Efficacy and safety of upadacitinib for 16-week extended induction and 52-week maintenance therapy in patients with moderately to severely active ulcerative colitis.

BACKGROUND: Upadacitinib is an oral, selective Janus kinase inhibitor. AIM: To assess the efficacy and safety of upadacitinib in patients with moderate-to-severe ulcerative colitis following 16-week extended induction therapy, and 52-week maintenance therapy in patients achieving clinical response after 16-week extended induction therapy METHODS: Patients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re-randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52-week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout. RESULTS: Overall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib. CONCLUSIONS: Patients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy. CLINICAL TRIAL REGISTRATION: NCT02819635; NCT03653026.

Content Validity and Psychometric Evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Patients with Crohn's disease (CD) or ulcerative colitis (UC) frequently experience fatigue, although it is often overlooked in medical research and practice. AIMS: To explore patients' experience of fatigue and evaluate content validity, psychometric properties, and score interpretability of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in patients with CD or UC. METHODS: Concept elicitation and cognitive interviews were conducted with participants aged ≥ 15 years with moderately-to-severely active CD (N = 30) or UC (N = 33). To evaluate psychometric properties (reliability and construct validity) and interpretation of FACIT-Fatigue scores, data from two clinical trials were analyzed [ADVANCE (CD): N = 850; U-ACHIEVE (UC): 248]. Meaningful within-person change was estimated using anchor-based methods. RESULTS: Almost all interview participants reported experiencing fatigue. Over 30 unique fatigue-related impacts were reported per condition. The FACIT-Fatigue was interpretable for most patients. FACIT-Fatigue items had good internal consistency (Cronbach's α 0.86-0.88 for CD and 0.94-0.96 for UC); the total score displayed acceptable test-retest reliability (intraclass correlation coefficients > 0.60 for CD and > 0.90 for UC). FACIT-Fatigue scores had acceptable convergent validity with similar measures. A 7-10 point improvement for CD and 4-9 point improvement for UC on the FACIT-Fatigue total score may represent meaningful improvements. CONCLUSIONS: These results highlight the importance of fatigue among adolescents and adults with CD or UC and provide evidence that the FACIT-Fatigue is content valid and produces reliable, valid, and interpretable scores in these populations. Care should be taken if using the questionnaire with adolescents who may be less familiar with the word "fatigue." Clinical trial registration numbers NCT03105128 (date of registration: 4 April 2017) and NCT02819635 (date of registration: 28 June 2016).

Outcomes Following Adalimumab Bio-originator to Biosimilar Switch-A Comparison Using Real-world Patient- and Physician-Reported Data in European Countries.

INTRODUCTION: The aim of this work is to compare real-world outcomes of patients with rheumatoid arthritis (RA) receiving adalimumab (ADA) bio-originator (non-switchers) to those who had switched from ADA bio-originator to an ADA biosimilar (switchers) on the basis of the hypothesis that these outcomes would differ. METHODS: Data were drawn from the Adelphi RA Disease Specific Programme™, a point-in-time survey of physicians and their patients in Europe (France, Germany, Italy, Spain, UK) in 2020. Physicians completed a questionnaire for their next ten adult patients with RA, followed by four additional patients who had switched from ADA bio-originator to an ADA biosimilar (switchers). Physician- and patient-reported outcomes (PROs) for switchers and non-switchers were compared by propensity score matching. RESULTS: Three hundred and three rheumatologists provided data for 160 non-switchers and 225 switchers, 140 patients provided data; 51 non-switchers, 89 switchers. According to physician-reported disease activity, non-switchers were more likely to improve on their current ADA treatment than switchers (68%, n = 108 vs. 26%, n = 59 p < 0.001) and less likely to worsen (1%, n = 2 vs. 9%, n = 20; p < 0.01). Physician-reported patient adherence was significantly lower amongst switchers versus non-switchers (0.66 vs. 0.78, respectively; p = 0.04). More non-switchers than switchers were reported by their physicians to be consistent in taking their RA medicine (p < 0.001). Compared with non-switchers, PRO measures indicated quality of life was worse (EQ-5D Visual Analogue Scale: 62.9 vs. 71.9; p < 0.001) and activity impairment was greater (Work Productivity Activity Index: 31.0 vs. 24.4; p = 0.02) for switchers, with trends for poorer health status and greater pain. CONCLUSIONS: Non-medical switching in RA treatment may lead to unforeseen outcomes that should be considered by health decision-makers.

Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment.

BACKGROUND & AIMS: We evaluated the efficacy of once-daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis (UC). Post hoc analyses were performed on pooled data from 2 replicate, phase 3, multicenter induction trials, U-ACHIEVE Induction and U-ACCOMPLISH, to determine the earliest time point of efficacy onset. METHODS: Diary entry data through 14 days from the first dose of placebo or upadacitinib 45 mg QD were analyzed for daily improvement in UC symptoms (stool frequency, rectal bleeding, abdominal pain, and bowel urgency). Changes in inflammatory markers, high-sensitivity C-reactive protein (hs-CRP), and fecal calprotectin (FCP) were assessed at week 2 and quality of life (QoL) at weeks 2 and 8. Regression analysis determined the association between changes in UC symptoms and the likelihood of achieving clinical remission/response per Adapted Mayo score at week 8. RESULTS: Overall, 988 patients (n = 328 placebo, n = 660 upadacitinib) were analyzed. Patients treated with upadacitinib demonstrated significant improvements vs placebo in all UC symptoms between days 1 and 3 and maintained through day 14. A >50% reduction from baseline in hs-CRP and FCP levels was achieved by 75.7% and 48.2% of patients, respectively (P < .001 vs placebo). Increased rates of clinical remission/response per Partial Mayo score from week 2 (26.9%/59.4% upadacitinib 45 mg QD vs 4.3%/22.3% placebo, P < .001) and significant improvements in QoL at weeks 2 and 8 were observed. Early improvement in stool frequency and bowel urgency by day 3 and reductions in hs-CRP and FCP by week 2 were significantly associated with clinical remission/response at week 8. CONCLUSIONS: Upadacitinib 45 mg QD provided rapid relief of UC symptoms from day 1. CLINICALTRIALS: gov: U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026).

Timing of elimination of hepatitis C virus in Canada's provinces.

BACKGROUND: Infection with chronic hepatitis C virus is a global public health concern. A recent study concluded that Canada is on track to achieve hepatitis C elimination goals set by the World Health Organization if treatment levels are maintained. However, recently a falling temporal trend in treatments in Canada was observed, with most provinces seeing a decrease before the global coronavirus pandemic. This study assesses the timing of elimination of hepatitis C in the 10 provinces of Canada. METHODS: Previously published disease and economic burden model of hepatitis C infection was populated with the latest epidemiological and cost data for each Canadian province. Five scenarios were modelled: maintaining the status quo, decreasing diagnosis and treatment levels by 10% annually, decreasing diagnosis and treatment levels by 20% annually, increasing them by 10% annually, and assuming a scenario with no post-coronavirus pandemic recovery in treatment levels. Year of achieving hepatitis C elimination, necessary annual treatments for elimination, and associated disease and economic burden were determined for each province. RESULTS: If status quo is maintained, Manitoba, Ontario, and Québec are off track to achieve hepatitis C elimination by 2030 and would require 540, 7,700, and 2,800 annual treatments, respectively, to get on track. Timely elimination would save 170 lives and CAD $122.6 million in direct medical costs in these three provinces. CONCLUSIONS: Three of Canada's provinces-two of them the most populous in the country-are off track to achieve the hepatitis C elimination goal. Building frameworks and innovative approaches to prevention, testing, and treatment will be necessary to achieve this goal.

A tool to measure the impact of inaction toward elimination of hepatitis C: A case study in Korea.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) and its sequelae present a significant source of economic and societal burden. Introduction of highly effective curative therapies has made HCV elimination attainable. The study used a predictive model to assess the clinical and economic impact of implementing national screening and treatment policies toward HCV elimination in Korea. METHODS: A previously validated Markov disease progression model of HCV infection was employed to analyze the clinical and economic impact of various strategies for HCV diagnosis and treatment in Korea. In this analysis, the model compared the clinical and economic outcomes of current HCV-related interventions in Korea (7,000 patients treated and 4,200 patients newly diagnosed annually, starting in 2017) to four elimination scenarios: 1) initiating sufficient diagnosis and treatment interventions to meet the World Health Organization's GHSS elimination targets by 2030, 2) delaying initiation of interventions by one year, 3) delaying initiation of interventions by two years and 4) accelerating initiation of interventions to meet elimination targets by 2025. Modelled historical incidence of HCV was calibrated to match a viremic HCV prevalence of 0.44% in 2009. Elimination scenarios required 24,000 treatments and 34,000 newly diagnosed patients annually, starting in 2018, to reach the 2030 targets. RESULTS: Compared to current "status quo" interventions, elimination (or accelerated elimination by 2025) would avert 23,700 (27,000) incident cases of HCV, 1,300 (1,400) liver-related deaths (LRDs) and 2,900 (3,100) cases of end-stage liver disease (ESLD) over the 2017-2030 time period. Postponing interventions by one (or two) years would avert 21,100 (18,600) new HCV infections, 920 (660) LRDs and 2,000 (1,400) cases of ESLD by 2030. Following elimination or accelerated elimination strategies would save 860 million USD or 1.1 billion USD by 2030, respectively, compared to the status quo, requiring an up-front investment in prevention that decreases spending on liver-related complications and death. CONCLUSIONS: By projecting the impact of interventions and tracking progress toward GHSS elimination targets using modelling, we demonstrate that Korea can prevent significant morbidity, mortality and spending on HCV. Results should serve as the backbone for policy and decision-making, demonstrating how aggressive prevention measures are designed to reduce future costs and increase the health of the public.

Cost-Effectiveness Analysis of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin Regimen for Patients Infected With Chronic Hepatitis C Virus Genotype 1 in Malaysia.

OBJECTIVES: The combination of pegylated-interferon and ribavirin (PegIFN+RBV) is currently the gold standard in treating chronic hepatitis C virus (HCV) patients in Malaysia and is reimbursed by the Malaysian authorities. This analysis evaluated the cost-effectiveness (CE) of the ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin (OBT/PTV/r+DSB±RBV) regimen as compared with the PegIFN+RBV or no treatment in chronic HCV Genotype 1 (GT1) treatment-naïve and treatment-experienced cirrhotic and noncirrhotic patients in Malaysia. METHODS: A Markov model based on previously published CE models of HCV was adapted for the Malaysian public healthcare payer perspective, based on good modeling practices. Treatment attributes included efficacy, regimen duration, and EQ-5D treatment-related health utility. Transitional probabilities and health state health utilities were derived from previous studies. Costs were derived from Malaysian data sources. Costs and outcomes were discounted at 3.0% per year. Deterministic and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainties around key variables. RESULTS: Based on the analysis, patients treated with the OBT/PTV/r+DSB±RBV showed less frequent progression to compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths when compared with standard care (ie, PegIFN+RBV or no treatment). At a price of MYR 1846/day, the OBT/PTV/r+DSB±RBV regimen is cost-effective over PegIFN+RBV and yields better outcomes in terms of life-years (LYs) gained and quality-adjusted life-years (QALYs) at a higher cost, which is still well below the implied willingness to pay threshold of MYR 384 503/QALY. CONCLUSION: The OBT/PTV/r+DSB±RBV regimen is cost-effective for treatment naïve, treatment experienced, cirrhotic, and noncirrhotic GT1 chronic HCV patients in Malaysia.

Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents With Chronic Hepatitis C Virus: Part 1 of the DORA Study.

The pangenotypic regimen of glecaprevir and pibrentasvir (G/P) is approved to treat adults with chronic hepatitis C virus (HCV) infection and has yielded high cure rates in adults in clinical trials. Approved treatment options for pediatrics may include ribavirin. A pangenotypic regimen for pediatric patients remains an unmet need. DORA is an ongoing phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in pediatric patients with chronic HCV. This analysis includes Part 1 of the study, conducted in adolescent patients 12-17 years of age given the adult regimen of G/P (300 mg/120 mg) once daily for 8-16 weeks according to the indication durations used in adults. Patients were either treatment naïve or experienced with interferon-based regimens. The primary PK endpoint was steady-state exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12). The secondary efficacy endpoints were on-treatment virologic failure, relapse, and reinfection. Safety and tolerability were monitored. Part 1 enrolled 48 adolescent patients infected with genotypes 1, 2, 3, or 4, of whom 47 were administered G/P. All 47 patients (100%) achieved SVR12. No on-treatment virologic failures or relapses occurred. PK exposures of glecaprevir and pibrentasvir were comparable to exposures in adults. No adverse events (AEs) led to treatment discontinuation, and no serious AEs occurred. Conclusion: Adolescent patients with chronic HCV infection treated with G/P achieved a comparable exposure to adults, 100% SVR12 rate, and safety profile consistent with that in adults. This pangenotypic regimen demonstrated 100% efficacy within the adolescent population in as little as 8 weeks of treatment.

A Cost-Effectiveness Analysis of Glecaprevir/Pibrentasvir Versus Existing Direct-Acting Antivirals to Treat Chronic Hepatitis C in Japan.

INTRODUCTION: The objective of the study was to evaluate the cost-effectiveness of glecaprevir/pibrentasvir versus other direct-acting antivirals (DAAs) for treating chronic hepatitis C virus (HCV) infections in Japan. METHODS: We developed a health state transition model to capture the natural history of HCV. A cost-effectiveness analysis of DAAs from the perspective of a public healthcare payer in Japan with a lifetime horizon over annual cycles was performed. Treatment attributes, baseline demographics, transition probabilities, health-state utilities, and costs data were extracted from publications. Costs and outcomes were discounted at 2% per annum. In the base case we focused on genotype 1 (GT1) treatment-naïve patients without cirrhosis. The scenario analysis examined a pan-genotype treatment in GT1-3 (i.e., portfolio), treatment-naïve, and treatment-experienced patients. The portfolio cost-effectiveness of DAAs was derived by calculating a weighted average of patient segments defined by treatment history, cirrhosis status, and genotype. RESULTS: The base case results indicated that glecaprevir/pibrentasvir was dominant (i.e., generating higher quality-adjusted life years [QALYs] and lower lifetime costs) compared to all other DAAs. The predicted lifetime risk of hepatocellular carcinoma was 3.66% for glecaprevir/pibrentasvir and sofosbuvir/ledipasvir, 4.99% for elbasvir/grazoprevir, and 5.27% for daclatasvir/asunaprevir/beclabuvir. In scenario analysis the glecaprevir/pibrentasvir (GLE/PIB) portfolio dominated the sofosbuvir (SOF)-based portfolio (namely sofosbuvir/ledipasvir in GT1-2 and sofosbuvir + ribavirin in GT3). The base case probabilistic sensitivity analysis (PSA) showed that glecaprevir/pibrentasvir was cost-effective in 93.4% of the simulations for a willingness-to-pay/QALY range of Japanese yen (JPY) 1.6-20 million. The PSA for the portfolio scenario indicated that the GLE/PIB portfolio was cost-effective in 100% of simulations until the willingness-to-pay/QALY reached JPY 5.2 million; this proportion decreased to 69.4% at a willingness-to-pay/QALY of JPY 20 million. Results were also robust in deterministic sensitivity analyses. CONCLUSION: In GT1 treatment-naïve non-cirrhotic patients GLE/PIB was a cost-effective strategy compared to other DAAs. When a pan-genotypic framework was used, the GLE/PIB portfolio dominated the SOF-based portfolio.

Newly Diagnosed Hepatitis C in the US Commercially Insured Population Before and After the 2012 Implementation of Expanded Screening Guidelines.

BACKGROUND: In the United States in 2014, more than 3 million individuals were estimated to have chronic hepatitis C virus (HCV) infection, including many undiagnosed individuals. In 2012, the Centers for Disease Control and Prevention expanded its HCV testing recommendations to target all adults born between 1945 and 1965, in addition to at-risk individuals, which has led to an increase in newly diagnosed patients. Few studies have explored the medical cost or clinical status of patients who are newly diagnosed with HCV. OBJECTIVE: To compare the demographics, comorbidities, and medical costs of patients who are newly diagnosed and those who were previously diagnosed with HCV infection. METHOD: We conducted a retrospective study using 2013 claims data from the Truven Health MarketScan Commercial database to compare patients newly diagnosed with HCV infection in 2013 and patients who were diagnosed before 2013. The patients were divided into 2 cohorts based on the time of diagnosis before and after 2013. All patients were classified by disease stage and by comorbidities, and were required to have continuous health plan enrollment between January 2010 and December 2013. The full-year costs were tabulated for every patient, regardless of the date of diagnosis. RESULTS: Of the 9193 patients with an HCV diagnosis in 2013 in the database, approximately 26% (N = 2428) were newly diagnosed in 2013, of whom 12% (N = 299) had advanced-stage HCV. The average age of the newly diagnosed patients was 49.5 years versus 54.1 years for previously diagnosed patients. Patients who were previously diagnosed had a higher prevalence of HIV, diabetes, and more severe cancers than patients who were newly diagnosed with HCV. Patients who were newly diagnosed with HCV had a higher prevalence of acute liver failure and drug-induced psychosis. The average annual per-patient per-month (PPPM) medical costs for both groups was approximately $2200 in 2013. The annual medical cost for a patient who was newly diagnosed increased sharply in the year before diagnosis, from approximately $588 PPPM for the 3 years before the diagnosis to approximately $854 PPPM in the year before diagnosis. CONCLUSION: In 2013, the healthcare costs of patients who were newly diagnosed with HCV were similar in their first year of diagnosis to the costs of patients who had been diagnosed previously, although patients who were previously diagnosed had more advanced-stage disease. Patients who were newly diagnosed had 3-fold the healthcare costs in their first year of diagnosis versus the costs in the 3 years before their diagnosis.

Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV.

BACKGROUND & AIMS: Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. METHODS: Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV-, from a large de-identified insurance database from the USA. MEASUREMENTS: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17ß-estradiol were measured. RESULTS: Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771-26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090-0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV-, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130-2.794), premature birth (OR 1.34; 95% CI 1.060-1.690), gestational diabetes (OR 1.24; 95% CI 1.020-1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935-1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622-0.913). CONCLUSIONS: Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. LAY SUMMARY: Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

Prevalence and economic burden of extrahepatic manifestations of hepatitis C virus are underestimated but can be improved with therapy.

Despite guideline recommendations, access to hepatitis C virus (HCV) treatment is frequently restricted, with some payers approving therapy for only those with advanced disease or cirrhosis. However, delaying potentially curative treatment until the development of advanced liver disease may have costly consequences in terms of both hepatic complications and extrahepatic manifestations (EHMs) of HCV. Using a large claims database from the United States, we measured the risks and medical costs of 20 EHMs and investigated the role of treatment in different stages of liver fibrosis for mitigating the clinical and economic burden of these EHMs. After adjusting for potential confounders, including comorbid liver disease, patients with HCV had a significantly higher risk for any EHM (adjusted odds ratio, 2.23; P < 0.05) and higher EHM-related annual medical costs (adjusted medical cost difference, $6,458; P < 0.05) compared to matched patients without HCV. HCV treatment can offset the higher medical costs in patients with HCV by saving ∼$25,000 in all-cause medical costs per patient per year, with a large proportion attributable to savings in EHM-related medical costs (adjusted cost difference $12,773, P < 0.05). Finally, additional EHM-related medical costs could be saved by initiating HCV therapy in early stage fibrosis as opposed to late-stage fibrosis (adjusted medical cost difference, $10,409; P < 0.05). Conclusion: The clinical and economic burden of EHMs is substantial and can be reduced through viral eradication, especially if treatment is initiated early and not delayed until fibrosis advances. Considering that the wholesale acquisition cost of a 12-week course of therapy ranges from $55,000 to $147,000, the results of the current study suggest the cost of these treatments could be offset within 3 to 6 years by savings in all-cause medical costs. (Hepatology Communications 2017;1:439-452).

Geographic Variation in the Quality and Cost of Care for Patients with Rheumatoid Arthritis.

BACKGROUND: There is considerable push to improve value in health care by simultaneously increasing quality while lowering or containing costs. However, for diseases that are best treated with comparatively expensive treatments, such as rheumatoid arthritis (RA), there could be tension between these aims. In this study, we measured geographic variation in quality, access, and cost for patients with RA, a disease with effective but costly specialty treatments. OBJECTIVE: To assess the geographic differences in the quality, access, and cost of care for patients with RA. METHODS: Using large claims databases covering the period between 2008 and 2014, we measured quality of care metrics by metropolitan statistical areas (MSAs) for patients with RA. Quality measures included use of disease-modifying antirheumatic drugs (DMARDs) and tuberculosis (TB) screening before initiating biologic DMARD therapy. Access to care measures included measured detection and the share of patients with RA who visited a rheumatologist. Regression models were used to control for differences in patient demographics and health status across MSAs. RESULTS: For the 501,376 patients diagnosed with RA, in the average MSA 64.1% of RA patients received a DMARD, and 29.6% of RA patients initiating a biologic DMARD appropriately received a TB screening. Only 17% (73/430) of MSAs comprised the top 2 Medicare Advantage star ratings for DMARD use. Measured detection was 0.59% (IQR = 0.47%-0.71%; CV = 0.355) on average, and 57.6% (IQR = 48%-69%; CV = 0.341) of RA patients visited a rheumatologist. MSAs with the highest DMARD use spent $26,724 (in 2015 U.S. dollars) annually treating patients with RA, $5,428 more (P < 0.001) than low DMARD-use MSAs, largely because of higher pharmacy cost ($5,090 vs. $7,610, P < 0.001). However, MSAs with higher DMARD use had lower RA-related inpatient cost ($1,890 vs. $2,342, P = 0.024). CONCLUSIONS: There were significant geographic variations in the quality of care received by patients with RA, although quality was poor in most areas. Fewer than 1 in 5 MSAs could be considered high quality based on patient DMARD use. Access to specialist care may be an issue, since just over half of patients with RA visited a rheumatologist annually. Efforts to incentivize better quality of care holds promise in terms of unlocking value for patients, but for some diseases, this approach may result in higher costs. DISCLOSURES: The research reported in this manuscript was supported by AbbVie through consulting fees paid to Precision Health Economics (PHE). AbbVie and PHE collaborated to develop the study design and protocol. AbbVie and PHE participated in the interpretation of data, review, and approval of the manuscript. Shafrin and Shim are employed by PHE. Ganguli and Sanchez Gonzalez are employed by AbbVie. Seabury reports consulting fees from PHE. The results from this study were presented in poster form at the Academy of Managed Care Pharmacy's 2015 Annual Meeting and Expo; April 7-10, 2015; San Diego, California, and at the Academy of Managed Care Pharmacy's 2016 Annual Meeting and Expo; April 19-22, 2016; San Francisco, California. Study concept and design were contributed primarily by Shafrin, along with Ganguli and Seabury. Shafrin and Shim took the lead in data collection, and data interpretation was performed by Ganguli, Sanchez Gonzalez, Seabury, and Shafrin. The manuscript was written primarily by Shafrin, along with Shim and Seabury, and revised primarily by Ganguli, along with Sanchez Gonzalez and Seabury.

The wider public health value of HCV treatment accrued by liver transplant recipients.

OBJECTIVES: Organs for transplantation are scarce, but new medical therapies can prevent organ failure and the need for transplants. We sought to describe the unique value created by treatments that spare organs from failure and thus conserve donated organs for transplant into others, using hepatitis C virus (HCV) as a case study. STUDY DESIGN: Epidemiologic-economic model. METHODS: Using data on trends in chronic liver disease, liver disease progression, and liver transplant allocation models, as well as the effectiveness of new HCV treatments, we estimate the potential effects of systematic HCV screening and treatment on the demand for liver transplants in the United States. We estimate the spillover benefits to patients with all-cause liver disease in terms of increased availability of transplants and life-years gained. RESULTS: We estimated that systematic HCV screening and treatment could spare 10,490 liver transplants to HCV-infected patients from 2015 to 2035. An estimated 7321 transplants would accrue to patients with end-stage liver disease without HCV and 3169 transplants to those with uncured HCV, providing approximately 52,700 and 22,800 additional life-years, respectively. CONCLUSIONS: Treatment advances for HCV have the potential to generate considerable spillover benefits to patients awaiting transplants for non-HCV-mediated liver failure. For other diseases in which organ transplants are in short supply, our study provides a novel pathway by which positive spillovers may accrue from treatments that prevent end-stage organ disease.

Value of expanding HCV screening and treatment policies in the United States.

OBJECTIVES: To investigate the value of expanding screening and treatment for hepatitis C virus (HCV) infection in the United States. STUDY DESIGN: Discrete-time Markov model. METHODS: We modeled HCV progression and transmission to analyze the costs and benefits of investment in screening and treatment over a 20-year time horizon. Population-level parameters were estimated using National Health and Nutrition Examination Survey data and published literature. We considered 3 screening scenarios that vary in terms of clinical guidelines and physician awareness of guidelines. For each screening scenario, we modeled 3 approaches to treatment, varying the fibrosis stage of treatment initiation. Net social value was the key model outcome, calculated as the value of benefits from improved quality-adjusted survival and reduced transmission minus screening, treatment, and medical costs. RESULTS: Expanded screening policies generated the largest value to society. However, this value is constrained by the availability of treatment to diagnosed patients. Screening all individuals in the population generates $0.68 billion in social value if diagnosed patients are treated in fibrosis stages F3-F4 compared with $824 billion if all diagnosed patients in stages F0-F4 are treated. Moreover, increased screening generates cumulative net social value by year 8 to 9 under expanded treatment policies compared with 20 years if only patients in stages F3-F4 are treated. CONCLUSIONS: Although increasing screening for HCV may generate some value to society, only when paired with expanded access to treatment at earlier disease stages will it produce considerable value. Such a "test and treat" strategy is likely to entail higher short-term costs but also yield the greatest social benefits.

Costs and spillover effects of private insurers' coverage of hepatitis C treatment.

OBJECTIVES: Hepatitis C virus (HCV) treatment incentives for private payers may be misaligned because payers must bear immediate costs and may not realize long-term benefits. However, these benefits may accrue to future payers, including Medicare. We examined how and to what extent private payers' current HCV treatment coverage decisions impact Medicare's and private payers' future costs. STUDY DESIGN: Discrete-time Markov model. METHODS: We modeled HCV disease progression and transmission to simulate the economic and social effects of different private-payer HCV treatment scenarios on Medicare. The model examined differences between a baseline scenario (current practice guidelines) and 2 alternative scenarios that expand treatment coverage. Spillover effects were measured as reduced HCV treatment costs and medical expenditures in Medicare. We calculated the spillover effects and net social value of each scenario (total value of quality-adjusted life-years accrued over time minus cumulative treatment and medical costs). RESULTS: With expanded HCV treatment coverage, private payers experience reduced medical expenditures in the 3-to-5-year time horizon; however, they still face higher treatment costs. Over a 20-year horizon, private payers experience overall savings of $10 billion to $14 billion after treatment costs. The expansion of coverage by private payers generates positive spillover benefits to Medicare of $0.3 billion to $0.7 billion over a 5-year horizon, and $4 billion to $11 billion over a 20-year horizon. CONCLUSIONS: When private payers increase HCV treatment coverage, they may achieve significant savings while inducing spillover benefits to Medicare. Future savings, however, may not motivate immediate treatment investments among private payers who experience high beneficiary turnover.

Cost-Effectiveness of Genotype 1 Chronic Hepatitis C Virus Treatments in Patients Coinfected with Human Immunodeficiency Virus in the United States.

INTRODUCTION: New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients. METHODS: A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R. CONCLUSION: In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV.