One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11 years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

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.

Estimating the response and economic burden of rheumatoid arthritis patients treated with biologic disease-modifying antirheumatic drugs in Taiwan using the National Health Insurance Research Database (NHIRD).

BACKGROUND: Previous studies in Taiwan utilizing the Taiwan's National Health Insurance Database (NHIRD) have estimated the direct healthcare costs of RA patients, but they have not focused on patients on bDMARDs, or considered patients' response to therapy. OBJECTIVES: The objective of this study was to estimate the rate of inadequate response for patients newly treated with biologic disease-modifying antirheumatic drugs (bDMARDs) as well as their costs and resource use. METHODS: Data were from the catastrophic illness file within the NHIRD from 1/1/2009 to 12/31/2013. Patients with RA, which was categorized by the presence of a catastrophic illness card, that were previously bDMARD-naïve, were included in this study if they initiated their first bDMARD during the index period. The index period included all of 2010, a pre-index period consisting of the index date- 365 days, and a follow-up period including the index date to 365 days post-index, were also included. Previously biologically-naïve patients were indexed into the study on the date of their first claim for a bDMARD. A validated algorithm was used to examine the rate of inadequate response (IR) in the biologically-naïve cohort of patients. Inadequate responders met one or more of the following criteria during their year of follow-up: low adherence (proportion of days covered <0.80); switched to or added a second bDMARD; added a new conventional synthetic DMARD (csDMARD); received ≥1 glucocorticoid injection; or increased oral glucocorticoid dosing. All-cause mean annual direct costs and resource use were measured in the year of follow-up. Costs were converted from NT$ to USD using 1 NT$ = 0.033 USD. RESULTS: A total of 818 patients with RA initiated their first bDMARD (54% etanercept and 46% adalimumab) in 2010. After one year of follow-up, 32% (n = 258) were classified as stable, 66% (n = 540) had an IR, and 2% (n = 20) were lost to follow-up. During the follow-up period mean annual total direct costs were $16,136 for stable patients compared to $14,154 for patients with IR. Mean annual non-medication direct costs were $937 for stable patients and $1,574 for patients with IR. Mean annual hospitalizations were higher for patients with IR (0.46) compared to stable patients (0.10) during the one year follow-up period. CONCLUSIONS: The majority of patients that were previously naïve to bDMARDs had an IR to their first bDMARD during the year of follow-up. Patients with an IR had numerically increased all-cause resource utilization and non-medication costs during the follow-up period compared to patients with stable disease. This level of IR suggests an unmet need in the RA treatment paradigm.

Ixekizumab for Treating Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence invited Eli Lilly and Company Ltd, the company manufacturing ixekizumab (tradename Taltz®), to submit evidence for the clinical and cost effectiveness of ixekizumab. Ixekizumab was compared with tumour necrosis factor-α inhibitors (etanercept, infliximab, adalimumab), ustekinumab, secukinumab, best supportive care and, if non-biological treatment or phototherapy is suitable, also compared with systemic non-biological therapies and phototherapy with ultraviolet B radiation for adults with moderate-to-severe plaque psoriasis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group. This article presents a summary of the company submission, the Evidence Review Group report and the development of the National Institute for Health and Care Excellence guidance for the use of this drug in England and Wales by the Appraisal Committee. The Evidence Review Group produced a critical review of the clinical and cost effectiveness of ixekizumab based on the company submission. The company submission presented three randomised controlled trials identified in a systematic review. All randomised controlled trials were phase III, multicentre placebo-controlled trials including 3866 participants with moderate-to-severe psoriasis. Two trials also included an active comparator (etanercept). All randomised controlled trials showed statistically significant increases in two primary outcomes, static Physician Global Assessment (0,1) and improvement of 75% from baseline in the Psoriasis Area and Severity Index. Ixekizumab was generally well tolerated in the randomised controlled trials, with similar discontinuation rates because of adverse events as placebo or etanercept. The most frequent adverse events of special interest were infections and injection-site reactions. The company submission also included a network meta-analysis of relevant comparators. The Evidence Review Group highlighted some issues regarding the systematic review process and an issue with the generalisability of the findings in that the trials failed to include patients with moderate psoriasis according to a widely used definition. This issue was considered by the Appraisal Committee and the population was deemed generalisable to patients in England and Wales. Based on the network meta-analysis, the Appraisal Committee concluded that ixekizumab was more clinically effective than adalimumab and ustekinumab, and agreed it was likely that ixekizumab was similarly effective compared with secukinumab and infliximab while tolerability was similar to other biological treatments approved for treating psoriasis. The Evidence Review Group's critical assessment of the company's economic evaluation highlighted a number of concerns, including (1) the use of relative outcomes such as Psoriasis Area and Severity Index response to model the cost effectiveness; (2) the exclusion of the consequences of adverse events; (3) the assumption of no utility gain in the induction phase; (4) equal annual discontinuation rates for all treatments; (5) the selection of treatment sequences for consideration in the analyses and; (6) the transparency of the Visual Basic for Applications code used to develop the model. Although some of these issues were adjusted in the Evidence Review Group base case, the Evidence Review Group could not estimate the impact of all of these issues, and thus acknowledges that there are still uncertainties concerning the cost-effectiveness evidence. In the Evidence Review Group base-case incremental analysis, the treatment sequence incorporating ixekizumab in the second line has an incremental cost-effectiveness ratio of £25,532 per quality-adjusted life-year gained vs. the etanercept sequence. Ixekizumab in the first-line sequence has an incremental cost-effectiveness ratio of £39,129 per quality-adjusted life-year gained compared with the treatment sequence incorporating ixekizumab in the second line. Consistent with its conclusion regarding clinical effectiveness, the Appraisal Committee concluded that the cost effectiveness of ixekizumab for treating moderate-to-severe plaque psoriasis was similar to that of other biological treatments, already recommended in previous National Institute for Health and Care Excellence guidance. The committee concluded that the incremental cost-effectiveness ratio was within the range that could be considered a cost-effective use of National Health Service resources.

Secukinumab is the most efficient treatment for achieving clear skin in psoriatic patients: a cost-consequence study from the Spanish National Health Service.

OBJECTIVE: To compare the cost consequence of biologic drugs for moderate-to-severe psoriasis from the perspective of the Spanish National Health System. METHODS: We built a decision tree with a two-year time horizon. Efficacy data for biologics (etanercept, infliximab, adalimumab, ustekinumab and secukinumab) were drawn from published meta-analyses: PASI75 for the induction phase and PASI90 for the rest of follow-up. Patients with PASI < 75 at week 10-16 were switched to another biologic agent. Efficacy at week 24 was considered the highest possible efficacy for each drug and assumed to remain constant throughout the two-year period. Only drug treatment costs were used. The number needed to treat (NNT), annual cost per patient, annual cost per patient with PASI90 (cost per responder) and cost of primary failure (PASI < 75 at first efficacy evaluation) were calculated. RESULTS: Secukinumab monotherapy was associated with the lowest cost per responder, followed by infliximab and ustekinumab. Treatment sequences starting with secukinumab were the most efficient, having the lowest NNT and cost per responder. Although the annual cost per treatment is similar for all drugs, there are huge differences in the cost per responder. CONCLUSIONS: Secukinumab as first-line biologic treatment is the most efficient treatment for moderate-to-severe plaque psoriasis in the short-to-medium term.

Cost-utility analysis of certolizumab pegol in combination with methotrexate in patients with moderate-to-severe active rheumatoid arthritis in Greece.

We aimed to evaluate the cost-effectiveness of certolizumab pegol (CZP), a pegylated fc-free anti-TNF, as add-on therapy to methotrexate (MTX) versus etanercept, adalimumab, or golimumab in patients with moderate-to-severe active rheumatoid arthritis (RA) not responding to the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). A Markov model (6-month cycle length) assessed health and cost outcomes of CZP versus other anti-TNFs recommended for RA in Greece over a patient's lifetime. Following discontinuation of first-line anti-TNF, patients switched to second anti-TNF and then to a biologic with another mode of action. Sequential use of csDMARDs followed third biologic. Clinical data and utilities were extracted from published literature. Analysis was conducted from third-party payer perspective in Greece. Costs (drug acquisition, administration, monitoring, and patient management) were considered for 2014. Results presented are incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY). Probabilistic sensitivity analysis (PSA) ascertained robustness of base-case findings. Base-case analysis indicated that CZP+MTX was more costly and more effective compared with Etanercept+MTX (base-case ICER: €3,177 per QALY), whilst versus adalimumab/golimumab, CZP was dominant (less costly, more effective). For all comparisons, CZP treatment resulted in greater improvements in life expectancy and QALYs. PSA indicated that at the willingness-to-pay threshold of €34,000/QALY, CZP+MTX was associated with a 71.6, 97.9, or 99.2% probability of being cost-effective versus etanercept, golimumab, or adalimumab, respectively, in combination with MTX. This analysis demonstrates CZP+MTX to be a cost-effective alternative over Etanercept+MTX and a dominant option over Adalimumab+MTX and Golimumab+MTX for management of RA in Greece.

[Cost Effectiveness of Treatments of Psoriasis with a PASI 75 and one Period of 12 Weeks]. / Coste efectividad de diferentes tratamiento para la psoriasis.

OBJECTIVE: The objective was to evaluate the efficiency (relation between the cost and the results in health) of the treatments in psoriasis, seeking a higher quality of economic evaluations, consistency and transparency in these studies. METHODS: We developed a model of economic evaluation in psoriasis collecting all the many direct and indirect costs of each treatment. The effectiveness indicator used was Psoriasis Area Severity Index [PASI 75] which is generally acceptable in studies of psoriasis. The effectiveness indicator was a PASI 75.Subsequently we calculated the Incremental Cost-Effectiveness Ratio (ICER) for the period of 12 weeks and PASI 75, ordering treatments by level of effectiveness at the expense of treatment costs. RESULTS: The most cost effective treatment was methotrexate (ICER -7.5) followed by acitretin (ICER 29.5). The least cost has proved effective PUVA (ICER 4,651), followed by UVB narrow band (2,886.1). CONCLUSIONS: when taking into account both direct and indirect costs together with efficiency, methotrexate is the most cost effective treatment.

OBJETIVO: Los nuevos tratamientos biológicos, si bien mejoran la calidad de vida del paciente, incrementan los costes exponencialmente en relación al resto de tratamientos. El objetivo fue calcular el tratamiento más coste efectivo de los existentes para la psoriasis. METODOS: Se desarrolló un modelo de evaluación económica en psoriasis recogiendo todos los costes directos e indirectos de cada tratamiento. El indicador de efectividad que se utilizó fue Psoriasis Area Severity Index (PASI 75), que es el aceptable de manera general en estudios de psoriasis. Posteriormente se realizó un análisis de incremento coste efectividad (ICER) para el periodo de 12 semanas y PASI 75, ordenando los tratamientos por nivel de efectividad en detrimento de los costes de los tratamientos. RESULTADOS: El tratamiento más coste efectivo fue el metotrexato (ICER -7,5) seguido de acitretina (ICER 29,5). El menos coste efectivo resultó ser PUVA (ICER 4.651) seguido de UVB de banda estrecha (2.886,1). CONCLUSIONES: Aunque el tratamiento más económico teniendo en cuenta solo los costes directos sería el UVBbe, al tener en cuenta los costes indirectos y ajustarlos por la efectividad, el tratamiento más coste efectivo es el metotexato.

Economic Burden of Switching to a Non-Tumor Necrosis Factor Inhibitor Versus a Tumor Necrosis Factor Inhibitor Biologic Therapy among Patients with Rheumatoid Arthritis.

INTRODUCTION: The objective of this study was to examine healthcare resource utilization (HRU) and costs associated with switching to another tumor necrosis factor alpha inhibitor (TNFi) therapy versus a non-TNFi therapy among patients with rheumatoid arthritis (RA) discontinuing use of an initial TNFi biologic therapy. METHODS: Patients with ≥2 RA diagnoses who used ≥1 TNFi on or after their initial RA diagnosis were identified in a US employer-based insurance claims database. Patients were selected based on ≥1 claim of another TNFi or a non-TNFi biologic therapy (occurring after 2010, and within 30 days before to 60 days after discontinuation of the initial TNFi), and continuous insurance ≥6 months before (baseline period) and ≥12 months after the switch date (study period). Patient demographic and clinical characteristics were measured during the baseline period. All-cause and RA-related HRU and costs were analyzed during the 12-month study period using multivariable regression analysis controlling for baseline characteristics and selected comorbidities. RESULTS: Of the 1577 patients with RA that switched therapies, 1169 patients used another TNFi and 408 patients used a non-TNFi biologic. The most commonly used initial TNFi treatments were etanercept (50%) and adalimumab (34%) among the TNFi cohort, and infliximab (39%) and etanercept (28%) among the non-TNFi cohort. The TNFi cohort had significantly fewer outpatient visits [all-cause: 23.01 vs. 29.77 visits/patient/year; adjusted incidence rate ratio (IRR) = 0.78, P < 0.001; RA-related: 7.42 vs. 13.58; adjusted IRR = 0.58, P < 0.001] and rheumatologist visits (all-cause: 4.01 vs. 6.81; adjusted IRR = 0.66, P < 0.001; RA-related: 3.23 vs. 6.40; adjusted IRR = 0.58, P < 0.001) than the non-TNFi cohort. All-cause total costs were significantly lower for patients who switched to another TNFi instead of a non-TNFi therapy ($36,932 vs. $44,566; adjusted difference = $7045, P < 0.01), as were total RA-related costs ($26,973 vs. $31,735; adjusted difference = $4904, P < 0.01). CONCLUSION: Adult patients with RA discontinuing TNFi therapy who switched to an alternative TNFi incurred lower healthcare costs than patients who switched to a non-TNFi biologic. FUNDING: AbbVie, Inc.

Efficacy and cost of etanercept in long-term psoriasis: Rational use in clinical practice.

INTRODUCTION: The advent of the biological therapies has led health expenditure in dermatology units. This study aims to evaluate, in our regular clinical practice, the patterns of use of etanercept and its influence on efficacy and safety outcomes, as well as the real costs associated with continuous and intermittent treatment regimens. METHODS: Observational, retrospective, non-interventionist, and multicenter study to analyze the experience of the treatment with etanercept in the management of moderate-to-severe plaque psoriasis, given according to the daily clinical practice of the Dermatology Departments of the Complejo Hospitalario de Jaén and the Hospital Universitario Virgen del Rocío (Seville). RESULTS: 83.3% (n = 45) of the 54 patients included in our study received the continuous regimen of Etanercept, whereas 16.7% (n = 9) were given the intermittent regimen. 94.4% (n = 51) of the patients studied began the Etanercept treatment at a dose of 50 mg/week. The mean patient/year cost of the study population is €11 298.80 (95%CI €10 551.40-€12 046.20). Breaking down the first and the second year of treatment by regimen, in the continuous regimen the mean cost would be €12 294.15 and €12 327.05 in the first and the second year, respectively, and €10 302.07 and €4986.51 in the intermittent regimen. DISCUSSION: Etanercept is a biologic that had demonstrated its versatility over the years and permits the individualization of treatment in our patients, thus having a direct impact on drug-related costs. This is well demonstrated in our series, where 94.4% of our patients begin with the dose of 50 mg/d. Our study yields relatively higher figures in patients on continuous therapy, with 77.1% of them maintaining PASI75 at week 24. CONCLUSIONS: We present our experience in regular clinical practice with etanercept, showing it to be an effective, safe, and versatile drug that permits patient-tailored treatment, delivering a frankly satisfactory control of our psoriasis patients.

Efficiency of biological therapies in patients with moderate to severe psoriasis: impact of a pharmacotherapeutic protocol.

BACKGROUND: It is not clear how to best use biologics in the treatment of psoriasis. Our objective was to assess use of a protocol for biological therapies (BT) in psoriasis. METHODS: A consensus protocol was established that included the indications for BT and dose optimization. Patient's characteristics, effectiveness, and cost of BT were analyzed before and after the implementation with two cross-sectional studies to assess its impact. RESULTS: About 106 were treated before the protocol and 118 patients were treated after. After implementing the protocol, the dose was reduced in 43.4% of the patients receiving adalimumab, in 37.5% for etanercept, in 28.6% for infliximab, and in 14.7% for ustekinumab. No statistically significant differences were found in PASI score after the implementation of the protocol, except for the percentage of patients that achieved PASI 75 with ustekinumab, which was slightly higher. The global yearly savings achieved with the protocol implementation were 115,969 €. CONCLUSIONS: The protocol helped to increase the efficiency of BT, with decreasing doses of BT without affecting treatment effectiveness.

Clinical and economic review of secukinumab for moderate-to-severe plaque psoriasis.

Secukinumab represents the first IL-17A antagonist among the available biologic therapies approved for moderate-to-severe plaque psoriasis management. Secukinumab demonstrated greater efficacy over placebo, etanercept and ustekinumab in patients that had limited benefit from non-biologic systemic therapies and phototherapy. Despite standard-of-care systemic therapies being more likely to be cost-effective at this time, a Canadian cost-utility analysis found secukinumab to display benefit in quality-of-life gains in moderate-to-severe plaque psoriasis patients, and greater cost-effectiveness when compared to other biologic systemic therapies. Determination of the true economic value of secukinumab amongst the available therapies for moderate-to-severe plaque psoriasis will require continued economic evaluation.

Dose Modification in Biologic Therapy for Moderate to Severe Psoriasis: A Descriptive Analysis in a Clinical Practice Setting.

INTRODUCTION: In biologic therapy, dose modification in carefully selected patients when psoriasis is in remission could reduce treatment costs and the risks associated with drug exposure. MATERIAL AND METHODS: Observational, descriptive, crosssectional study, performed in January 2014, of 112 patients with moderate to severe psoriasis who had been on biologic therapy for at least 6 months. The therapeutic objective in all cases was to achieve and maintain a 75% reduction in Psoriasis Area and Severity Index (PASI 75). All the patients had started treatment with the standard regimen. During treatment, the dose had been reduced in patients who achieved the therapeutic objective and escalated in those who failed to respond adequately to standard doses. RESULTS: At the time of the study, 42.9% of the patients were receiving the standard dose, 50% were on a reduced dose, and 7.1% were on an escalated regimen. The agent with which the dose was most often reduced was adalimumab (57.7%), and the agents with which therapy was most often escalated were ustekinumab (17.9%) and infliximab (12.5%). Patients who received reduced doses had significantly longer-standing disease (P=.049) and longer treatment duration with the same biologic agent (P=.009). In the group that did not fulfill the criteria for dose reduction, the proportion of patients with psoriatic arthritis was significantly higher (P=.023). Cost savings were as follows: 21.5% with adalimumab, 13.8% with etanercept, .9% with ustekinumab, and .55% with infliximab. CONCLUSIONS: Patients with longer-standing disease and longer treatment duration with the same biologic agent were significantly more likely to be candidates for dose reduction. The proportion of patients with psoriatic arthritis was greater in the group of patients who did not fulfill the conditions for dose reduction. The overall cost saving achieved using the dose modification algorithm described in this study was 13%. Controlled studies are needed to define the profile of the patients best suited for dose reduction strategies without loss of treatment efficacy.