Effect of a Home-Based Wearable Continuous ECG Monitoring Patch on Detection of Undiagnosed Atrial Fibrillation: The mSToPS Randomized Clinical Trial.

Importance: Opportunistic screening for atrial fibrillation (AF) is recommended, and improved methods of early identification could allow for the initiation of appropriate therapies to prevent the adverse health outcomes associated with AF. Objective: To determine the effect of a self-applied wearable electrocardiogram (ECG) patch in detecting AF and the clinical consequences associated with such a detection strategy. Design, Setting, and Participants: A direct-to-participant randomized clinical trial and prospective matched observational cohort study were conducted among members of a large national health plan. Recruitment began November 17, 2015, and was completed on October 4, 2016, and 1-year claims-based follow-up concluded in January 2018. For the clinical trial, 2659 individuals were randomized to active home-based monitoring to start immediately or delayed by 4 months. For the observational study, 2 deidentified age-, sex- and CHA2DS2-VASc-matched controls were selected for each actively monitored individual. Interventions: The actively monitored cohort wore a self-applied continuous ECG monitoring patch at home during routine activities for up to 4 weeks, initiated either immediately after enrolling (n = 1364) or delayed for 4 months after enrollment (n = 1291). Main Outcomes and Measures: The primary end point was the incidence of a new diagnosis of AF at 4 months among those randomized to immediate monitoring vs delayed monitoring. A secondary end point was new AF diagnosis at 1 year in the combined actively monitored groups vs matched observational controls. Other outcomes included new prescriptions for anticoagulants and health care utilization (outpatient cardiology visits, primary care visits, or AF-related emergency department visits and hospitalizations) at 1 year. Results: The randomized groups included 2659 participants (mean [SD] age, 72.4 [7.3] years; 38.6% women), of whom 1738 (65.4%) completed active monitoring. The observational study comprised 5214 (mean [SD] age, 73.7 [7.0] years; 40.5% women; median CHA2DS2-VASc score, 3.0), including 1738 actively monitored individuals from the randomized trial and 3476 matched controls. In the randomized study, new AF was identified by 4 months in 3.9% (53/1366) of the immediate group vs 0.9% (12/1293) in the delayed group (absolute difference, 3.0% [95% CI, 1.8%-4.1%]). At 1 year, AF was newly diagnosed in 109 monitored (6.7 per 100 person-years) and 81 unmonitored (2.6 per 100 person-years; difference, 4.1 [95% CI, 3.9-4.2]) individuals. Active monitoring was associated with increased initiation of anticoagulants (5.7 vs 3.7 per 100 person-years; difference, 2.0 [95% CI, 1.9-2.2]), outpatient cardiology visits (33.5 vs 26.0 per 100 person-years; difference, 7.5 [95% CI, 7.2-7.9), and primary care visits (83.5 vs 82.6 per 100 person-years; difference, 0.9 [95% CI, 0.4-1.5]). There was no difference in AF-related emergency department visits and hospitalizations (1.3 vs 1.4 per 100 person-years; difference, 0.1 [95% CI, -0.1 to 0]). Conclusions and Relevance: Among individuals at high risk for AF, immediate monitoring with a home-based wearable ECG sensor patch, compared with delayed monitoring, resulted in a higher rate of AF diagnosis after 4 months. Monitored individuals, compared with nonmonitored controls, had higher rates of AF diagnosis, greater initiation of anticoagulants, but also increased health care resource utilization at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT02506244.

Patient Preference for Dosing Frequency Based on Prior Biologic Experience.

BACKGROUND: There is limited research exploring patient preferences regarding dosing frequency of biologic treatment of psoriasis. METHODS: Patients with moderate-to-severe plaque psoriasis identified in a healthcare claims database completed a survey regarding experience with psoriasis treatments and preferred dosing frequency. Survey questions regarding preferences were posed in two ways: (1) by likelihood of choosing once per week or 2 weeks, or 12 weeks; and (2) by choosing one option among once every 1-2 or 3-4 weeks or 1-2 or 2-3 months. Data were analyzed by prior biologic history (biologic-experienced vs biologic-naïve, and with one or two specific biologics). RESULTS: Overall, 426 patients completed the survey: 163 biologic-naïve patients and 263 biologic-experienced patients (159 had some experience with etanercept, 105 with adalimumab, and 49 with ustekinumab). Among patients who indicated experience with one or two biologics, data were available for 219 (30 with three biologics and 14 did not specify which biologic experience). The majority of biologic-naïve (68.8%) and overall biologic-experienced (69.4%) patients indicated that they were very likely to choose the least frequent dosing option of once every 12 weeks (Table 1). In contrast, fewer biologic-naïve (9.1% and 16.7%) and biologic-experienced (22.5% and 25.3%) patients indicated that they were very likely to choose the 1-week and 2-week dosing interval options, respectively. In each cohort grouped by experience with specific biologics, among those with no experience with ustekinumab, the most chosen option was 1-2 weeks. The most frequently chosen option was every 2-3 months, among patients with any experience with ustekinumab, regardless of their experience with other biologics. CONCLUSIONS: The least frequent dosing interval was preferred among biologic naïve patients and patients who had any experience with ustekinumab. Dosing interval may influence the shared decision-making process for psoriasis treatment with biologics.

J Drugs Dermatol. 2017;16(3):220-226.

Rationale and design of a home-based trial using wearable sensors to detect asymptomatic atrial fibrillation in a targeted population: The mHealth Screening To Prevent Strokes (mSToPS) trial.

Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed-monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF.

Treatment patterns and perceptions of treatment attributes, satisfaction and effectiveness among patients with psoriasis.

Psoriasis is a chronic autoimmune condition that affects over 7 million Americans, approximately 1-3 percent of the population. Although there are a number of treatment options currently available, little is known about the treatment patterns of patients. Using data from 1,006 psoriasis sufferers, the aim of the present study was to analyze patients' treatment timeline, as well as their perceptions about these treatments. Most respondents were white, female and had health insurance. The results suggested that over-the-counter (OTC) and prescription topicals were the most common initial treatments, but systemic orals and biologics were the most common treatments for patients who required a third-line or fourth-line treatment (and for patients with greater severity). Treatment dissatisfaction was relatively high, with very few positive attributes associated with the current treatment options. Overall, this study suggests that treatment options vary (at a statistically significant level) as a function of severity, and many patients, despite the choices in the number and quality of treatment options, are generally dissatisfied.

Healthcare resource utilization following ECG sensor patch screening for atrial fibrillation.

BACKGROUND: Screening for asymptomatic, undiagnosed atrial fibrillation (AF) has the potential to allow earlier treatment, possibly resulting in prevention of strokes, but also to increase medical resource utilization. OBJECTIVE: To compare healthcare utilization rates during the year following initiation of screening among participants screened for AF by electrocardiogram (ECG) sensor patch compared with a matched observational control group. METHODS: A total of 1718 participants recruited from a health care plan based on age and comorbidities who were screened with an ECG patch (actively monitored group) as part of a prospective, pragmatic research trial were matched by age, sex, and CHA2DS2-VASc score with 3371 members from the same health plan (observational control group). Healthcare utilization, including visits, prescriptions, procedures, and diagnoses, during the 1 year following screening was compared between the groups using health plan claims data. RESULTS: Overall, the actively monitored group had significantly higher rates of cardiology visits (adjusted incidence rate ratio [aIRR] [95% confidence interval (CI)]: 1.43 [1.27, 1.60]), no difference in primary care provider visits (aIRR [95% CI]: 1.0 [0.95, 1.05]), but lower rates of emergency department (ED) visits and hospitalizations (aIRR [95% CI]: 0.80 [0.69, 0.92]) compared with controls. Among those with newly diagnosed AF, the reduction in ED visits and hospitalizations was even greater (aIRR [95% CI]: 0.27 [0.17, 0.43]). CONCLUSION: AF screening in an asymptomatic, moderate-risk population with an ECG patch was associated with an increase in cardiology outpatient visits but also significantly lower rates of ED visits and hospitalizations over the 1 year following screening.

Digital recruitment and enrollment in a remote nationwide trial of screening for undiagnosed atrial fibrillation: Lessons from the randomized, controlled mSToPS trial.

OBJECTIVES: The advent of large databases, wearable technology, and novel communications methods has the potential to expand the pool of candidate research participants and offer them the flexibility and convenience of participating in remote research. However, reports of their effectiveness are sparse. We assessed the use of various forms of outreach within a nationwide randomized clinical trial being conducted entirely by remote means. METHODS: Candidate participants at possibly higher risk for atrial fibrillation were identified by means of a large insurance claims database and invited to participate in the study by their insurance provider. Enrolled participants were randomly assigned to one of two groups testing a wearable sensor device for detection of the arrhythmia. RESULTS: Over 10 months, the various outreach methods used resulted in enrollment of 2659 participants meeting eligibility criteria. Starting with a baseline enrollment rate of 0.8% in response to an email invitation, the recruitment campaign was iteratively optimized to ultimately include website changes and the use of a five-step outreach process (three short, personalized emails and two direct mailers) that highlighted the appeal of new technology used in the study, resulting in an enrollment rate of 9.4%. Messaging that highlighted access to new technology outperformed both appeals to altruism and appeals that highlighted accessing personal health information. CONCLUSIONS: Targeted outreach, enrollment, and management of large remote clinical trials is feasible and can be improved with an iterative approach, although more work is needed to learn how to best recruit and retain potential research participants. TRIAL REGISTRATION: Clinicaltrials.govNCT02506244. Registered 23 July 2015.

Red blood cell transfusions and the risk of acute respiratory distress syndrome among the critically ill: a cohort study.

INTRODUCTION: Recent data indicate that transfusion of packed red blood cells (pRBCs) may increase the risk for the development of acute respiratory distress syndrome (ARDS) in critically ill patients. Uncertainty remains regarding the strength of this relationship. METHODS: To quantify the association between transfusions and intensive care unit (ICU)-onset ARDS, we performed a cohort study within Crit, a multicenter, prospective, observational study of transfusion practice in the ICU which enrolled 4,892 critically ill patients in 284 ICUs in the United States. Diagnostic criteria for ARDS were prospectively defined, and we focused on subjects without ARDS at admission. The development of ARDS in the ICU served as the primary endpoint. RESULTS: Among the 4,730 patients without ARDS at admission, 246 (5.2%) developed ARDS in the ICU. At baseline, ARDS cases were younger, more likely to be in a surgical ICU, and more likely to be admitted with pneumonia or sepsis than controls without ARDS. Cases also were more likely to have a serum creatinine of greater than 2.0 mg/dl (23% versus 18%) and a serum albumin of less than or equal to 2.3 g/dl (54% versus 30%) and were more severely ill upon ICU admission as measured by either the APACHE II (Acute Physiology and Chronic Health Evaluation II) or SOFA (Sequential Organ Failure Assessment) score (p < 0.05 for all). Sixty-seven percent and 42% of cases and controls, respectively, had exposure to pRBC transfusions (p < 0.05), and the unadjusted odds ratio (OR) of developing ARDS in transfused patients was 2.74 (95% confidence interval [CI], 2.09 to 3.59; p < 0.0001) compared to those never transfused. After age, baseline severity of illness, admitting diagnosis, and process-of-care factors were adjusted for, the independent relationship between pRBC transfusions and ICU-onset ARDS remained significant (adjusted OR, 2.80; 95% CI, 1.90 to 4.12; p < 0.0001). CONCLUSION: Development of ARDS after ICU admission is common, occurring in approximately 5% of critically ill patients. Transfusion of pRBCs is independently associated with the development of ARDS in the ICU.

Burden of illness among commercially insured patients with Alzheimer's disease.

BACKGROUND: The purpose of this study was to examine the direct costs of care for patients newly diagnosed with Alzheimer's disease (AD) by using retrospective healthcare claims data. METHODS: Patients aged 65 years or older with >or=1 claims containing a listed diagnosis of AD between January 1999 and November 2003 were selected. The first observed AD claim was deemed the index date. Control patients with no evidence of AD or dementia also were identified. Patients had a 12-month pre-index period and minimum 30-day follow-up. AD patients were matched to control patients on the basis of age, gender, and follow-up duration. Annualized utilization and costs were calculated; generalized linear models (GLM) were undertaken, controlling for demographic and clinical characteristics. Analyses focused on differences in costs among AD patients and controls. RESULTS: The average age of AD and control patients was 82 years; 38% were men (n = 2,475 AD; 4,950 controls). Average total costs for AD patients were more than five-fold higher compared with controls ($28,263 vs $5,880; P < .001), driven primarily by inpatient costs. Total costs were significantly higher (P < .001) for AD patients in GLM modeling, with diagnosis group (AD vs control) as the most important predictor. Adjusted annual costs per patient were also five-fold higher ($21,150 vs $4,053 for AD vs control, respectively) during the follow-up period. CONCLUSIONS: The annual economic burden of AD to third-party payers is more substantial than previously estimated ($3,805 to $8,200).

The economic effect of oral linezolid versus intravenous vancomycin in the outpatient setting: the payer perspective.

Oral antibiotic therapy can reduce complications and costs compared with intravenous (IV) therapy. The object of this study was to determine the health economic and resource utilization effects of outpatient treatment with oral linezolid relative to IV vancomycin. Longitudinal claims data from 80 health care plans were used. Patients 18 years and older, who did not have osteomyelitis, with a pharmacy claim for linezolid or vancomycin between January 1, 2002 and March 31, 2004 were eligible. Clinical and resource utilization data were collected for 12 months before and 35 days after treatment. Patients treated with linezolid were matched with controls treated with vancomycin, based on propensity scoring. Direct medical costs paid by health plans were compared. A total of 1,048 matched pairs were identified. Demographic and clinical characteristics were comparable between groups. Patients with linezolid claims had lower resource utilization versus those with vancomycin claims during follow-up, including fewer mean physician office visits (4.1+/-5.7 vs. 8.4+/-13.8 visits; P< .001); lab/diagnostic claims (6.3+/-18.0 vs. 10.4 +/-15.2 claims; P< .001); pharmacy claims (7.3+/-8.1 vs. 13.6+/-17.4 claims; P< .001); emergency room visits (9.7% vs. 13.9%; P= .003) and hospitalization (15.3% vs. 19.1%; P= .024). Patients receiving vancomycin were more likely to be hospitalized or have an emergency room visit than patients receiving linezolid. Mean total adjusted cost was 4,707 dollars less for linezolid compared with vancomycin (8,401dollars vs. 13,108 dollars; P< .001). Similar trends were observed for patients matched based on complicated skin and soft tissue infection diagnosis. Outpatient treatment with oral linezolid was associated with significantly lower resource utilization and total medical costs compared with IV vancomycin.

Effect of initial ziprasidone dose on length of therapy in schizophrenia.

OBJECTIVE: To examine the effects of initial ziprasidone dose on discontinuation rates, using retrospective integrated medical and pharmacy claims data. METHODS: Patients > or = 18 years with a diagnosis of schizophrenia or schizoaffective disorder and a ziprasidone claim between March 2001 and February 2003 who were continuously enrolled for at least six months before and three months after initiation of ziprasidone were included. They were stratified by initial daily dose (> or = 40 and < 80 mg [low] vs. > or = 80 and < 120 mg [medium] vs. 120-160 mg [high]). The six-month risk of discontinuation was examined using Cox proportional hazards models controlling for gender, psychiatric comorbidities, and pre-ziprasidone utilization of antipsychotics (atypical, conventional, none). RESULTS: The mean age of the sample (n=1058) was 38 years; 42% were male. The six-month risk of discontinuation was significantly lower in patients in the high-dose group as compared to the low-dose group (HR=0.737 for high-dose vs. low-dose, 95% CI=0.581, 0.935; P=0.012) and trended towards significance when comparing high-dose and medium-dose groups (HR=0.857 for high-dose vs. medium-dose, 95% CI=0.694, 1.059; P=0.153). CONCLUSIONS: Patients initiating ziprasidone therapy with an initial dose of at least 120 mg/day had better medication adherence compared to those initiating at lower doses. These findings confirm results seen in clinical trials suggesting improved efficacy and tolerability at higher ziprasidone doses.

Patient reported health outcomes and non-adherence in psoriasis patients receiving adalimumab or ustekinumab for moderate to severe plaque psoriasis.

OBJECTIVE: The objective of this study is to compare health outcomes of patients using biologic therapies ustekinumab (UST) or adalimumab (ADA) for moderate-to-severe plaque psoriasis (PsO) and assess biologics non-adherence. METHODS: Two phases of web-based survey data were collected, assessing adult patients with PsO from a Diplomat® Specialty Pharmacy US claims database (Diplomat Specialty Pharmacy; Flint, MI). Measures included demographics, treatment and health characteristics/behaviors, treatment satisfaction, health-related quality of life (HRQoL), and productivity. Pooled and stratified (by biologics experience) bivariate and multivariable analyses were conducted. RESULTS: UST (n = 262) versus ADA (n = 83) users more frequently had psoriasis cleared (40.5% versus 15.4%, respectively, with no visible signs), better HRQoL as per Dermatology Life Quality Index (DLQI) score = 0 (45.2% versus 19.2%), and higher current effectiveness satisfaction, all p < 0.05. Adjusting for covariates, UST versus ADA bio-naïve patients (n = 68) had better (53.4% lower) DLQI scores, lower percent body surface affected (%BSA; 0.85 versus 1.43), more %BSA improvement (-1.60 versus -1.03), and lower activity impairment (90.4% lower), all p < 0.05. Non-adherence to UST (11.8%) versus ADA (32.5%) was lower, p < 0.05, and more access versus forgetfulness-related. However, no significant differences emerged on outcomes between overall or bio-experienced UST and ADA users. CONCLUSIONS: UST versus ADA PsO bio-naïve patients reported higher clearing rates, better DLQI, and lower activity impairment.

A multicenter, non-interventional study to evaluate patient-reported experiences of living with psoriasis.

BACKGROUND: Moderate to severe plaque psoriasis (with or without psoriatic arthritis) places significant burden on patients' lives. OBJECTIVE: Explore and document patients' experiences of living with psoriasis, including symptoms, treatments, impact on daily lives and patient-reported functioning. METHODS: In a US-based, non-interventional study, narrative interviews were conducted at baseline and again within 16 weeks. In interviews, patients with moderate to severe psoriasis indicated symptoms, ranked symptoms according to level of bother and indicated areas of their lives affected by psoriasis. Transcripts of interviews were coded for themes. Measurements of psoriasis severity including BSA, PGA and PASI were recorded. RESULTS: Symptoms reported most frequently included flaking/scaling (non-scalp areas), itching/scratching and rash, while the most bothersome symptoms were itching/scratching, flaking/scaling (non-scalp areas) and skin pain. Frequently reported impact areas were social and emotional. CONCLUSION: Broad-reaching interviews with patients with psoriasis show that these patients suffer in many aspects of their lives and in ways not indicated by typical psoriasis severity measures. Patients with psoriatic arthritis reported symptoms and disease-related complications at higher rates than those without arthritis. Physicians' explorations of the effect of psoriasis on patients' life events could aid in managing these patients.

Ustekinumab dosing, persistence, and discontinuation patterns in patients with moderate-to-severe psoriasis.

OBJECTIVES: Ustekinumab is the most recently approved biologic for the treatment of moderate-to-severe psoriasis. Real-world dosing patterns of ustekinumab are yet to be fully characterized. METHODS: A retrospective, observational study was conducted using MarketScan Commercial and Medicare databases. A cohort of psoriasis patients treated with ustekinumab between 25 September 2009 and 31 October 2010 was evaluated. Main outcomes included ustekinumab dosing and treatment patterns. Kaplan-Meier estimates were calculated to adjust for the censoring of data. Subgroup analysis was conducted for biologic-experienced patients and biologic-naïve patients. RESULTS: One thousand ustekinumab patients were included, of whom 60% were biologic-experienced. The average age was 49.0 and 53.9% were male. 63.3% of patients initiated ustekinumab with a 45 mg dose and 34.5% initiated with a 90 mg dose. Mean (median) days from initial dose to second dose was 31.1 (28.0). During maintenance therapy, dose intervals spanned from 80.6 to 81.2 (84.0) days. About 81.4% of patients were persistent during the variable-length follow-up period. CONCLUSIONS: The majority of patients received the 45 mg ustekinumab dose. The mean dosing intervals were consistent with the US prescribing guidelines. Biologic-naïve and biologic-experienced patients had similar dosing patterns. Ustekinumab treatment achieved a persistency rate as high as 81.4% over an average of 186.5 (SD 114.2) days of follow-up.

Patient-reported treatment satisfaction and choice of dosing frequency with biologic treatment for moderate to severe plaque psoriasis.

BACKGROUND: Moderate to severe plaque psoriasis has a serious effect on health-related quality of life. Patients treated with biologic medications place importance on satisfaction and treatment frequency options. We assessed patient-reported treatment satisfaction and dosing frequency choice with biologics. METHODS: We used a health care claims database to identify patients with moderate to severe plaque psoriasis. Participants completed the Treatment Satisfaction Questionnaire for Medication. Results were compared between patients experienced with biologics (adalimumab, etanercept, or ustekinumab) or not (cyclosporine or methotrexate). Participants were asked for their choices of dosing options of once every 1-2 weeks, 3-4 weeks, 1-2 months, or 2-3 months. Participants were also asked for their choices of dosing options of every 1, 2, 3, and so on up to every 12+ weeks. RESULTS: A total of 426 patients completed the survey (263 biologic-experienced and 163 biologic-naïve patients). Patient satisfaction with psoriasis treatment was significantly higher in the biologic-experienced cohort. The most frequently chosen option (38.8% of all participating patients) was every 2-3 months; 37.3% chose once every 1-2 weeks. Significant differences were found in the percentage of biologic-naïve patients choosing 2-3-month (49.7%) over 1-2-week (20.9%) dosing (P<0.001). Among biologic-experienced patients, the difference between the percentage of patients choosing the 2-3-month (35.7%) and 1-2-week (41.8%) options was not significant (P=0.264). The two most often week-specific intervals chosen by biologic-naïve patients were 12+ weeks (42.3%) and 4 weeks (15.6%). The biologic-experienced patients most often chose 12+ weeks (31.2%) and 1 week (25.9%). CONCLUSION: Patients using biologics reported satisfaction with their treatment, which may positively affect outcomes. Longer dosing intervals were chosen most frequently among all patients combined. Reports of patient satisfaction with prior treatments and choices regarding dosing frequency, among all other considerations, should be evaluated in determining an appropriate biologic medication for psoriasis.

Risk of constipation in patients prescribed fentanyl transdermal system or oxycodone hydrochloride controlled-release in a California Medicaid population.

OBJECTIVE: To compare the risk of developing constipation between patients prescribed fentanyl transdermal system or oxycodone hydrochloride (HCl) controlled-release. DESIGN: California Medicaid (Medi-Cal) claims data. SETTING: Medicaid beneficiaries in California. PARTICIPANTS: Chronic pain patients who received a prescription for transdermal fentanyl or oxycodone controlled-release between October 1, 1997, and February 28, 2000, for at least three consecutive months. MAIN OUTCOME MEASURES: Constipation was defined using the International Classification of Diseases, Ninth Revision, Clinical Modification code (ICD-9-CM 564.0). The association between long-acting opioid use and constipation was determined by multivariate logistic regression after controlling for drug strength, short-acting opioid usage, and comorbidities. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were reported. RESULTS: A total of 2,095 patients were included in the regression analysis (transdermal fentanyl = 877; oxycodone controlled-release = 1,218). Seventy-five patients received a constipation diagnosis (transdermal fentanyl = 28; oxycodone controlled-release = 47). Approximately 40% of patients were at least 65 years of age. Overall, oxycodone controlled-release patients had a significantly greater risk of developing constipation compared with transdermal fentanyl patients (transdermal fentanyl: n = 877; oxycodone controlled-release: n=1,218; OR = 2.55; 95% CI = 1.33-4.89; P = 0.005). Among patients who were 65 years or older, oxycodone controlled-release patients were 7.33 times more likely to be constipated than transdermal fentanyl patients (transdermal fentanyl: n = 518; oxycodone controlled-release: n = 317; OR = 7.33; 95% CI = 1.98-27.13; P = 0.003). CONCLUSION: These findings suggest that patients prescribed transdermal fentanyl may have a significantly lower risk of developing constipation compared with oxycodone controlled-release, particularly in the elderly.

Adalimumab, etanercept, and infliximab utilization patterns and drug costs among rheumatoid arthritis patients.

OBJECTIVES: To evaluate the utilization patterns of the anti-tumor necrosis factor (anti-TNF) agents Humira (adalimumab), Enbrel (etanercept), and Remicade (infliximab) in patients with rheumatoid arthritis (RA) and compare medication costs during the first year of treatment. (Humira is a registered trademark of Abbott Laboratories, IL; Enbrel is a registered trademark of Immunex Corporation, CA; and Remicade is a registered trademark of Janssen Biotech, Inc., PA). METHODS: This retrospective analysis of medical and pharmacy claims included patients who were aged ≥18 years, had ≥2 RA diagnosis codes, and had ≥365 days of persistence with the index anti-TNF. Patients excluded had claims for anti-TNF agents within 6 months before the index date. Refill patterns for adalimumab and etanercept, number of infliximab infusions, time between infusions, and dose per infusion were analyzed for 12 months. Direct anti-TNF medication costs were compared among anti-TNFs for the initial treatment year. RESULTS: Infliximab-treated patients (n = 457) were significantly older than adalimumab- (n = 337) or etanercept-treated patients (n = 902). Time between refills was longer than recommended for 28% and 30% of adalimumab and etanercept refill periods, respectively. Potential cumulative time without therapy was 33 days for adalimumab and 43 days for etanercept. Statistically significant differences in mean per-patient anti-TNF medication costs for the first year were reported for adalimumab, etanercept, and infliximab ($14,991, $13,361, and $18,139, respectively; p < 0.0001); however, a cost assessment using labeled dosing of the anti-TNF agents with optimal treatment compliance yielded comparable annual medication costs. LIMITATIONS: This analysis only evaluated utilization patterns for selected anti-TNF agents and was not inclusive of other medications that patients may have been using for RA. Absolute patient adherence could not be assessed due to lack of information on how patients were self-administering adalimumab and etanercept or if samples of the agents were made available. CONCLUSIONS: This study identified gaps in patients' refills compared with prescriber recommendations. The infliximab-treated group had infusion patterns consistent with prescribing information. Potential clinical and economic implications of dose attenuation with adalimumab and etanercept should be explored further.

Effect of a continuous measure of adherence with infliximab maintenance treatment on inpatient outcomes in Crohn's disease.

BACKGROUND: To assess the impact of a continuous measure of adherence with infliximab maintenance treatment in Crohn's disease (CD) during the first year of treatment on CD-related health care utilization, CD-related hospitalizations, inpatient costs, and length of hospital stay. PATIENTS AND METHODS: A retrospective claims analysis using the IMS LifeLink Health Plan Claims Database (September 1, 2004, to June 30, 2009) was conducted. Continuous enrollment for 12 months before and 12 months after the index date was required. Patients were required to have at least two claims with an International Classification of Diseases, 9th Revision, Clinical Modification diagnosis code for CD (555.xx) pre-index and be aged ≥ 18 years at index. Patients with three infusions during the first 56 days post-index and at least one infusion following day 56 post-index were considered to have maintenance therapy. Adherence and nonadherence were defined as a medication possession ratio of ≥ 80% and < 80%, respectively. RESULTS: Four hundred forty-eight patients were included in the analysis (mean age, 42.6 years; 56% female; mean ± standard deviation [SD] and median number of infliximab infusions, 7.35 ± 1.60 and 8). The number of patients who met the definition of adherence was 344 (77%). CD-related health care utilization was not significantly impacted by adherence except for ancillary services and radiology. Fewer adherent patients were hospitalized compared with nonadherent patients (9% versus 16%; P = 0.03). Adherent patients had fewer mean ± SD and median days in the hospital (5.5 ± 3.4 and 5 days) compared with nonadherent patients (13.1 ± 14.2 and 8 days; P = 0.01). Mean ± SD and median hospital costs were significantly greater for nonadherent patients ($40,822 ± $49,238 and $28,864) compared with adherent patients ($13,704 ± $10,816 and $9938; P = 0.002). CONCLUSION: Adherence with maintenance infliximab over 12 months was associated with lower rates of CD-related hospitalizations and inpatient costs and a shorter length of hospital stay.

Comparative multidatabase analysis of dosing patterns and infusion intervals for the first 12 infliximab infusions in patients with rheumatoid arthritis.

BACKGROUND: According to prescribing information for rheumatoid arthritis (RA) treatments in the United States, infliximab should be administered at weeks 1, 2, 6, and then every 8 weeks starting at a 3-mg/kg dose, with flexible dosing up to 10 mg/kg and/or every 4 weeks based on clinical response. OBJECTIVE: This study evaluated dosing and intervals of the first 12 infliximab infusions in patients with RA across multiple large administrative databases. METHODS: Data were obtained from 4 databases: HealthCore Integrated Research Database (HIRD), IMS LifeLink Health Plan Claims Database (IMS Lifelink), Premier Perspective Database (PPD), and Wolters Kluwer Pharma Solutions (WKPS). Patients were aged ≥18 years, diagnosed with RA, and naive to biologic therapy. Patients with other select inflammatory conditions were excluded. The induction period included infusions 1 through 3; the maintenance period included infusions 4 through 12. RESULTS: Observed dosing patterns from the HIRD, IMS LifeLink, PPD, and WKPS databases demonstrated minimal dose increases from the first infusion (93.5, 103.3, 58.8, and 73.2 mg, respectively) and from the first maintenance infusion (69.1, 64.3, 45.7, and 45.7 mg, respectively) to the highest dose during the first 12 infusions. The mean number of days between infusions in the maintenance period ranged from 53.3 to 63.5 in HIRD, 53.7 to 60.3 in IMS LifeLink, 53.4 to 59.4 in PPD, and 52.3 to 55.0 in the WKPS database. CONCLUSION: Data from multiple databases of patients with RA suggest that, in clinical practice, infliximab dosing and intervals are consistent with FDA prescribing information and remain relatively stable during the first 12 infusions.

Impact of infliximab adherence on Crohn's disease-related healthcare utilization and inpatient costs.

INTRODUCTION: Few published reports have described the impact of adherence with biologic agents on hospitalizations and inpatient costs in Crohn's disease (CD). METHODS: A retrospective claims analysis using the IMS LifeLink Health Plan Claims Database between September 1, 2004 and June 30, 2009 was conducted. Continuous enrollment for 12 months before and 12 months after the index date was required. Patients were required to have ≥2 claims with an International Classification of Diseases, 9th Edition, Clinical Modification diagnosis code for CD (555.xx) preindex, be ≥18 years of age at index, and have ≥4 infliximab infusions with a gap no greater than 12 weeks between each infusion. Patients with 7-9 infliximab infusions (12 months postindex) were considered adherent; patients with 4-6 infliximab infusions were considered nonadherent. RESULTS: In total, 638 patients were included in the analyses (mean age, 43 years; 58% female in the adherent group and 53% in the nonadherent group). The number of patients who met the definition of adherence was 466 (73%). A smaller proportion of adherent patients had a CD-related emergency room visit, compared with nonadherent patients (11% vs. 17%, P=0.029). A smaller proportion of adherent patients required CD-related hospitalization, compared with nonadherent patients (8% vs. 12%, P=0.117). Among those hospitalized, adherent patients had fewer mean [median] days in the hospital (5.9 [5] days), compared with nonadherent patients (12.8 [8] days, P=0.015). Mean [median] hospital costs were significantly lower for adherent patients ($13,427 [$9,352]), compared with nonadherent patients ($37,783 [$28,864], P=0.001). Multivariate analyses confirmed lower inpatient (P<0.001) costs for adherent versus nonadherent patients. CONCLUSION: Adherence with infliximab therapy during the first year of treatment in patients with CD was associated with a shorter hospital length of stay and lower inpatient costs compared with nonadherent patients. Strategies for increasing adherence rates to infliximab maintenance therapy may be valuable in reducing hospitalizations and inpatient costs in patients with CD.

Impact of persistence with infliximab on hospitalizations in ulcerative colitis.

OBJECTIVES: To assess infliximab infusion patterns in ulcerative colitis (UC) and assess the impact of persistence with infliximab maintenance therapy on UC-related hospitalizations, lengths of stay, and inpatient costs. STUDY DESIGN: Retrospective analysis of medical claims for UC patients newly initiating infliximab treatment. METHODS: Patients were aged >18 years and had 2 UC diagnosis codes, an infliximab index date between September 1, 2005, and January 31, 2008, and continuous enrollment for >12 months before and >14 months after the index date. Infliximab induction (first 56 days postindex) and maintenance (>56 days and <12 months postinduction) patterns were evaluated. Of patients with maintenance treatment, persistence was defined as a medication possession ratio (MPR) of >80%, and this group was compared with those without persistence (<80% MPR). RESULTS: Overall, 420 patients were included in the analysis; 84.3% (n = 354) continued to maintenance therapy. Maintenance infusion patterns were consistent with recommended prescribing information. A smaller proportion of patients with maintenance therapy persistence required hospitalization compared with patients without persistence (3.0% vs 20.4%; P <.001). Hospitalized patients with maintenance therapy persistence had significantly lower mean inpatient costs ($14,243 vs $32,745; P = .046), with a trend toward shorter mean lengths of stay (6.67 vs 9.71 days; P = .147) than patients without persistence. CONCLUSIONS: Infliximab maintenance therapy persistence in UC was associated with significantly fewer hospitalizations. Once hospitalized, patients with therapeutic persistence had significantly decreased inpatient costs.