Evaluating the Efficacy of Crisaborole Using the Atopic Dermatitis Severity Index and Percentage of Affected Body Surface Area.

Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis pools results from 2 phase 3 studies (ClinicalTrials.gov, NCT02118766 [AD-301]; NCT02118792 [AD-302]) to evaluate crisaborole efficacy in patients ≥ 2 years with mild-to-moderate atopic dermatitis (per Investigator's Static Global Assessment) using the Atopic Dermatitis Severity Index (ADSI) and percentage of treatable body surface area (%BSA). Patients were randomly assigned 2:1 to receive crisaborole (n = 1,016) or vehicle (n = 506) twice daily for 28 days. ADSI scores were the sum of pruritus, erythema, exudation, excoriation, and lichenification severity scores, each graded on a 4-point scale from none (0) to severe (3). Respective mean changes in ADSI score and %BSA at day 29 were (crisaborole vs. vehicle) -3.52 versus -2.42 (p < 0.0001) and -7.43 versus -4.44 (p < 0.0001). Crisaborole was effective in treating mild-to-moderate atopic dermatitis based on ADSI and %BSA.

Direct and Indirect Effects of Crisaborole Ointment on Quality of Life in Patients with Atopic Dermatitis: A Mediation Analysis.

Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis. Using pooled data from two phase 3 studies (NCT02118766/NCT02118792), mediation modeling determined the interrelationship among pruritus, quality of life (QoL), and treatment. Patients aged ≥ 2 years received crisaborole ointment 2% or vehicle twice daily for 28 days. QoL measures were Dermatology Life Quality Index (DLQI) (≥ 16 years) and Children's Dermatology Life Quality Index (CDLQI) (2-15 years). Pruritus was assessed by the Severity of Pruritus Scale (4-point scale from 0 to 3). The indirect effect of crisaborole on QoL mediated through its effect on pruritus was 51% (DLQI model, p < 0.05) and 72% (CDLQI model, p < 0.05). Direct effect (other effects) on QoL was 49% (DLQI model, p < 0.05) and 28% (CDLQI model, p > 0.05). Mediation modeling shows that crisaborole affects QoL mostly indirectly through pruritus severity reduction.

Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment.

BACKGROUND AND PURPOSE: An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren's contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC's impact on quality of life and the value of its treatments. METHODS: Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were defined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little fingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0-1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L profile most accurately reflects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. RESULTS: Estimated utilities based on the responses of 1,745 qualified respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little fingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little finger from 50 to 12 degrees would improve utility by 0.02. INTERPRETATION: DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and flexible framework to assess utility for varying degrees of DC severity.

Dupuytren's contracture: a retrospective database analysis to assess clinical management and costs in England.

BACKGROUND: Dupuytren's disease is a fibro-proliferative disorder affecting ~3-5% of the UK population. Current surgical treatments for Dupuytren's contracture (DC) include fasciectomy and fasciotomy. We assessed the clinical management of DC in England over a 5-year period; associated NHS costs were assessed for a 1-year period. METHODS: Hospital Episode Statistics were extracted from April 2003 to March 2008 for patients with Palmar Fascial Fibromatosis (ICD10=M720) and DC-related procedures. Variables included demographics, OPCS, patient status and physician specialty. To estimate 2010-2011 costs, HRG4 codes and the National Schedule of Tariff 2010-11-NHS Trusts were applied to the 2007-2008 period. RESULTS: Over 5 years, 75,157 DC admissions were recorded; 64,506 were analyzed. Mean admissions per year were 12,901 and stable. Day cases increased from 42% (2003-2004) to 62% (2007-2008). The percent of patients having two or more admissions per year increased from 5.5% in 2003-2004 to 26.1% in 2007-2008. Between 2003 and 2007, 91% of procedures were Fasciectomy. Revision of Fasciectomy and Fasciotomy each accounted for ~4%; Amputation for 1%. In 2007, classification was extended to identify Digital Fasciectomy, its Revision and Dermofasciectomy. In 2007-2008, admissions were: 70% Palmar Fasciectomy, 16% Digital Fasciectomy, 1.3% Other Fasciectomy, 4.4% Revision of Palmar Fasciectomy, 1.3% Revision of Digital Fasciectomy, 3.8% Division of Palmar Fascia, 2.6% Dermofasciectomy and 1.1% Amputation. 79% of cases were overseen by trauma and orthopaedic surgeons, 19% by plastic surgeons. Mean (±SD) inpatient hospital length of stay was 1.5 (±1.4) days in 2003-2004 and 1.0 (±1.3) days in 2007-2008. Total estimated costs for 1 year (2010-2011) were £41,576,141. Per-patient costs were £2,885 (day case) and £3,534 (inpatient). Costs ranged from £2,736 (day-case Fasciectomy) to £9,210 (day-case Revision Digital). CONCLUSIONS: Between 2003 and 2008, fasciectomy was the most common surgical procedure for DC in England. While procedure rates and physician specialties varied little, there was a reversal in surgical venue: inpatient operations decreased as day-case procedures increased. The change is likely due to economic trends and changes to the healthcare system. Estimated costs for 2010-2011 varied by procedure type and patient status. These findings can be used to understand clinical management of DC and guide healthcare policy.

Relationship Among Treatment, Pruritus, Investigator's Static Global Assessment, and Quality of Life in Patients with Atopic Dermatitis.

INTRODUCTION: The Investigator's Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies. METHODS: Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model. RESULTS: Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: - 0.68) and small for vehicle (ES: - 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%). CONCLUSIONS: These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL.

Adherence to aldosterone-blocking agents in patients with heart failure.

The use of aldosterone blockers in the pharmacologic therapy for heart failure (HF) in patients with left ventricular systolic dysfunction has been shown to significantly reduce overall mortality, sudden cardiac death, and hospitalization. Patient adherence to polypharmaceutical regimens including aldosterone blockade and other key medication components is a concern for clinicians and their patients. A retrospective cohort study was conducted using integrated US pharmacy/medical claims covering 44.5 million lives. Inclusion criteria included the following: age at least 50 years, newly prescribed spironolactone or eplerenone from 2002 to 2006, with HF diagnosis within 12 months of prescription initiation and follow-up of at least 6 months to assess outcomes (12 months for adherence). Compliance was measured as the proportion of days covered (prescription days supply in the first year postindex for 365 days), and persistence was measured as days from the first to the last prescription. Of 388,523 patients with HF, 60,183 patients (15.5%) received an aldosterone blocker (n = 2024 for eplerenone, n = 58,159 for spironolactone), from which a newly treated subset was studied (n = 568 eplerenone, n = 11,982 spironolactone). Proportion of days covered was significantly greater for eplerenone (79% ± 42%) than for spironolactone (66% ± 42%, P < 0.01). Persistence was significantly higher for eplerenone than for spironolactone (P < 0.01) with discontinuation before 1 year at 49.5% and 73.7%, respectively. This analysis shows that a majority of patients did not receive an aldosterone blocker after HF diagnosis despite cardiovascular event risks and raises the hypothesis that eplerenone is associated with higher compliance and persistence as compared with spironolactone.

Comparison of methods for delivering a lifestyle modification program for obese patients: a randomized trial.

BACKGROUND: Physicians frequently prescribe medications for weight loss but offer minimal lifestyle counseling despite the additional benefits of combining both interventions. OBJECTIVE: To compare 5 methods of delivering a lifestyle modification program to obese patients receiving sibutramine. DESIGN: Randomized, 6-month, open-label study. Participants were assigned to intervention groups by using a computer-generated schedule of randomly permuted blocks. Block length was 5. SETTING: 12 independent research clinics with experience running obesity trials. PATIENTS: 376 patients with obesity (body mass index > or =30 and <40 kg/m(2)). INTERVENTION: High-frequency face-to-face lifestyle modification counseling (HF-F2F) (n = 74), low-frequency face-to-face counseling (LF-F2F) (n = 76), high-frequency telephone counseling (HF-TEL) (n = 76), high-frequency e-mail counseling (HF-EMAIL) (n = 74), or no dietitian contact (self-help [SELF]) (n = 76). All participants received sibutramine, 10 mg/d; a lifestyle manual; and access to a weight-loss Web site. MEASUREMENTS: Percentage change in body weight at 6 months was the primary outcome. Secondary end points included changes in waist circumference; lipid, glucose, and insulin levels; blood pressure; weight-related symptoms; and quality of life at 6 months. RESULTS: At 6 months, the mean weight loss, relative to baseline, in the HF-F2F and HF-TEL groups was similar (8.9% [95% CI, 8.0% to 9.8%] and 7.7% [CI, 6.8% to 8.7%]) and significantly greater than that in the other groups (LF-F2F, 6.4% [CI, 5.4% to 7.3%]; HF-EMAIL, 5.9% [CI, 5.0% to 6.8%]; and SELF, 5.2% [CI, 4.3% to 6.1%]). All groups showed significant improvements in waist circumference, high-density lipoprotein cholesterol and triglyceride levels, and measures of quality of life and weight-related symptoms. There were no serious adverse events and no differences in minor events among groups. LIMITATION: Most participants were women, and the attrition rate was 30%. CONCLUSION: High-frequency telephone contact with a dietitian was similar to HF-F2F contact for supporting lifestyle modification in obese patients trying to lose weight. The findings might be used by providers and health systems to promote healthy lifestyle changes for their patients. FUNDING: Pfizer Global Research and Development.

Tofacitinib in the treatment of moderate-to-severe rheumatoid arthritis: a cost-effectiveness analysis compared with adalimumab in Taiwan.

Aims: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis investigated the cost-effectiveness of the second-line treatment with tofacitinib, compared with adalimumab, both plus methotrexate (MTX), in patients with moderate-to-severe RA and an inadequate response to the first-line MTX, from a Taiwan National Health Insurance Administration perspective. Materials and methods: A patient-level simulation model was used to project lifetime costs and quality-adjusted life-years (QALYs). Base-case analysis compared second-line treatment with tofacitinib 5 mg twice daily plus MTX vs adalimumab 40 mg every 2 weeks plus MTX. Patients switched or discontinued treatment due to a lack or loss of effectiveness or a serious adverse event. Efficacy was measured by change in Health Assessment Questionnaire-Disability Index (HAQ-DI) score. HAQ-DI scores were used to predict mortality and resource utilization, and were mapped onto utility values to estimate QALYs. Efficacy and safety data were derived from clinical trials and other secondary sources. Uncertainty in model parameters was explored using one-way deterministic and probabilistic sensitivity analyses. Results: Patients gained 0.09 more QALYs with second-line tofacitinib plus MTX compared with adalimumab plus MTX (5.13 vs 5.04, respectively) at an additional cost of New Taiwan Dollars (NT$) 12,881. The incremental cost-effectiveness ratio was NT$143,122/QALY. One-way sensitivity analysis confirmed the base-case result was robust. Limitations: The lack of available clinical data, particularly for HAQ-DI scores, may introduce some bias in the analysis. No patients were in an early stage of RA, which may limit the generalizability of these results. Base-case results from our study are not necessarily generalizable to countries with healthcare systems that differ considerably from Taiwan. Conclusions: From a payer perspective, second-line treatment with tofacitinib plus MTX is a cost-effective treatment strategy, compared with adalimumab plus MTX, in patients with moderate-to-severe RA in Taiwan.

Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis.

INTRODUCTION: No published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data. METHODS: This observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016. Efficacy outcomes at 6 months included modified American College of Rheumatology 20% responses, Clinical Disease Activity Index (CDAI) and Pain. Outcomes were compared between patients receiving TNFi and tofacitinib with or without MTX and by line of therapy. Outcomes within therapy lines were compared using propensity-score matching; between-group differences were estimated using mixed-effects regression models. RESULTS: Patients receiving tofacitinib had longer RA duration and a greater proportion had previously received biologics than those receiving TNFi; other baseline characteristics were comparable. In patients receiving second- and third-line TNFi therapy, CDAI low disease activity/remission response rates were significantly better with concomitant MTX. Too few patients received tofacitinib as second line for meaningful assessment. No significant differences were observed in outcomes between tofacitinib as monotherapy and tofacitinib with concomitant MTX. CONCLUSIONS: In clinical practice, TNFi efficacy is improved with concomitant MTX in the second and third line. In the third/fourth line, patients are likely to achieve similar efficacy with tofacitinib monotherapy, or TNFi or tofacitinib in combination with MTX. FUNDING: Pfizer Inc.

The Challenge of Managing Atopic Dermatitis in the United States.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease that affects up to 13% of children and 10% of adults in the United States. Among patients and their families, atopic dermatitis has a considerable effect on quality of life and represents a substantial economic burden. OBJECTIVE: To describe the impact and challenges of atopic dermatitis and to provide nondermatologists in the healthcare community an enhanced understanding of atopic dermatitis to facilitate treatment and pharmacy benefit discussions. DISCUSSION: Atopic dermatitis is a heterogeneous disease, and its diagnosis is hampered by a lack of objective diagnostic criteria. The current management guidelines address the distinct clinical phenotypes as a single disease and do not incorporate recent clinical advances, such as the targeting of specific inflammatory processes. The treatment guidelines for atopic dermatitis are complex and challenge healthcare providers, patients, and caregivers. Novel treatments can provide additional therapeutic options for patients with atopic dermatitis. CONCLUSIONS: Treatment options for atopic dermatitis are expanding with the development of novel anti-inflammatory therapies. An increased understanding of these advancements is necessary to optimize care for patients with atopic dermatitis.

Burden of atopic dermatitis in Asia.

Atopic dermatitis is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions. It is considered one of the most common chronic conditions, with an estimated global prevalence of nearly 230 million. As in the rest of the world, prevalence of atopic dermatitis has been increasing in Asian countries over the last few decades. This increased prevalence in Asian countries has been attributed to factors such as rapid urbanization, increasingly Westernized lifestyles, and improved standards of living and education. As a result, it is important to understand the increasing burden of disease in Asian countries and the differences between the countries in terms of epidemiology, diagnostic criteria, management, quality of life and economic burden.

Development and validation of the WEll-being and Satisfaction of CAREgivers of Children with Diabetes Questionnaire (WE-CARE).

BACKGROUND: This study was designed to develop a diabetes-specific questionnaire on parents' quality of life and satisfaction with their child's diabetes treatment, the WEll-being and Satisfaction of CAREgivers of Children with Diabetes Questionnaire, and to conduct psychometric validation of the WE-CARE. METHODS: Parents of 116 children aged 6 to 11 years were enrolled in the United States. Children had type 1 diabetes mellitus for > 1 year, had been treated with subcutaneous insulin for > or = 2 months, and had a recent glycosylated hemoglobin (HbA1C) measurement. Recruiting clinicians provided clinical information on the children. Over a two-week period, parents completed WE-CARE (initial 68 items) and two other questionnaires (the 36-item Short Form of the Medical Outcomes Study and the 50-item Child Health Questionnaire-Parent Form) twice. RESULTS: A literature review and one-on-one interview with caregivers and pediatricians led to the development of a draft questionnaire consisting of 68 items. Factor analysis suggested retention of 37 of the 68 initial items grouped into four multi-item scales (Psychosocial Well-being, Ease of Insulin Use, Treatment Satisfaction, and Acceptance of Insulin Administration as well as a Total Score). The four multi-item domains of WE-CARE were found to be psychometrically robust - they had negligible floor and ceiling effects, excellent internal consistency and test-retest reliability, high item-discriminant validity and good concurrent, divergent, known-group and clinical validity. Moderate interscale correlations among the four WE-CARE domains indicated that the concepts they measure were related but distinct. CONCLUSION: These data suggest that WE-CARE provides a reliable and valid measure of parents' well-being and treatment satisfaction related to their child's diabetes. While these results show promise, additional validation of WE-CARE is warranted.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis After Methotrexate or After 1 or 2 TNF Inhibitors from a U.S. Payer Perspective.

BACKGROUND: Treatment cycling with biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors (TNFi), is common among patients with rheumatoid arthritis (RA) and can result in reduced clinical efficacy and increased economic burden. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. OBJECTIVE: To evaluate and compare the economic effect of tofacitinib 5 mg twice daily (BID) treatment directly after methotrexate (MTX) in the MTX-inadequate responder population, or after MTX and 1 TNFi (adalimumab [ADA] or etanercept [ETN]) or 2 TNFi (ADA and ETN) in TNF-inadequate responder patients with RA, from a U.S. payer perspective. METHODS: A decision-tree economic model was used to evaluate costs over 2 years. Treatment response was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR response rates at 6-month intervals were derived from U.S. prescribing information for monotherapy and combination therapy. Safety event rates were sourced from a meta-analysis. It was assumed that 75% of patients switched therapy after an adverse event or lack of response. Cost inputs included drugs, monitoring and administration (including physician visits), health care utilization, and treatment for adverse events. The population comprised all organization members (i.e., RA and non-RA members); RA patients receiving TNFi were estimated using epidemiologic data. Results were based on an organization size of 1 million. Economic endpoints were total 2-year costs, costs per member per month (PMPM), and costs per ACR20/50 responder. RESULTS: 1,321 patients were included for analysis. Based on ACR20 switch criteria and either 100% or 50% monotherapy rates for all treatments, total 2-year costs and costs PMPM were lower for patients receiving tofacitinib as second-line therapy after MTX and as third-line therapy after MTX and 1 TNFi; costs were highest for patients who cycled through 2 TNFi. Similar trends were observed for switch criteria based on ACR50 response and addition of 20% rebates for ADA and ETN and 0% for tofacitinib, although differences were mitigated slightly. CONCLUSIONS: A treatment strategy with tofacitinib as either second- or third-line therapy after MTX may be a lower cost treatment option, compared with fourth-line introduction of tofacitinib after cycling through 2 TNFi following MTX. DISCLOSURES: All aspects of this study were funded by Pfizer. Claxton was an employee of York Health Economics Consortium, University of York, at the time of this study. Taylor is an employee of York Health Economics Consortium, The University of York, which received funding from Pfizer to conduct this study. Soonasra, Bourret, and Gerber are employees of Pfizer and hold stock/stock options in Pfizer. A previous iteration of the data reported in this manuscript (before adjustment for recent drug price increases) was presented at the Academy of Managed Care Pharmacy 28th Annual Meeting and Expo; April 19-22, 2016; held in San Francisco, CA.

Topical treatment utilization for patients with atopic dermatitis in the United States, and budget impact analysis of crisaborole ointment, 2.

BACKGROUND: Atopic dermatitis (AD), a chronic inflammatory skin disease, is often treated with topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI). Crisaborole ointment is a non-steroidal, phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In December 2016, crisaborole was approved in the US for mild-to-moderate AD in patients ≥2 years of age. AIMS: To evaluate real-world utilization and cost of TCS and TCI in the US and estimate the budget impact of crisaborole over 2 years from a third-party payer perspective. METHODS: TCS and TCI prescriptions in 2015 for patients ≥2 years of age with ≥1 AD diagnosis in the Truven Health Analytics MarketScan Commercial and Medicare Supplemental Research Databases were analyzed for patients receiving TCI or TCS alone or in combination (TCS/TCI population) and patients receiving TCI alone or in combination with TCS (TCI population). A budget impact model used TCS and TCI market shares, annual use, and cost per prescription. Crisaborole uptake rates of 4.7% (TCS) and 20.2% (TCI), with an annual increase of 1% in year 2, were assumed. Budget impact was calculated as total and per-member-per-month (PMPM) cost over 2 years for a health plan of 1 million members. RESULTS: Annual prescriptions/patient ranged from 1.36-6.41; annual cost/patient was $53-$1,465. The budget impact of crisaborole over 2 years in the TCS/TCI population was $350,946 (PMPM, $0.015), with increases of $162,106 in year 1 (PMPM, $0.014) and $188,841 in year 2 (PMPM, $0.016). The budget impact in the TCI population was -$22,871, with decreases of $11,160 in year 1 and $11,712 in year 2 (each PMPM, -$0.001). For both populations, one-way sensitivity analyses showed that budget impact was most sensitive to changes in crisaborole cost and annual use. CONCLUSIONS: From US payer perspectives, adoption of crisaborole results in modest pharmacy budget impact/savings.

Modelling the cost-effectiveness of tofacitinib for the treatment of rheumatoid arthritis in the United States.

BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) is a chronic, debilitating disease affecting an estimated 1.5 million patients in the US. The condition is associated with a substantial health and economic burden. An economic model was developed to evaluate the cost-effectiveness of tofacitinib (a novel oral Janus kinase inhibitor) versus biologic therapies commonly prescribed in the US for the treatment of RA. METHODS: A cost-utility model was developed whereby sequences of treatments were evaluated. Response to treatment was modeled by HAQ change, and informed by a network meta-analysis. Mortality, resource use and quality of life were captured in the model using published regression analyses based on HAQ score. Treatment discontinuation was linked to response to treatment and to adverse events. Patients were modeled as having had an inadequate response to methotrexate (MTX-IR), or to a first biologic therapy (TNFi-IR). RESULTS: The tofacitinib strategy was associated with cost savings compared with alternative treatment sequences across all modeled scenarios (i.e. in both the MTX-IR and TNFi-IR scenarios), with lifetime cost savings per patient ranging from $65,205 to $93,959 (2015 costs). Cost savings arose due to improved functioning and the resulting savings in healthcare expenditure, and lower drug and administration costs. The tofacitinib strategies all resulted in an increase in quality-adjusted life years (QALYs), with additional QALYs per patient ranging from 0.01 to 0.22. CONCLUSIONS: Tofacitinib as a second-line therapy following methotrexate failure and as a third-line therapy following a biologic failure produces lower costs and improved quality of life compared with the current pathway of care.

Patient impact and economic burden of mild-to-moderate atopic dermatitis.

OBJECTIVE: To present a systematic review of studies conducted to evaluate patient impact and economic burden of mild-to-moderate atopic dermatitis. METHODS: A MEDLINE (via PubMed), Excerpta Medica database (Embase), and Cochrane Library search for English-language articles published January 1, 1996-December 31, 2016 was performed. Abstracts were manually reviewed from 2015-2016 from 10 leading conferences and congresses associated with atopic dermatitis. Manuscripts were reviewed for inclusion in two main categories within the review: patient impact of mild-to-moderate atopic dermatitis and economic burden of atopic dermatitis. Excluded from this dataset were any patients in these studies who had severe atopic dermatitis, moderate-to-severe atopic dermatitis, or atopic dermatitis of unspecified severity. RESULTS: In total, 222 studies qualified for inclusion in the analysis; this report focuses on the 76 studies that reported results stratified by disease severity. Measured by general and specific instruments, even mild-to-moderate atopic dermatitis reduces the overall quality-of-life of patients and their caregivers/families. Disease severity assessed by validated severity instruments directly correlated with quality-of-life. Treatment of atopic dermatitis can improve the quality-of-life of patients and their caregivers/families by alleviation of symptoms and reduction in severity. In general, total costs increased as disease severity increased; even mild atopic dermatitis imposed substantial costs. CONCLUSIONS: The results emphasize the impact of atopic dermatitis, especially mild atopic dermatitis, on patient lives and finances, including education of clinicians, payers, and patients regarding benefits associated with treatment adherence.

Delayed Treatment Acceleration in Patients with Rheumatoid Arthritis Who Have Inadequate Response to Initial Tumor Necrosis Factor Inhibitors: Data from the Corrona Registry.

BACKGROUND: The implementation of treat-to-target principles in rheumatoid arthritis (RA) has not been fully investigated in patients with inadequate response to tumor necrosis factor (TNF) inhibitor treatment. OBJECTIVES: To evaluate the prevalence of an inadequate response to initial TNF inhibitor treatment at 6 and 12 months among patients with RA in a real-world patient registry, as well as the delay in therapy adjustment and its impact on disease activity and patient-reported outcome (PRO) measures. METHODS: This analysis is based on data of patients with moderate or severe disease activity (Clinical Disease Activity Index [CDAI] score >10) who were included in the Consortium of Rheumatology Researchers of North America (Corrona) RA registry, a prospective, observational database. The patients had never received treatment with a biologic disease-modifying antirheumatic drug (DMARD) and had initiated treatment with a TNF inhibitor (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between October 2001 and December 2014. We evaluated treatment response (CDAI score ≤10), select PRO measures, and treatment changes at 6 months. Patients who had an inadequate response to TNF inhibitor therapy at 6 months and continued to use their initial TNF inhibitor were evaluated again at 12 months. RESULTS: This retrospective analysis included 2282 patients. At 6 months, 1732 (75.9%) of the patients continued to use their initial TNF inhibitor; of these, 803 (46.4%) patients had an inadequate response to treatment. Of the 803 patients who had an inadequate response at 6 months, 488 (60.8%) continued their initial treatment at 12 months. Of these 488 patients, 315 (64.5%) had an inadequate response at 12 months, and 173 (35.5%) had a response. Numerically greater improvements in all PRO measures were observed for patients who responded to therapy compared with patients with an inadequate response. CONCLUSIONS: In this real-world analysis of data from the Corrona RA registry, a considerable proportion of patients with RA had an inadequate response to the initial TNF inhibitor therapy at 6 and 12 months. Many patients continued to have moderate or high disease activity, without accelerating treatment (eg, addition or increase in the dose of concurrent conventional synthetic DMARDs or a TNF inhibitor), contrary to treat-to-target principles, thus remaining at risk for accumulating joint damage and disability.

Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network Meta-Analysis.

Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015. Efficacy data based on American College of Rheumatology (ACR) response criteria, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI) at 6 months, and discontinuation rates due to adverse events were analyzed by means of Bayesian NMAs. Results. 45 RCTs were identified, the majority of which demonstrated a low risk of bias. Tofacitinib 5 mg twice daily (BID) and 10 mg BID monotherapy exhibited comparable efficacy and discontinuation rates due to adverse events versus other monotherapies. Tofacitinib 5 mg BID and 10 mg BID + DMARDs or methotrexate (MTX) were mostly comparable to other combination therapies in terms of efficacy and discontinuation due to adverse events. Conclusion. In most cases, tofacitinib had similar efficacy and discontinuation rates due to adverse events compared to biologic DMARDs.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis: Modeling the Cost of Treatment Strategies in the United States.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib is approved in the United States for use in adults with moderately to severely active RA and an inadequate response or intolerance to methotrexate. OBJECTIVES: To (a) evaluate, using an economic model, the treatment costs of an RA strategy including tofacitinib, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic RA treatment strategies, which are commonly prescribed in the United States, and (b) assess the economic impact of monotherapy and combination therapy in patients who had an inadequate response to methotrexate therapy (MTX-IR analysis) and to combination therapy in patients who had an inadequate response to a tumor necrosis factor inhibitor (TNF-IR analysis). METHODS: A transparent, Excel-based economic model with a decision-tree approach was developed to evaluate costs over a 1- and 2-year time horizon. The model compared tofacitinib 5 mg twice a day (BID) either as monotherapy or in combination with MTX with similarly labeled biologic therapies. Response to treatment was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR20 represented clinical response and determined whether patients continued therapy. ACR response rates at 6-month intervals were sourced from prescribing information and safety event rates from a published meta-analysis. Following an adverse event or a lack of response to treatment, it was assumed that 75% of patients switched to the next line of treatment (first to abatacept and then to rituximab). The perspective was that of a U.S. payer. Costs were reported in 2015 U.S. dollars and included drug wholesale acquisition costs, monitoring, drug administration, and treatment for minor and serious adverse events. The patient population eligible for treatment was based on the total number of members (i.e., RA and non-RA) in a payer organization; members with RA treated with biologic therapies were estimated using epidemiological data. Sensitivity analyses were conducted to explore the impact of varying key parameters, including treatment-switching probability, product rebate, major rates of adverse drug reaction, and ACR20 rates, on the model outcomes. RESULTS: Tofacitinib combination therapy after MTX failure was associated with the lowest cost per member per month (PMPM) over a 2-year time frame at $5.53, compared with $6.49 for adalimumab, $6.43 for etanercept, $5.95 for certolizumab, and $5.89 for tocilizumab. Similar savings were observed when all biologics were administered as monotherapy. Tofacitinib combination therapy was also associated with the lower PMPM cost compared with adalimumab combination therapy in the TNF-IR analysis. Tofacitinib was also among the lowest cost per ACR20 responder in each analysis. Sensitivity analyses demonstrated that tofacitinib would potentially be cost saving even in the least optimistic scenarios. CONCLUSIONS: This analysis suggests that tofacitinib 5 mg BID following MTX failure is a lower cost per patient treatment option when used either as monotherapy or combination therapy, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic regimens. Tofacitinib + MTX in TNF-IR patients was also predicted to be a lower-cost treatment option compared with adalimumab+MTX and was associated with the lowest cost per ACR 20/50/70 responder. DISCLOSURES: This study was funded by Pfizer, which determined the research topic and paid York Health Economics Consortium to develop the analysis and conduct the research. York Health Economics Consortium has received consultancy fees from Pfizer. Gerber, Wallenstein, Mendelsohn, Bourret, Singh, and Moynagh are employees and shareholders of Pfizer. Editorial support was funded by Pfizer and was provided by Claxton, Jenks, and Taylor, who are employees of York Health Economics Consortium. Study concept and design were contributed primarily by Taylor, Jenks, Gerber, and Singh, along with the other authors. Gerber, Moynagh, and Singh collected the data, assisted by Bouret and Mendelsohn; data interpretation was performed by Claxton, Gerber, Bouret, and Mendelsohn. The manuscript was written primarily by Claxton, with assistance from the other authors, and revised by Claxton, Gerber, Bouret, and Mendelsohn, with assistance from the other authors.

Real-world trials to answer real-world questions.

Currently, there is a discrepancy between clinical trials designed to assess the efficacy and safety of a new medication under investigation and the real-life questions that need to be addressed regarding the clinical use of the medication by patients, healthcare professionals and society. The data necessary to obtain regulatory approval may be of limited relevance to policy makers when calculating economic parameters such as value for money or cost effectiveness. 'Real-world' studies examine questions relevant to health policy and reimbursement. There are many different forms of clinical trials, but in designing trials incorporating realistic budget impact estimates the important issue is to ensure we are asking a sensible question and attempting to answer it with an appropriate experimental design. As an example, a real-world trial currently underway that examines scenarios of introducing inhaled insulin into clinical practice is described.