Real-world use of extracorporeal photopheresis for patients with cutaneous T-cell lymphoma in the United States: 2010-2015.

Introduction: The National Comprehensive Cancer Network and the European Organization for Research and Treatment of Cancer recommend extracorporeal photopheresis (ECP) as systemic therapy for cutaneous T-cell lymphoma (CTCL).Objective: To investigate real-world use of ECP in CTCL patients in the US.Methods: Data from the Truven MarketScan® database (2010-2015) were used to create a cohort of CTCL patients receiving systemic treatment. Multivariable regressions were performed to compare health care resource utilization between ECP and propensity score-matched non-ECP patients.Results: Of the 1106 eligible patients, 117 (10.6%) received ECP, with an average treatment duration of 13.6 months. Psoriasis, organ transplant, graft versus host disease, and scleroderma were the most common comorbidities. ECP was used as monotherapy in 76 patients (65.0%) and combination in 41 patients (35.0%), mostly with interferon and/or a retinoid. Higher Charlson Comorbidity Index (2.6 vs 2.2, p < .05), rates of organ transplant (49.6% vs 7.8%, p < .001), and graft vs host disease (41.9% vs 3.4%, p < .001) were observed in ECP versus non-ECP patients. Post-matching analyses showed that ECP patients had shorter all-cause inpatient stay (6.67 vs 11.80 days, p = .001).Conclusions: Approximately 1 out of 10 CTCL patients receiving systemic treatment were on ECP treatment in the US. Post-matching analysis showed ECP was associated with a shorter hospital stay.

Randomized controlled study of ECP with methoxsalen as first-line treatment of patients with moderate to severe cGVHD.

The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT). Other outcomes included quality of life (QoL) measures and safety. Sixty patients were randomized; ITT included 53 patients (SoC+ECP: 29; SoC: 24). Week 28 ORR was 74.1% (SoC+ECP) and 60.9% (SoC). Investigator-assessed ORR was 56.0% (SoC+ECP) and 66.7% (SoC). Patients treated with SoC experienced a decline in QoL over the 28-week study period; QoL remained unchanged in SoC+ECP patients. Most frequent treatment-emergent adverse events (TEAEs) in SoC+ECP patients were hypertension (31.0%), cough (20.7%), dyspnea (17.2%), and fatigue (17.2%). Seventeen patients (SoC+ECP: 8; SoC: 9) experienced 35 serious adverse events (SAEs). No TEAEs or SAEs were considered related to the ECP instrument or methoxsalen. The encouraging short-term results of this study could inform the design of subsequent studies. This trial was registered at www.clinicaltrials.gov as #NCT01380535.

The Budget Impact of Increased Use of Febuxostat in the Management of Gout: A US Health Plan Managed Care Pharmacy and Medical Costs Perspective.

PURPOSE: Gout is a chronic disease characterized by the deposition of urate crystals in the joints and throughout the body, caused by an excess burden of serum uric acid (sUA). The study estimates pharmacy and medical cost budgetary impacts of wider adoption by US payers of febuxostat, a urate-lowering therapy (ULT) for the treatment of gout. METHODS: A US payer-perspective budget impact model followed ULT patients from a 1,000,000-member plan over 3 years. The current market share scenario, febuxostat (6%) and ULT allopurinol (94%), was compared with an 18% febuxostat market share. Data were implemented from randomized controlled trials, census and epidemiologic studies, and real-world database analyses. An innovation was the inclusion of gout-related chronic kidney disease costs. Cost results were estimated as annual and cumulative incremental costs, expressed as total costs, cost per member per month, and cost per treated member per month. Clinical results were also estimated. FINDINGS: Increasing the febuxostat market share resulted in a 6.3% increase in patients achieving the sUA target level of <6.0 mg/dL and a 1.4% reduction in gout flares during the 3-year period. Total cost increased 1.4%, with a 49.9% increase in ULT costs, a 1.4% reduction in flare costs, a 1.2% reduction in chronic kidney disease costs, and a 2.8% reduction in gout care costs. The cumulative incremental costs were $1,307,425 in the first year, $1,939,016 through the second year, and $2,092,744 through the third year. By the third year, savings in medical costs offset most of the increase in treatment costs. Impacts on cumulative cost per member per month and cumulative cost per treated member per month followed the same pattern, with the highest impact in the first year and cumulative impacts declining during the 3-year period. The cumulative cost per member per month impact was estimated as $0.109, $0.081, and $0.058 and the cumulative cost per treated member per month impact was estimated as $12.416, $9.207, and $6.625 in the first year, through the second year, and through the third year, respectively. IMPLICATIONS: Expanding the febuxostat market share would result in improved clinical outcomes, but with an overall increase in costs over 3 years due to higher costs of treatment. By the third year, savings in medical costs, primarily in chronic kidney disease costs, would offset most of the increase in treatment costs. Expanded use of febuxostat in the treatment of all gout patients, independent of renal impairment status, should be considered based on improved clinical outcomes and longer-term medical cost savings associated with these improved outcomes.

Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies. OBJECTIVE: To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD. METHODS: A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings. RESULTS: Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. CONCLUSIONS: Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. DISCLOSURES: No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

Febuxostat in the management of gout: a cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout. METHODS: A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40-80 mg and allopurinol 100-300 mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided. RESULTS: Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures. CONCLUSIONS: Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.

A comparison between anti-Th/To- and anticentromere antibody-positive systemic sclerosis patients with limited cutaneous involvement.

OBJECTIVE: To compare anti-Th/To-positive and anticentromere antibody (ACA)-positive patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: We reviewed the medical records of 107 anti-Th/To-positive patients and 365 ACA-positive patients who were first evaluated during 1985-2000. ACA was detected by indirect immunofluorescence on HEp-2 cell substrate, and anti-Th/To was detected by RNA immunoprecipitation with K562 cell extracts. Patients were included if they had a clinical diagnosis of lcSSc, and excluded if they had >1 SSc-associated serum autoantibody. RESULTS: The final study groups comprised 87 lcSSc patients with anti-Th/To antibodies and 306 with ACAs. Anti-Th/To-positive patients were younger (P < 0.04) and had a shorter disease duration at their first evaluation (P < 0.003). Patients with anti-Th/To antibodies had more subtle skin changes, less severe vascular involvement, and less frequent distal esophageal hypomotility. Both groups had a higher frequency of "intrinsic" pulmonary hypertension than has been previously reported in the literature (28% and 19% of anti-Th/To-positive and ACA-positive patients, respectively), perhaps due to referral bias. Patients in the anti-Th/To group more often had radiographic evidence of interstitial lung disease (48% versus 13% of the ACA group; P < 0.0001). Scleroderma renal crisis was uncommon (4 cases), but occurred exclusively in the anti-Th/To group. Survival among the anti-Th/To-positive patients was reduced compared with that in the ACA group (P < 0.02). CONCLUSION: Patients with anti-Th/To and those with ACA most often develop lcSSc and have a high frequency of "intrinsic" pulmonary hypertension. Compared with the ACA patients, anti-Th/To lcSSc patients have more subtle cutaneous, vascular, and gastrointestinal involvement, but more often have certain features typically seen in diffuse scleroderma, such as pulmonary fibrosis and scleroderma renal crisis, as well as reduced survival.