A Double-Blind, Randomized Controlled Trial of Pre-incision Wound Infiltration Using Diclofenac Versus Bupivacaine for Post-operative Pain Relief in Open Thyroid and Parathyroid Surgery.

BACKGROUND: Pre-incision wound infiltration using NSAID is an alternative method to manage post-operative pain in surgery. It is postulated that NSAID delivered peripherally exerts efficient analgesic and anti-inflammatory effect with minimal systemic complication. This study explored the efficacy of using diclofenac for wound infiltration in open thyroidectomy and parathyroidectomy as compared to conventional agent, bupivacaine. METHODOLOGY: The study was designed as a double-blind, randomized controlled trial involving 94 patients who underwent open thyroidectomy or parathyroidectomy in Hospital Pulau Pinang, Malaysia, from November 2015 to November 2016. The study compared the efficacy of pre-incision wound infiltration of diclofenac (n = 47) versus bupivacaine (n = 47) in post-operative pain relief. Wound infiltration is given prior to skin incision. Mean pain score at designated time interval within the 24-h post-operative period, time to first analgesia, total analgesic usage and total analgesic cost were assessed. RESULTS: Ninety-four patients were recruited with no dropouts. Mean age was 49.3 (SD = 14.2) with majority being female (74.5%). Ethnic distribution recorded 42.6% Chinese, 38.3% Malay, followed by 19.1% Indian. Mean duration of surgery was 123.8 min (SD = 56.5), and mean length of hospital stay was 4.7 days (SD = 1.8). The characteristics of patient in both groups were generally comparable except that there were more cases of total thyroidectomy in the diclofenac group (n = 31) as compared to the bupivacaine group (n = 16). Mean pain score peaked at immediate post-operative period (post-operative 0.5 h) with a score of 3.5 out of 10 and the level decreased steadily over the next 20 h starting from 4 h post-operatively. Pre-incision wound infiltration using diclofenac had better pain control as compared to bupivacaine at all time interval assessed. In the resting state, the mean post-operative pain score difference was statistically significant at 2 h [2.1 (SD = 1.5) vs. 2.8 (SD = 1.8), p = 0.04]. During neck movement, the dynamic pain score difference was statistically significant at post-operative 1 h [2.7 (SD = 1.9) vs. 3.7 (SD = 2.1), p = 0.02]; 2 h [2.7 (SD = 1.6) vs. 3.7 (SD = 2.0), p = 0.01]; 4 h [2.2 (SD = 1.5) vs. 2.9 (SD = 1.7), p = 0.04], 6 h [1.9 (SD = 1.4) vs. 2.5 (SD = 1.6), p = 0.04] and 12 h [1.5 (SD = 1.5) vs. 2.2 (SD = 1.4), p = 0.03]. Mean dose of tramadol used as rescue analgesia in 24 h duration was lower in the diclofenac group as compared to bupivacaine group [13.8 mg (SD = 24.9) vs. 36.2 mg (SD = 45.1), p = 0.01]. The total cost of analgesia used was significantly cheaper in diclofenac group as compared to bupivacaine group [RM 3.47 (SD = 1.51) vs. RM 13.43 (SD = 1.68), p < 0.01] or [USD 0.83 (SD = 0.36) vs. USD 3.21 (SD = 0.40), p < 0.01]. CONCLUSION: Pre-incision wound infiltration using diclofenac provides better post-operative pain relief compared to bupivacaine for patient who had underwent open thyroidectomy or parathyroidectomy. Diclofenac is cheap and easily available in the limited resource setting. This approach offers a superior alternative for post-operative pain relief as compared to bupivacaine.

Evaluation of the treatment costs and duration of topical treatments for multiple actinic keratosis based on the area of the cancerization field and not on the number of lesions.

BACKGROUND: The cost of topical treatments for actinic keratosis (AK) has historically been evaluated in relation to the number of lesions requiring treatment or simply by the price of a single tube/sachet of the drug used. OBJECTIVE: To demonstrate a new method of costing topical treatments in AK, which takes into account the actual cancerization area treated. METHODS: In order to evaluate the actual cost of each treatment, the official approval status of the drug was used to estimate the amount of cream needed per one cm2 . This value was then applied to the hypothetical cancerization area sizes to demonstrate the impact of the size treated on the actual cost of treatment. The price considered was the ex-factory price in Italy. RESULTS: Areas which could be treated with a single tube/sachet of Metvix® , Picato® , Aldara® , Solaraze® and Zyclara® were 200, 25, 25, 33.3 and 200 cm2 , respectively. For the treatment of smaller areas (<100 cm2 ), treatment with Metvix® was the most costly topical option in Italy. However, for the treatment of cancerization areas larger than 100 cm2 , Metvix® was the least expensive treatment option. Treatment with Metvix® was least long, requiring a single day of treatment for an area of up to 200 cm2 , compared with up to 224 days of treatment with Aldara® for the treatment of a similar size. CONCLUSION: Changing treatment costing strategy in the management of multiple AKs towards costing per cancerization area instead of costing per lesion is a much more accurate representation of the 'real world cost' for AK.

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.

Cost-effectiveness of Ingenol Mebutate Gel for the Treatment of Actinic Keratosis in Greece.

PURPOSE: The present study aimed to perform a cost-effectiveness analysis of ingenol mebutate (IM) versus other topical alternatives for the treatment of actinic keratosis (AK). METHODS: The analysis used a decision tree to calculate the clinical effects and costs of AK first-line treatments, IM (2-3 days), diclofenac 3% (for 8 or 12 weeks), imiquimod 5% (for 4 or 8 weeks), during a 24-month horizon, using discrete intervals of 6 months. A hypothetical cohort of immunocompetent adult patients with clinically confirmed AK on the face and scalp or trunk and extremities was considered. Clinical data on the relative efficacy were obtained from a network meta-analysis. Inputs concerning resource use derived from an expert panel. All costs were calculated from a Greek third-party payer perspective. FINDINGS: IM 0.015% and 0.05% were both cost-effective compared with diclofenac and below a willingness-to-pay threshold of €30,000 per quality-adjusted life-year (QALY) (€199 and €167 per QALY, respectively). Comparing IM on the face and scalp AK lesions for 3 days versus imiquimod for 4 weeks resulted in an incremental cost-effectiveness ratio of €10,868 per QALY. IM was dominant during the 8-week imiquimod period. IM use on the trunk and extremities compared with diclofenac (8 or 12 weeks) led to incremental cost-effectiveness ratios estimated at €1584 and €1316 per QALY accordingly. Results remained robust to deterministic and probabilistic sensitivity analyses. IMPLICATIONS: From a social insurance perspective in Greece, IM 0.015% and IM 0.05% could be the most cost-effective first-line topical field treatment options in all cases for AK treatment.

Cost-effectiveness of Low-dose Submicron Diclofenac Compared With Generic Diclofenac.

PURPOSE: NSAIDs are commonly prescribed for the treatment of pain and inflammation. Despite the effectiveness of NSAIDs, concerns exist regarding their tolerability. Worldwide health authorities, including the European Medicines Agency, Health Canada, and the US Food and Drug Administration, have advised that NSAIDs be prescribed at the lowest effective dosage and for the shortest duration. Effective lowering of NSAID dosage without compromising pain relief has been demonstrated in randomized, controlled trials of the recently approved NSAID lower-dose submicron diclofenac. Building on previously published work from an independently published systematic review and meta-analysis, a linear dose-toxicity relationship between diclofenac dose and serious gastrointestinal (GI) events was recently demonstrated, indicating that reductions in adverse events (AEs) may be seen even with modest dose reductions in many patients. The objective of the present study was to estimate the potential reduction in risk for NSAID dose-related AEs, corresponding savings in health care costs, and the incremental cost-effectiveness of submicron diclofenac compared with generic diclofenac in the United States. METHODS: Our decision-analytic cost-effectiveness model considered a subset of potential AEs that may be avoided by lowering NSAID dosage. To estimate the expected reductions in upper GI bleeding/perforation and major cardiovascular events with submicron diclofenac, our model used prediction equations estimated by meta-regressions using data from systematic literature reviews. Utilities, lifetime costs, and health outcomes associated with AEs were estimated using data from the literature. The face validity of the model structure and inputs was confirmed by clinical experts in the United States. Results were evaluated in 1-way and probabilistic sensitivity analyses. FINDINGS: The model predicted that submicron diclofenac versus generic diclofenac could reduce the occurrence of modeled GI events (by 18.0%), cardiovascular events (by 6.9%), and acute renal failure (by 18.8%), leading to a 9.8% reduction in costs of treating AEs. Submicron diclofenac was predicted to be cost-saving, with results relatively insensitive to parameter uncertainty. IMPLICATIONS: Submicron diclofenac has the potential to provide clinical and economic value to patients using NSAIDs in the United States. Further investigation regarding the potential effects of submicron diclofenac on the risks for additional NSAID dose-related toxicities should be explored.

Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain. / Análisis de coste-efectividad y coste-utilidad de ingenol mebutato versus diclofenaco 3% e imiquimod 5% en el tratamiento de la queratosis actínica en España.

OBJECTIVE: To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain. METHODS: We used an adapted Markov model to simulate outcomes in a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The effectiveness of ingenol mebutate-with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively-was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 additional clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod. CONCLUSIONS: Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<€30000/quality-adjusted life-years).

A cost-utility analysis of ingenol mebutate gel for the treatment of actinic keratosis: a Scottish perspective.

BACKGROUND: Actinic keratosis (AK) is a UV-induced, pre-malignant skin condition that is common in adults over 60 years of age with fair skin in Scotland. The most commonly prescribed first-line treatment for AK in Scotland is currently diclofenac gel (3 %). Ingenol mebutate gel is a recently developed topical therapy available in two strengths for the treatment of AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days). OBJECTIVE: To compare the cost-effectiveness of two strengths of ingenol mebutate gel developed to treat AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days) with other first-line AK therapies including diclofenac gel, 5-FU, 5-FU/salicylic acid, and cryotherapy for the first-line treatment of AK in adult patients, from the perspective of the National Health Service (NHS) in Scotland. METHODS: A cost-utility analysis was conducted using a decision-tree approach to calculate the costs and benefits of different treatment strategies for AK on the face and scalp or trunk and limbs over a 12-month time horizon. Data on the relative efficacy of treatments were obtained from a systematic literature review and meta-analysis. Utility scores and resource-use data were obtained from published sources. RESULTS: Over 12 months, ingenol mebutate 150 mcg/g gel and 500 mcg/g gel were cost-effective compared with the most commonly used topical therapy in Scotland, diclofenac (3 %) gel, at a willingness-to-pay threshold of £20,000 per QALY, with a minimal additional cost of £43 and £105, respectively per QALY gained. CONCLUSIONS: Ingenol mebutate gel is a cost-effective therapy for the first-line treatment of AK from a Scottish NHS perspective.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a cost-effectiveness analysis.

OBJECTIVES: The aim of the present study was to perform a comparative cost-effectiveness analysis of the different strategies used to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis. METHODS: We performed a cost-effectiveness decision analysis of 4 prophylactic strategies (nonsteroidal anti-inflammatory drugs or NSAIDs, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis) in a simulated cohort of 300 patients during 1 year. Treatment effectiveness was defined as the number of patients who did not develop post-ERCP pancreatitis. RESULTS: The baseline costs of each strategy were as follows: rectal NSAID $359,098, pancreatic stent $426,504, stent plus rectal indomethacin $479,153, and no prophylaxis $491,275. The mean number of cases developing post-ERCP pancreatitis was 16, 21, 23, and 37 for the strategies rectal NSAID, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis, respectively. Taking rectal NSAID prophylaxis as the reference strategy, the odds ratio of an episode of post-ERCP acute pancreatitis after pancreatic stent placement was 1.33 (95% confidence interval [CI], 0.68-2.61); after stent plus indomethacin, it was 1.40 (95% CI, 0.72-2.73), and after no prophylaxis, it was 2.49 (95% CI, 1.35-4.59). CONCLUSIONS: Rectal NSAID administration proved to be the most cost-effective prophylactic strategy used to prevent post-ERCP pancreatitis. The strategy of no prophylaxis for this complication should be avoided.

A cost-effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model.

OBJECTIVES: Celecoxib for the treatment of pain resulting from osteoarthritis (OA) was reviewed by the Tandvårds- och läkemedelsförmånsverket-Dental and Pharmaceutical Benefits Board (TLV) in Sweden in late 2010. This study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus a PPI in a Swedish setting. METHODS: The National Institute for Health and Care Excellence (NICE) in the UK developed a health economic model as part of their 2008 assessment of treatments for OA. In this analysis, the model was reconstructed and adapted to a Swedish perspective. Drug costs were updated using the TLV database. Adverse event costs were calculated using the regional price list of Southern Sweden and the standard treatment guidelines from the county council of Stockholm. Costs for treating cardiovascular (CV) events were taken from the Swedish DRG codes and the literature. RESULTS: Over a patient's lifetime treatment with celecoxib plus a PPI was associated with a quality-adjusted life year (QALY) gain of 0.006 per patient when compared to diclofenac plus a PPI. There was an increase in discounted costs of 529 kr per patient, which resulted in an incremental cost-effectiveness ratio (ICER) of 82,313 kr ($12,141). Sensitivity analysis showed that treatment was more cost effective in patients with an increased risk of bleeding or gastrointestinal (GI) complications. CONCLUSIONS: The results suggest that celecoxib plus a PPI is a cost effective treatment for OA when compared to diclofenac plus a PPI. Treatment is shown to be more cost effective in Sweden for patients with a high risk of bleeding or GI complications. It was in this population that the TLV gave a positive recommendation. There are known limitations on efficacy in the original NICE model.

A randomized clinical trial of photodynamic therapy with methyl aminolaevulinate vs. diclofenac 3% plus hyaluronic acid gel for the treatment of multiple actinic keratoses of the face and scalp.

BACKGROUND: A gel containing diclofenac and hyaluronic acid (DHA) and photodynamic therapy with methyl aminolaevulinate (MAL-PDT) are widely used treatments for actinic keratoses (AKs). OBJECTIVES: The aim of this single-centre, open-label, prospective, nonsponsored, randomized controlled clinical trial was to compare the treatment results and cost-effectiveness of MAL-PDT and DHA. METHODS: Patients with multiple AKs of the face and scalp were randomized to receive MAL-PDT or DHA. After 90 days, the overall complete remission (CR) rate of patients and the CR rate of lesions according to thickness score were assessed, and patients and an investigator scored the cosmetic outcome. In addition, patients scored their overall satisfaction with the treatment. Patients with CR of all lesions were followed up for 12 months. RESULTS: Two hundred patients with a total of 1674 AKs were enrolled. The lesion CR rates at 3 months were 85·9% with MAL-PDT and 51·8% with DHA (P < 0·0001). AKs of all thicknesses were significantly more responsive to MAL-PDT. The patient CR rates at 3 months were 68% with MAL-PDT and 27% with DHA. At the 12-month examination, the number of patients with CR reduced to 37 with MAL-PDT and seven with DHA. Rating of cosmetic outcome was very good or excellent in the vast majority of patients with both treatments. The analysis of cost-effectiveness showed that the costs per patient with CR at 3 months and at 12 months are €566·7 and €1026·2, respectively, with MAL-PDT and €595·2 and €2295·6, respectively, with DHA. CONCLUSIONS: Efficacy, cosmetic outcome and patients' overall satisfaction with MAL-PDT are superior in comparison with DHA. MAL-PDT is more expensive but it is more cost-effective.

The cost-effectiveness of celecoxib vs diclofenac in the treatment of osteoarthritis in the UK; an update to the NICE model using data from the CONDOR trial.

OBJECTIVES: The National Institute for Health and Clinical Excellence (NICE) health economic model for assessing the cost-effectiveness of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus PPI in the treatment of osteoarthritis has been updated using new adverse event (AE) risks from the CONDOR trial. In light of this new information, this study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus PPI compared to diclofenac plus PPI. METHODS: NICE developed a health economic model as part of their 2008 multiple technology assessment of treatments for osteoarthritis. The model was adapted for this study to update the relative risks of adverse events, using data from the CONDOR trial. RESULTS: Using the AE data from the CLASS trial alone, celecoxib plus PPI has an ICER of £9538 per QALY when compared to diclofenac plus PPI. When the AE data from CONDOR alone is used, this ICER decreases to £4773 per QALY. Using the pooled data from both trials, celecoxib plus PPI has an ICER of £9377 per QALY compared to diclofenac plus PPI. DISCUSSION: The results suggest that when new AE risks are used, celecoxib plus PPI remains a cost-effective treatment for OA when compared to diclofenac plus PPI. However, this analysis is limited by the short time horizon, and additional AEs that have not been considered.

Cost-effectiveness analysis of topical treatments for actinic keratosis in the perspective of the Italian health care system.

Actinic keratosis (AK) is the most common cutaneous malignant neoplasm and its prevalence continues to increase. According to the most recent findings, AK is currently considered the initial stage, in situ, of squamous cell carcinoma. Field-directed therapies for AKs are the preferred treatment since they have the advantage to clear the clinically visible lesions and also subclinical lesions within the cancerous field. We assessed the cost-effectiveness of topical treatments for AKs including 3% diclofenac in 2.5% hyaluronic acid (HA) gel, imiquimod 5% cream and photodynamic therapy with methyl aminolevulinate (MAL-PDT) in the perspective of the Italian Health Care System (SSN). We used a decision tree analytical approach and efficacy data were drawn from published clinical trials. Cost was evaluated from the SSN perspective during a time horizon of 3 months. A responder was defined as a patient with all lesions clinically cleared and showing an excellent cosmetic result. Based on the applied model, the cost per complete responder was calculated. Diclofenac 3% in HA was less expensive (Euro 256) than MAL-PDT (Euro 320) and imiquimod (Euro 342). Effectiveness was similar and better for diclofenac 3% in HA and MAL-PDT (0.813%) in comparison to 0.734% of imiquimod, respectively. The one-way and probabilistic sensitivity analyses confirmed the results of base case scenario. Based on this cost-effectiveness model, diclofenac 3% in HA can be considered the treatment of choice for AK lesions and surrounding field under a pharmacoeconomic point of view.

[Postoperative multimodal pain management : Cost-minimisation analysis from a hospital's point of view]. / Multimodale postoperative Schmerztherapie : Kostenminimierungsanalyse aus Krankenhausperspektive.

BACKGROUND: Adequate pain management after major surgery is important to improve patients' quality of life and to support the healing process. Since the cost for pain management is included in the DRG system for hospital reimbursement, hospitals should aim to provide adequate postoperative pain management at the lowest possible cost. In this study we compare two multimodal pain management schemes for postoperative pain management in a cost-minimisation analysis. METHODS: In a decision analytic model two treatment regimes for postoperative pain management are compared in a cost-minimisation analysis: diclofenac + morphine vs paracetamol vs morphine. The study is performed from the perspective of a public hospital. Due to the short time horizon costs are not discounted. RESULTS: Assuming comparable effectiveness for adequate postoperative pain management, the expected value in the decision tree model for the combination diclofenac + morphine is 13.37 EUR and for the combination paracetamol + morphine 32.23 EUR, respectively. The results are robust under various one- and two-way sensitivity analyses. CONCLUSION: With no contraindications given the combination diclofenac + morphine is more cost-effective for postoperative pain management after major surgery compared to paracetamol + morphine.

Cost effectiveness of etoricoxib versus celecoxib and non-selective NSAIDS in the treatment of ankylosing spondylitis.

To evaluate the cost effectiveness of etoricoxib (90 mg/day) relative to celecoxib (200 or 400 mg/day), and the non-selective NSAIDs naproxen (1000 mg/day) and diclofenac (150 mg/day) in the initial treatment of ankylosing spondylitis (AS) from the UK NHS perspective. A Bayesian cost-effectiveness model was developed to estimate the costs and benefits associated with initiating AS treatment with etoricoxib, celecoxib, diclofenac or naproxen. Efficacy, safety and medical resource and cost data were obtained from the literature. The obtained efficacy estimates were synthesized with a mixed treatment comparison meta-analysis. Treatment benefit and degree of disease activity, as reflected with Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, were related to QALYs and AS-specific costs (related to BASDAI). Other cost outcomes related to drug acquisition, and gastrointestinal and cardiovascular safety. Uncertainty in the source data was translated into uncertainty in cost-effectiveness estimates and therefore decision uncertainty. Costs and outcomes were discounted at 3.5% per annum. There was a >98% probability that treatment with etoricoxib results in greater QALYs than the other interventions. Over a 30-year time horizon, starting AS treatment with etoricoxib was associated with about 0.4 more QALYs than the other interventions. At 2 years there was a 77% probability that etoricoxib had the lowest cost. This increased to >99% at 30 years. Etoricoxib is expected to save 13 620 UK pounds (year 2007 values) relative to celecoxib (200/400 mg), 9957 UK pounds relative to diclofenac and 9863 UK pounds relative to naproxen. For a willingness-to-pay ceiling ratio of 20 000 UK pounds per QALY, there was a >97% probability that etoricoxib was the most cost-effective treatment. Additional analysis with different assumptions, including celecoxib 200 mg, and ignoring cost-offsets associated with improvements in disease activity, supported these findings. This economic evaluation suggests that, from the UK NHS perspective, etoricoxib is the most cost-effective initial NSAID treatment for AS patients.

A randomized, multicentre, double-blind, parallel-group study to assess the adverse event-related discontinuation rate with celecoxib and diclofenac in elderly patients with osteoarthritis.

OBJECTIVE: To compare the adverse event (AE)-related discontinuation rate with celecoxib vs. diclofenac when given to reduce joint pain associated with knee or hip osteoarthritis (OA) in elderly patients. METHODS: This was a double-blind, randomized, multicentre, parallel-group, 1-year comparison of celecoxib 200 mg once daily and diclofenac 50 mg twice daily in 925 patients with OA aged > or = 60 years. Study visits were at baseline and at 4, 13, 26, 39, and 52 weeks. At each visit, the Patient's and Physician's Global Assessment of Arthritis (PaGAA, PhGAA), the Patient's Assessment of Arthritis Pain--Visual Analogue Scale (PAAP-VAS), and AEs were assessed. A concomitant health economic analysis was conducted throughout. RESULTS: The rate of study discontinuation due to AEs, laboratory abnormalities, and deaths was 27% for celecoxib and 31% for diclofenac (p = 0.22). The results of the arthritis/pain efficacy assessments were similar for celecoxib and diclofenac. Significantly fewer patients in the celecoxib group than the diclofenac group experienced cardiovascular/renal AEs (70/458 vs. 95/458, p = 0.039) or hepatic AEs (10/458 vs. 39/458, p<0.0001). Medication costs were higher for celecoxib than diclofenac but mean total treatment cost was slightly higher in the diclofenac group. CONCLUSION: Treatment with celecoxib 200 mg once daily and diclofenac 50 mg twice daily resulted in similar rates of AE-related study discontinuation in elderly patients with OA. Celecoxib and diclofenac demonstrated comparable efficacy in relieving the signs and symptoms of OA. However, the proportion of patients with cardiorenal and hepatic AEs was significantly lower in the celecoxib group than the diclofenac group.

[Pharmaco-economic efficiency of the treatment of patients with acute vertebrogenic lumbar pain syndrome].

The aim of the study was to evaluate pharmaco-economic efficiency of two therapeutic schemes for the treatment of acute vertebrogenic lumbar pain syndrome. One hundred patients (including 77 women) with this syndrome caused by vertebral osteochondrosis (VO) were examined. Mean age of the patients was 41.00 +/- 8.33, mean duration of exacerbation 6.92 +/- 4.55 days. The majority of the patients had roentgenologic stage II VO. Patients of one group (n=50) were given intramuscular injections of ketorol (1 ml twice daily for 5 days) and diclofenac-retard (100 mg per os twice daily for 10 days). The second group (n=50) received ketorol and nise (100 mg twice daily for 10 days). This treatment was followed by 10 seances of phonophoresis using 1% hydrocortisone ointment. The clinical efficiency of therapy was evaluated based on the visual analog scale and in terms of Lasagne symptom, muscular syndrome index, Schober test, Thomayer's symptom, vertebrogenic syndrome coefficient. Pharmaco-economic analysis included calculation of direct medical care expenses and cost index/efficiency. The efficiency of therapy in group 2 (restoration of lumbar vertebral column mobility and alleviation of pain) was higher than in group 1 while the number of adverse effects was lower and the periods of remission longer. Combined therapy with ketorol and nise per unit efficiency was more expensive but the total cost of the management of one case including all yearly relapses suggested its advantages over the alternative treatment with ketorol and diclofenacin terms of clinical and pharmaco-economic efficiency.

Pharmacoeconomic analysis of the treatment of multiple actinic keratoses.

Actinic keratosis (AK) is common and lesions may progress to squamous cell carcinoma. The choice of therapy depends mainly on 2 factors: the efficacy of therapeutic options and the number of lesions present. Cryotherapy alone is suitable for treating a few lesions, whereas topical medications, photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), or either in combination with cryotherapy are appropriate for treating multiple (>15) lesions. When combinations are necessary, the total cost to treat multiple AKs to 100% clearance becomes important. This report provides a simple pharmacoeconomic analysis of 4 FDA-cleared therapies (imiquimod, diclofenac, 5-fluorouacil [5-FU], and ALA PDT) for AK given in combination with cryotherapy. This analysis assumes standard costs of procedures and office visits (based on April 2007 reimbursement data) and 2 treatment courses (medications: imiquimod, diclofenac, 5-FU) or sessions (ALA PDT) of each modality followed by cryotherapy to 100% clearance. The total cost of each combination is $725.17 for ALA PDT, $845.07 for diclofenac, $942.13 for 5-FU, and $1,473.39 for imiquimod. When phase III trial efficacies of the 4 modalities are considered, the actual cost of using imiquimod or diclofenac increases because additional treatments may be required. Among these 4 FDA-cleared therapies for multiple AK lesions, ALA PDT is the least expensive treatment and imiquimod is the most expensive treatment under the stated assumptions.

Costs and effects of various analgesic treatments for patients with rheumatoid arthritis and osteoarthritis in the Netherlands.

OBJECTIVE: To assess the balance between costs and upper gastrointestinal (GI) side effects of treatment with celecoxib, nonsteroidal antiinflammatory drugs (NSAIDs) alone, NSAID plus misoprostol, NSAID plus histamine-2 receptor antagonist (H(2)RA), NSAID plus proton pump inhibitor (PPI), and Arthrotec in The Netherlands. METHODS: A model was used to convene data from various sources on the probability of GI side effects and resource use. The probabilities of GI side effects for celecoxib and NSAIDs alone were derived from trial data. Calculations were based on 6 months of treatment, and were from a societal perspective. Distinction was made between low-, medium-, and high-risk patients. An extensive probabilistic sensitivity analysis was performed to address uncertainty. RESULTS: Assuming an average patient, the total costs per 6 months of therapy were: celecoxib 255 Euro, NSAIDs alone 166 Euro, NSAID plus misoprostol 285 Euro, NSAID plus H(2)RA 284 Euro, NSAID plus PPI 243 Euro, and Arthrotec 187 Euro. Treatment with celecoxib was associated with the lowest number of GI side effects and related deaths. Incremental costs per life-year saved for Arthrotec compared to NSAIDs alone were 5676 Euro for all patients and 526 Euro for medium-to-high-risk patients, whereas for high-risk patients, Arthrotec dominated NSAID alone. For celecoxib compared to Arthrotec, the incremental cost-effectiveness ratios (ICERs) were 56,667 Euro, 33,684 Euro, and 15,429 Euro, respectively. CONCLUSION: Assuming a limit of 20,000 Euro per life-year gained, from an economic point of view, Arthrotec is the preferred treatment when all patients or medium-to-high-risk patients are considered. In high-risk patients, celecoxib is the preferred treatment strategy.

Diclofenac sodium injection (Dyloject): in postoperative pain.

*A new formulation of the nonselective NSAID diclofenac sodium suitable for intravenous bolus injection has been developed using hydroxypropyl beta-cyclodextrin as a solubility enhancer (HPbetaCD diclofenac). * HPbetaCD diclofenac intravenous bolus injection was shown to be bioequivalent to the existing parenteral formulation of diclofenac containing propylene glycol and benzyl alcohol as solubilizers (PG-BA diclofenac), which is relatively insoluble and requires slow intravenous infusion over 30 minutes. * Single-dose HPbetaCD diclofenac 3.75, 9.4, 18.75, 25, 37.5, 50 and 75 mg administered by intravenous bolus injection produced significantly greater responses than placebo for total pain relief (TOTPAR) over 6 hours or pain intensity at 4 hours in the treatment of moderate or severe postoperative dental pain in randomized, double-blind trials. HPbetaCD diclofenac 37.5 and 75 mg were similar in efficacy to intravenous bolus ketorolac 30 mg. * In a well controlled trial, single-dose HPbetaCD diclofenac 75 mg intravenous bolus injection was shown to be superior to PG-BA diclofenac 75 mg intravenous infusion with respect to TOTPAR over 4 hours, indicating faster onset of analgesia in the treatment of moderate or severe postoperative dental pain. Both HPbetaCD diclofenac and PG-BA diclofenac were superior to placebo. * HPbetaCD diclofenac was generally well tolerated during single-dose treatment of postoperative pain. The tolerability profile was similar to that of PG-BA diclofenac, but with a lower incidence of thrombophlebitis.