Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.

Secukinumab significantly reduces psoriasis-related work impairment and indirect costs compared with ustekinumab and etanercept in the United Kingdom.

BACKGROUND: Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown. OBJECTIVE: To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK). METHODS: This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (i) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (ii) weekly/annual work productivity loss by PASI response level; (iii) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (iv) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different time points and with patient cohorts, including FIXTURE. RESULTS: In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI < 50: 22.8%/7.60 h; PASI 50-74: 13.3%/4.45 h; PASI 75-89: 6.4%/2.14 h; PASI ≥ 90: 4.9%/1.65 h. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P = 0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρ<0.0001). Average annual indirect cost savings with secukinumab were £355 vs. ustekinumab and £1061 versus etanercept. Results at 52 weeks were similar. CONCLUSIONS: Secukinumab significantly reduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the United Kingdom.

Factor VIII alloantibody inhibitors: cost analysis of immune tolerance induction vs. prophylaxis and on-demand with bypass treatment.

Development of inhibitors (alloantibodies to exogenous factor VIII) is the most significant treatment complication in patients with haemophilia A. The only proven way to eradicate inhibitors is through immune tolerance induction (ITI), while bypassing agents are typically employed to treat or prevent bleeds in patients with high titre inhibitors. Costs of these approaches have not been well studied. The aim of this study was to compare lifetime costs of treating patients with severe haemophilia A with inhibitors using on-demand or prophylaxis treatment with bypassing agents and ITI. A decision-analytic model was developed to compare the treatment costs and outcomes. Quantitation of the reduction in bleeding events for patients on prophylaxis and after eradication of inhibitors when on ITI and relapse of inhibitors was derived from published studies. Costs were obtained from standard US costing sources and are reported in 2014 US dollars. Costs and outcomes were discounted 3% per annum. Lifetime costs of treating patients with inhibitors are lower for ITI vs. on-demand or prophylaxis. Patients are also projected to live longer, have greater quality-adjusted life-years, and have fewer bleeding events than patients treated on-demand. Treating patients via ITI to eradicate inhibitors may result in lower lifetime costs and greater life-years and quality-adjusted life-years than treating with bypassing agents.

Cost-effectiveness of bisphosphonate therapies for women with postmenopausal osteoporosis: implications of improved persistence with less frequently administered oral bisphosphonates.

OBJECTIVE: Studies have shown that weekly bisphosphonate dosing results in improved persistence compared to daily dosing among patients with postmenopausal osteoporosis, yet more than 50% of patients discontinue therapy within a year. An oral, less frequent administration bisphosphonate provides an opportunity to improve persistence, a parameter not well modeled in previous cost-effectiveness analyses of osteoporosis therapies. RESEARCH DESIGN AND METHODS: We developed a Markov model to estimate the effect of improved persistence on the cost-effectiveness of bisphosphonates among postmenopausal women with established osteoporosis (vertebral fracture and bone mineral density T-score

Inhibition of cell migration and angiogenesis by the amino-terminal fragment of 24kD basic fibroblast growth factor.

The 24-kDa form of basic fibroblast growth factor inhibits the migration of endothelial cells and mammary carcinoma cells while continuing to promote cell proliferation. This molecule consists of the 18-kDa fibroblast growth factor sequence plus an additional 55 amino acids at the amino-terminal end. Antibody neutralization studies suggested that the inhibition of migration is associated with these 55 amino acids, whereas the promotion of proliferation localizes to the 18-kDa domain. To determine whether 24kD basic fibroblast growth factor could be modified to eliminate its effect on cell proliferation but retain its inhibition of migration, portions of the carboxyl-terminal end of 24kD fibroblast growth factor were deleted, and the products were tested on MCF-7 and endothelial cells. A protein consisting of the 55 amino acids of the amino-terminal end and the first 31 amino acids of 18kD basic fibroblast growth factor (ATE+31) inhibited migration by 80% but did not promote cell growth. Arginine to alanine substitutions within the first 21 amino acids of the carboxyl-terminal end substantially reduced the efficacy of ATE+31, whereas substitutions in the remaining part of the molecule had no effect. Competition binding experiments showed that ATE+31 does not compete with 24kD basic fibroblast growth factor for binding to fibroblast growth factor receptor 1. In an in vivo matrigel plug assay, 150 nm ATE+31 peptide reduced angiogenesis by 80%. These studies demonstrate that the amino-terminal end of 24kD basic fibroblast growth factor is responsible for an activity that inhibits the migration rates of cultured cells as well as the angiogenic response in vivo.