409). Also, only 15% of allopurinol users had an upward dose titration (by ≥50 mg), but the average increase in dose did not differ significantly between those with and without CKD. CONCLUSIONS: About two out of every five patients with gout in this population had CKD. Allopurinol doses were not adjusted in the majority of CKD patients. Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD.

Add-back therapy use and its impact on LA persistence in patients with endometriosis.

OBJECTIVES: Persistence and compliance in women with endometriosis who are receiving gonadotropin-releasing hormone agonists (GnRH-a) may be limited by its hypoestrogenic side effects. Use of concomitant therapy with norethindrone acetate (NA), estrogen, estrogen/progestin combinations, or other progestin (i.e., 'add-back therapy' [ABT]) is recommended to alleviate these side effects. This retrospective study evaluated ABT utilization and its effect on compliance and persistence in patients with endometriosis taking the GnRH-a leuprolide acetate (LA) depot suspension. METHODS: A retrospective analysis of a large pharmacy claims database identified patients who started LA therapy from 2002 to 2004 for the treatment of endometriosis. Patients were identified as having received ABT if they started 7 days before, or within 45 days of the last LA fill. RESULTS: A total of 1285 women with endometriosis who began using LA were identified with 12 months of evaluable data: 211 (16.4%) used concomitant NA therapy, 116 (9.0%) used concomitant estrogen-based therapy, 28 (2.2%) used concomitant combination estrogen- and progestin-based therapies, 56 (4.4%) used concomitant progestin-based therapy, and 874 (68.0%) did not use any ABT. Mean (+/-SD) LA persistence in women receiving NA-based ABT was 5.83 +/- 2.98 months, compared with 4.25 +/- 2.62 months for those not using ABT (P < 0.0001). Average medication possession ratio was 0.43 +/- 0.20 for women receiving NA-based ABT versus 0.32 +/- 0.18 for those not receiving any ABT (P < 0.0001). Patients < 30 years of age were most likely to continue therapy longer and have greater compliance compared with the older age group cohorts (P < 0.01). Patients who used ABT continued to do so for 3.79 +/- 3.21 months. LIMITATIONS: Limitations of this study include those associated with the use of retrospective claims databases: It does not include any information regarding the patient's pain symptoms, disease severity, or other factors, which could correlate to compliance and persistence. CONCLUSIONS: Among women using LA therapy for endometriosis, only 32% used any type of ABT, and these patients had significantly higher persistence and compliance with LA therapy compared to no ABT user group.

GERD-related health care utilization, therapy, and reasons for transfer of GERD patients between primary care providers and gastroenterologists in a US managed care setting.

PURPOSE: Patient flow between primary care physicians and gastroenterologists in the continuum of gastroesophageal reflux disease (GERD) care is poorly understood. Using administrative claims data from a large US health plan linked with data abstracted from medical records, we examined: health care resource utilization for GERD subjects treated by primary care physicians (PCPs) and gastroenterologists (GEs), determinants of GERD subject transfer between these physician types, and reasons for GERD therapy change. RESULTS: Within a sample of 169,884 patients, 211,043 PCP-based episodes of care and 40,304 GE-based episodes of care were developed. In unadjusted comparisons, GE episodes were characterized by more endoscopic procedures, on average (50.5/100 episodes), compared with PCP episodes (6.3/100, P < 0.001). Multivariate analysis showed that patients with esophagitis had 57.3% higher odds (P < 0.01) of transfer from PCP to GE compared with patients without esophagitis; patients with esophageal stricture had 98.6% higher odds (P < 0.01) of PCP-GE transfer. Patients with endoscopy during a first GE episode had 32.2% higher odds of transfer to a PCP (P < 0.01). The principal reasons for change in GERD therapy were no change or worsening of symptoms (51.7% of PCP charts; 9.5% of GE charts) and lack of response to therapy (51.7% of PCP charts, 26.2% of GE charts). CONCLUSION: Resource utilization varies greatly based on the physician's specialty. We infer that timely transfer of GERD patients to gastroenterologists when empiric treatment is insufficient may lead to more efficient clinical management.