Real-World Experience With Apremilast in the Treatment of Adults With Moderate to Severe Plaque Psoriasis in Québec: A Claims-Based Analysis of Drug Utilization and Healthcare Resource Utilization.

BACKGROUND: In Québec, targeted biologic therapies for moderate to severe plaque psoriasis are restricted to patients who have not responded to phototherapy or conventional systemic treatment, primarily due to high drug costs. Apremilast, an oral treatment for plaque psoriasis, was added to the Québec provincial health insurance plan (Régie de l'assurance maladie du Québec; RAMQ) formulary in 2015, making this the only province in Canada with public drug plan reimbursement for apremilast. OBJECTIVES: The aim of this study is to describe patients' characteristics, treatment patterns, healthcare resource utilization (HCRU), and associated costs and to measure real-world budget impact of using apremilast before biologics in plaque psoriasis. METHODS: This study was performed using RAMQ drug claims and medical services data. Patients diagnosed with psoriasis between January 2015 and December 2017 were identified. Medical services and prescription claims were categorized as all-cause and psoriasis-related. Using RAMQ database estimates, a 3-year budget impact analysis was developed comparing treatment cost with and without the addition of apremilast to the formulary. RESULTS: In all, 540 patients were identified (apremilast: n = 92; biologics: n = 448). Comorbidity burden and treatment persistence and adherence were comparable between apremilast and biologic users. The year following the index date, all-cause HCRU was lower for apremilast versus biologic users (CAN$19 763 vs CAN$28 025; P < .01), mainly driven by drug cost. Using apremilast before biologics resulted in an estimated RAMQ net savings of CAN$49 290 (2015), CAN$746 856 (2016), and CAN$1 216 512 (2017), and a total savings of CAN$2 012 658 since apremilast's addition to the formulary. CONCLUSION: Adding apremilast to the drug formulary of other Canadian provinces could result in significant healthcare savings.

Economic impact of potentially inappropriate prescribing and related adverse events in older people: a cost-utility analysis using Markov models.

OBJECTIVES: To determine the economic impact of three drugs commonly involved in potentially inappropriate prescribing (PIP) in adults aged ≥65 years, including their adverse effects (AEs): long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines and proton pump inhibitors (PPIs) at maximal dose; to assess cost-effectiveness of potential interventions to reduce PIP of each drug. DESIGN: Cost-utility analysis. We developed Markov models incorporating the AEs of each PIP, populated with published estimates of probabilities, health system costs (in 2014 euro) and utilities. PARTICIPANTS: A hypothetical cohort of 65 year olds analysed over 35 1-year cycles with discounting at 5% per year. OUTCOME MEASURES: Incremental cost, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios with 95% credible intervals (CIs, generated in probabilistic sensitivity analysis) between each PIP and an appropriate alternative strategy. Models were then used to evaluate the cost-effectiveness of potential interventions to reduce PIP for each of the three drug classes. RESULTS: All three PIP drugs and their AEs are associated with greater cost and fewer QALYs compared with alternatives. The largest reduction in QALYs and incremental cost was for benzodiazepines compared with no sedative medication (€3470, 95% CI €2434 to €5001; -0.07 QALYs, 95% CI -0.089 to -0.047), followed by NSAIDs relative to paracetamol (€806, 95% CI €415 and €1346; -0.07 QALYs, 95% CI -0.131 to -0.026), and maximal dose PPIs compared with maintenance dose PPIs (€989, 95% CI -€69 and €2127; -0.01 QALYs, 95% CI -0.029 to 0.003). For interventions to reduce PIP, at a willingness-to-pay of €45 000 per QALY, targeting NSAIDs would be cost-effective up to the highest intervention cost per person of €1971. For benzodiazepine and PPI interventions, the equivalent cost was €1480 and €831, respectively. CONCLUSIONS: Long-term benzodiazepine and NSAID prescribing are associated with significantly increased costs and reduced QALYs. Targeting inappropriate NSAID prescribing appears to be the most cost-effective PIP intervention.

Anti-inflammatory bowel effect of industrial orange by-products in DSS-treated mice.

This work addresses the role of different by-products derived from the industrial extraction of orange juice in a possible anti-inflammatory effect in mice with colitis induced by dextran sulfate sodium (DSS). Fresh orange residue (FOR), dry orange residue (DOR), orange liqueur (OL) and animal feed (AF), as well as commercial citrus pectin (CP), were administered to C57BL/6J mice for 15 days before starting the DSS treatment. Analysis of macroscopic parameters such as the Disease Activity Index (DAI) and the colonic weight/length ratio revealed an anti-inflammatory effect following intake of FOR, AF or CP. Moreover, q-PCR of RNA from colonic tissue indicated measurable changes in the expression of TNF-α, IL-1ß, iNOS, and intercellular adhesion molecules ICAM I, as well as in intestinal barrier proteins such as MUC-3, occludin, and ZO-1. Pectin, phenolic compounds and/or Maillard reaction products formed at initial steps were identified as relevant components exerting the ascribed beneficial effects. Our findings could open up the further application of a variety of orange by-products as food supplements in the potential amelioration of inflammatory bowel diseases.

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.

Cost-efficacy analysis of 3% diclofenac sodium, ingenol mebutate, and 3.75% imiquimod in the treatment of actinic keratosis.

Actinic keratosis (AK) is a clinical condition characterized by keratinocytic dysplastic lesions of the epidermis, affecting individuals chronically exposed to sunlight. Topical therapies allow the treatment of a whole area of affected skin and currently include diclofenac sodium gel, 5-fluorouracil cream, 5-fluorouracil and acetylsalicylic acid solution, imiquimod cream, and ingenol mebutate gel. Due to the comparable efficacy of 3% diclofenac, ingenol mebutate, and 3.75% imiquimod in treating AK multiple lesions, a pharmacoeconomic evaluation of cost-effectiveness of the three treatments was needed. A cost-efficacy analysis comparing 3% diclofenac sodium with ingenol mebutate and 3.75% imiquimod was performed. In this analysis, efficacy data were combined with quality-of-life measurement derived from previous studies as well as the costs associated with the management of these lesions in Italy. Patients' demographics and clinical characteristics were assumed to reflect those from the clinical studies considered.

Comparison of the Cost-utility Analysis of Electroacupuncture and Nonsteroidal Antiinflammatory Drugs in the Treatment of Chronic Low Back Pain.

INTRODUCTION AND OBJECTIVE: Chronic low back pain (CLBP) is among the most common and important reasons for visiting a spine surgeon by patients; it is the second cause of visiting a doctor. Low back pain can cause considerable suffering and is a major financial burden in the society. There are many different methods available for the treatment of CLBP. This study aimed to compare the cost-utility of electroacupuncture (EA) and nonsteroidal antiinflammatory drugs (NSAIDs), as two common treatment methods for patients with CLBP. METHODS: This study was conducted on 100 patients suffering from CLBP. Cases were randomly selected from patients referring to two hospitals and four acupuncture clinics in Tehran. Forty-one patients received EA, and 59 patients were prescribed NSAIDs. The EuroQol five dimensions questionnaire was used to calculate quality-adjusted life-year. For calculating the total cost of the two treatment methods, face to face interview with patients was conducted by the researchers (using specific basic literature questionnaire), neurologists, and spine surgeons. The study perspective was social (direct and indirect costs calculated). RESULTS: The mean age for EA group was 41 ± 2.3 years, and for NSAIDs group, it was 38.0 ± 4.4 years. The average of the utility of patients under treatment by EA and NSAIDs was estimated as 0.70 and 0.627, respectively. The difference in utility between the two groups was significant (p ≤ 0.05). The total cost of EA and NSAIDs was estimated as 461.48 ± 57.8$ and 497.77 ± 85.2$ for one year (2016), respectively, which was also significant (p ≤ 0.05). CONCLUSION: The results indicate a significant difference between EA and NSAIDs in cases of both utility and total cost. The findings demonstrate that EA is more cost-effective than NSAIDs, as therefore can be considered as an alternative treatment for CLBP, with reasonable cost-utility.

Current practice and usual care of major cervical disorders in Korea: A cross-sectional study of Korean health insurance review and assessment service national patient sample data.

Neck pain is a highly common condition and is the 4th major cause of years lived with disability. Previous literature has focused on the effect of specific treatments, and observations of actual practice are lacking to date. This study examined Korean health insurance review and assessment service (HIRA) claims data to the aim of assessing prevalence and comparing current medical practice and costs of cervical disorders in Korea.Current practice trends were determined through assessment of prevalence, total expenses, per-patient expense, average days in care, average days of visits, sociodemographic characteristics, distribution of medical costs, and frequency of treatment types of high frequency cervical disorders (cervical sprain/strain, cervical intervertebral disc displacement [IDD], and cervicalgia).Although the number of cervical IDD patients was few, total expenses, per-patient expense, average days in care, and average days of visits were highest. The proportion of women was higher than men in all 3 groups with highest prevalence in the ≥50s middle-aged population for IDD compared to sprain/strain. Primary care settings were commonly used for ambulatory care, of which approximately 70% chose orthopedic specialist treatment. In analysis of medical expenditure distribution, costs of visit (consultation) (22%-34%) and physical therapy (14%-16%) were in the top 3 for all 3 disorders. Although heat and electrical therapies were the most frequently used physical therapies, traction use was high in the cervical IDD group. In nonnarcotics, aceclofenac and diclofenac were the most commonly used NSAIDs, and pethidine was their counterpart in narcotics.This study investigated practice trends and cost distribution of treatment regimens for major cervical disorders, providing current usage patterns to healthcare policy decision makers, and the detailed treatment reports are expected to be of use to clinicians and researchers in understanding current usual care.

Intra articular hyaluronic acid in the management of knee osteoarthritis: Pharmaco-economic study from the perspective of the national health insurance system.

INTRODUCTION: Pharmaco-economic data on the management of knee osteoarthritis (OA) with intra articular hyaluronic acid (IA HA) viscosupplementation is limited. We contrasted IA HA with non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Observational, prospective and multicenter study comparing treatments of knee OA costs and efficacy with either NSAIDs alone, or hyaluronic acid (Arthrum H 2%®), during a 6-month follow-up period. The investigators were pharmacists who recorded data on disease, drug consumption and healthcare circuit. Retrospectively, the 6-month period preceding inclusion was also studied, to ensure the comparability of groups. RESULTS: 199 patients were analyzed in a NSAIDs group and 202 in an IA HA group. Any of the WOMAC sub-scores and the EQ-5D Quality of Life index were significantly improved in the IA HA group (p<0.0001) at 3 and 6 months. Clinical results were therefore in favor of the IA HA group. The total drug expenses per 6-month period were comparable before and after inclusion, €96 and €98 for NSAIDs group vs €94 and €101 for IA HA group, which indicates no evidence of additional cost from IA HA. For the active part of the population, the incidence of sick leave was lower in the IA HA group, indicating a better maintenance of patient activity. The overall expense on 12 months (6 months before and 6 months after inclusion) for the national health insurance system was comparable for NSAIDs and IA HA groups: €528 and €526, respectively. The number of patients taking NSAIDs significantly decreased in IA HA group (from 100% at inclusion to 66% at 1-3 months and 44% at 4-6 months), but remained unchanged (100%) during the follow-up period, in NSAIDs group. CONCLUSION: Treatment with IA HA did not generate additional cost for the national health insurance and was associated with a functional improvement of knee osteoarthritis and Quality of Life. The cost-utility analysis was in favor of IA HA, with a gain of QALY equivalent to half a month, after the 6-month follow-up period comparing both treatments. The NSAIDs consumption was decreased in the IA HA group, resulting in an improved estimated benefit/risk ratio.

Health economic analyses of psoriasis management: a systematic literature search.

In the course of the chronic skin disease psoriasis, where a variety of treatment interventions is available, a strong growth of health economic studies comparing treatment costs and benefits can be noticed. The objective was to identify health economic evaluations of psoriasis treatments that have been published to date. Of particular interest were the mostly used analysis and outcome parameters, the compared treatments, and the question, if available health economic studies may be used to perform a meta-analysis of qualitative findings. A systematic literature search using PubMed Medline, Ovid Medline, and Cochrane Library was performed for articles, published and available until mid of January 2016. Among the key words were the terms "psoriasis" and "cost-effectiveness". The search resulted in 318 articles without duplicates. Thereof 60 health economic analyses in psoriasis management were identified. Most of these are cost-effectiveness evaluations (45). The clinical parameter PASI (Psoriasis Area Severity Index) is the most often used cost-effectiveness outcome (33) followed by the Dermatology Life Quality Index (DLQI) (6). In case of cost-utility analyses, QALYs (quality-adjusted life-years) were mostly generated with the help of EuroQol five dimensions questionnaire (EQ-5D) (12), which was partly based on PASI and DLQI values. The majority of health economic studies is focusing on the direct medical and non-medical costs without consideration of productivity losses. Almost 70 % of 60 publications were conducted in Europe. Overall, most considered systemic treatments were the biological agents etanercept (36), adalimumab (27), and infliximab (26) followed by ustekinumab (17) and phototherapy (incl. UV-B, PUVA/psoralen combined with UV-A) (14). Comparisons including only topical treatments mostly focused on vitamin D treatment (14), corticosteroids (13), and coal tar products (6) followed by dithranol (5) and tazarotene (4). Given the setting, compared treatments, and study conditions, different results can be found for medical decision-making. Thereby, it can be noted that there are no standards on methods and outcomes measures available. This leads to a very limited comparability of health economic studies and presents no comfortable basis to examine a meta-analysis of health economic results. The presented systematic review shows the need for nationwide data and interpretation.

Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications.

Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate ("5-ASA"), mesalamine suppository, or mesalamine enema ("UP Rx"). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations.

[Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective]. / Análisis coste-efectividad de celecoxib frente a antiinflamatorios no esteroideos no selectivos en el tratamiento de la artrosis en España: una perspectiva actual.

OBJECTIVE: To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. METHODS: A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons¼ trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. RESULTS: Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (p<.001), with mean incremental cost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. CONCLUSION: Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS.

Cost-effectiveness of aspirin adjuvant therapy in early stage colorectal cancer in older patients.

BACKGROUND & AIMS: Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older. METHODS: Two five-state Markov models were constructed separately for Stage I and II colorectal cancer using TreeAge Pro 2014. Two hypothetical cohorts of 10,000 individuals at a starting age of 65 years and with colorectal cancer in remission were put through the models separately. Cost-effectiveness of aspirin was evaluated against no treatment (Stage I and II) and capecitabine (Stage II) over a 20-year period from the United States societal perspective. Extensive one-way sensitivity analyses and multivariable Probabilistic Sensitivity Analyses (PSA) were performed. RESULTS: In the base case analyses, aspirin was cheaper and more effective compared to other comparators in both stages. Sensitivity analyses showed that no treatment and capecitabine (Stage II only) can be cost-effective alternatives if the utility of taking aspirin is below 0.909, aspirin's annual fatal adverse event probability exceeds 0.57%, aspirin's relative risk of disease progression is 0.997 or more, or when capecitabine's relative risk of disease progression is less than 0.228. Probabilistic Sensitivity Analyses (PSA) further showed that aspirin could be cost-effective 50% to 80% of the time when the willingness-to-pay threshold was varied from USD 20,000 to USD 100,000. CONCLUSION: Even with a modest treatment benefit, aspirin is likely to be cost-effective in Stage I and II colorectal cancer, thus suggesting a potential unique role in secondary prevention in this group of patients.

Phenolic-enriched fractions from brewers' spent grain possess cellular antioxidant and immunomodulatory effects in cell culture model systems.

BACKGROUND: Large quantities of brewers' spent grain (BSG), a co-product of the brewing industry, are produced annually. BSG contains hydroxycinnamic acids, and phenolic-rich extracts from BSG have previously demonstrated the ability to protect against oxidant-induced DNA damage. The present study investigated the anti-inflammatory potential of eight phenolic extracts from BSG: four pale (P1-P4) and four black (B1-B4) extracts. RESULTS: BSG extracts were more cytotoxic in Jurkat T than U937 cells, with lower IC50 values in Jurkat T cells, measured using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Pale BSG extracts P2 and P3 showed the greatest anti-inflammatory potential, significantly (P < 0.05) reducing interleukin-2 (IL-2), interleukin-4 (IL-4, P2 only), interleukin-10 (IL-10) and interferon-γ (IFN-γ) production. In addition, extracts P1-P3 and B2-B4 showed significant (P < 0.05) antioxidant effects, determined by the cellular antioxidant activity assays superoxide dismutase, catalase and glutathione content (GSH). CONCLUSION: Phenolic extracts from BSG, particularly the pale BSG extracts, have the ability to reduce a stimulated cytokine production and may also protect against cellular oxidative stress. Results of the present study highlight the potential of BSG phenolic extracts to act as functional food ingredients, providing an alternative use and improving the value of this brewing industry co-product.

Can mucosal healing be a cost-effective endpoint for biologic therapy in Crohn's disease? A decision analysis.

BACKGROUND: Observational studies have demonstrated that mucosal healing (MH) may be associated with reductions in hospitalizations and surgeries for moderate to severe Crohn's disease (CD). Whether treatment to achieve MH is a cost-effective endpoint has not been established previously. METHODS: We constructed a decision analytic model comparing two treatment strategies. In the clinical response (CR) arm, patients not in clinical remission at year 1 are dose-escalated. In the MH arm, patients with persistence of mucosal ulcerations at year 1 are escalated irrespective of clinical symptoms. Patients remain at risk for hospitalization and surgeries while they have active disease. We examined a 2-year time horizon. RESULTS: In the base case the MH strategy was more effective at 2 years (quality-adjusted life year [QALY] 0.71) compared to the CR strategy (QALY 0.69) but was also more expensive with an incremental cost-effectiveness ratio (ICER) of $49,278/QALY gained. In a hypothetical cohort of 100,000 patients assigned to each treatment arm, the MH strategy resulted in lower rates of hospitalization and surgery with a number needed to treat of 27 and 106, respectively. The results were sensitive to the ability of infliximab to achieve MH and the incremental benefit of MH over clinical remission. CONCLUSIONS: We demonstrate that MH as an endpoint is a cost-effective strategy in CD patients initiating IFX therapy. Further prospective studies on durability of MH and its incremental benefit as well as the ability of other available biologic agents to achieve MH are necessary to validate our findings.

NMR spectrometry isotopic fingerprinting: a tool for the manufacturer for tracking active pharmaceutical ingredients from starting materials to final medicines.

In the frame of increasingly stringent quality assessment required by the regulators, the pharmaceutical industry has to face increasingly sophisticated counterfeiting practices. Counterfeits based on deliberate copying of processes or on the infringement of current patents for generic medicines are not straightforward to detect, unless the molecular probe is the active molecule itself. In this context, impurity profiling is limited. A tool based on the determination of intramolecular isotopic profiles has been developed to provide manufacturers of APIs (Active Pharmaceutical Ingredients) with a new solution to meet this double requirement. Stable isotope analyses by NMR gives direct access to site-specific isotope content at natural abundance. In this report, it is shown how both ²H and ¹³C NMR spectrometry can provide complementary and valuable information that could be applied to link APIs to their manufacturing source. Isotopic ¹³C NMR offers additional benefits over ²H NMR in using robust adiabatic polarization transfer methods, leading to a tremendous reduction in experimental time. Two approaches are illustrated. Firstly, the use of ²H and single pulse ¹³C NMR spectra obtained on 20 commercial ibuprofen samples from different origins show that this combined strategy leads to (i) a unique intramolecular isotope identification and (ii) a preliminary classification of the samples according to the synthetic pathways of the main industrial processes. An approach employing polarization transfer methods applied to 11 commercial naproxen samples, for which ²H and single pulse ¹³C NMR spectra are not exploitable and/or are not accessible in reasonable time. The relative and partial intramolecular ¹³C distribution obtained on naproxen by applying this methodology is sufficiently informative to allow the same conclusions as for ibuprofen. The additional benefits that these approaches should bring to API manufacturers are discussed.

Combination aspirin and/or calcium chemoprevention with colonoscopy in colorectal cancer prevention: cost-effectiveness analyses.

BACKGROUND: Clinical and cohort studies have shown that low-dose aspirin and calcium are effective low-risk strategies for primary prevention of colorectal cancer (CRC). We compared the cost-effectiveness of aspirin and calcium chemoprevention used with colonoscopy for primary prevention of CRCs. METHODS: Markov chain Monte Carlo simulations for a population of 100,000 persons, with a colonoscopy compliance rate of 50%, were used for the analysis. If adenomas were detected, colonoscopy was repeated every 4 years until no adenomas were evident. Data sources included adenoma transition rates, initial adenoma and CRC incidences, and treatment complication rates from existing literature. Age-adjusted U.S. standard population mortality rates were used and costs were from Medicare reimbursement data. The target population was U.S. adults, undergoing CRC screening from ages 50 to 75 years. RESULTS: Outcomes included incremental cost-effectiveness ratios (ICER), life-years saved (LYS), and cancer-free years saved (CFYS). The ICER per LYS for colonoscopy alone dominated compared with no screening. Compared with colonoscopy alone, colonoscopies with aspirin (ICER = $12,950/LYS) or calcium (ICER = $13,041/LYS) were the next most cost-effective strategies. ICERs per CFYS were $3,061 and $2,317 for aspirin and calcium, respectively, when added to colonoscopy. Sensitivity analyses indicated that initial prevalence of adenomas was a main determinant of prevention cost-effectiveness. CONCLUSION: Low-dose aspirin or calcium supplementation may be beneficial when added to colonoscopy, for optimum CRC prevention, at small incremental costs. IMPACT: Cost-effectiveness analyses suggest that aspirin and calcium in combination with colonoscopies are cost-effective for CRC prevention in average-risk populations.

Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings.

OBJECTIVE: To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). METHODS: The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. RESULTS: Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, <3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs. CONCLUSIONS: Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management.

A new perspective on the pharmacoeconomics of colchicine.

BACKGROUND: Gout is a common inflammatory arthritis that affects ∼4% of the US population. Most patients with gout are >50 years of age and have multiple comorbidities. Gout is caused by the deposition of monosodium urate crystals in joints secondary to hyperuricemia. Gout typically presents as an acute painful inflammation (flare) involving one or more joint. Left untreated it can progress into a more chronic polyarthritis. Acute gout flare treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. The safety and efficacy of colchicine, especially in the presence of comorbidity and potential contraindications, has only recently been systematically investigated. METHODS: Through the use of a systematic computer-based literature analysis, this pharmacoeconomic review evaluated costs, risks, and benefits of Colcrys (colchicine) compared with other treatments for gout in the US. RESULTS: Both colchicine and NSAIDs are historically associated with gastrointestinal (GI) adverse events (AEs). Colchicine has very low risk for AEs, even in patients with GI disorders; whereas, NSAIDS are contraindicated in patients with GI disorders, renal insufficiency, and heart failure. The monthly cost of treating 100 patients with Colcrys was $33,100 compared with $3000 for NSAIDs. However, hospitalization for GI complications (1.8%) and heart failure (1.9%) is common with NSAIDs and can increase the monthly cost of treating 100 patients with NSAIDs to $161,000, considering $15,000-20,000 per day of hospitalization. CONCLUSIONS: Considering high costs associated with treating patients with gout, it seems prudent to choose the treatment with greatest benefit, lowest cost, and least risk. Despite higher cost per dose, colchicine appears to be more cost effective for management of gout flares than NSAIDs.

A rapid LC/MS/MS method for the analysis of nonvolatile antiinflammatory agents from Mentha spp.

UNLABELLED: Mints (Mentha spp.), aromatic crops grown largely for their essential oils, also are rich sources of nonvolatile antiinflammatory agents. Identification and quantitation of the constituents responsible for their antiinflammatory activity is challenging owing to the lack of suitable chromatographic methodology. In the present research, the simultaneous quantitation of antiinflammatory constituents rosmarinic acid, oleanolic acid, and ursolic acid in mints was attained by using a unique tandem HPLC column system coupled with an electrospray ionization mass detection (MRM mode). The ion mode optimization for rosmarinic acid under negative and triterpenoid acids under positive was achieved by setting 2 time segments in a single run where the polarity mode was switched from negative (0 to 10 min) to positive (10 to 40 min). For the investigated concentration ranges of antiinflammatory agents in mints, good linearities (r² ≥ 0.998) were obtained for each calibration curve. Validation of precision and accuracy for this method showed that intra- and inter-day repeatabilities for all analytes were less than 5.51%, and the recoveries varied from 97.8% to 99.3%. The developed LC/MS/MS assay provides a suitable quality control method for the determination of antiinflammatory constituents in Mentha spp. There is a wide range of diversity in the natural product composition for these acids across the Mentha germplasm collection evaluated. The presence of these antiinflammatory acids in post-distilled mints shows that value-added nutraceutical enriched products can be developed with proper processing and recovery systems in addition to the distillation and capture of the valuable volatile essential oils. PRACTICAL APPLICATION: Results from this research would benefit both commercial farmers growing mint for essential oil and those in the food industry where value-added phytopharmaceutical enriched products can be developed with proper processing, quality control, and recovery systems during mint essential oil distillation.

Nonsteroidal anti-inflammatory drugs and colchicine to prevent gout flare during early urate-lowering therapy: perspectives on alternative therapies and costs.

Published evidence in the literature, regulatory status, and relative costs of colchicine and nonsteroidal anti-inflammatory drugs (NSAIDs) for prophylaxis of gouty flares during early urate-lowering therapy are reviewed.