Discovery and Development of Pregabalin (Lyrica): The Role of Public Funding.

BACKGROUND AND OBJECTIVES: Pregabalin (Lyrica), a widely used drug that has generated billions in revenue as a treatment for diabetic neuropathy and other conditions, was originally discovered in an academic medical center, largely supported by public funding. We aimed to define the extent of direct federal public funding that contributed to various stages of pregabalin's development prior to US Food and Drug Administration (FDA) approval. METHODS: We identified key research, scientists, and organizations involved in the development of pregabalin from its discovery through FDA approval. Using key terms (e.g., its indications and mechanism of action), we searched PubMed for relevant publications and determined whether each publication was based on federal public funding using the NIH RePORTER. For each award prior to the drug's FDA approval, we scored its potential relatedness to pregabalin's development based on its title, investigator, and organization, and then examined descriptions of the most relevant awards to aid in defining these relationships. The budgets for all related awards were converted to 2020 dollars. RESULTS: Pregabalin was discovered largely on the basis of publicly funded research at Northwestern University; in 1990, it was licensed to Parke-Davis, which further developed it through its FDA approval in 2004. Most key terms were related to the drug and drug target (n = 5) and organizations involved (n = 5), followed by patent-listed inventors (n = 3). These key terms linked 6,438 core project awards and we identified 37 NIH awards related to pregabalin's development: 9 awards through 1990 ($3.3 million) and 28 from 1991 through 2004 ($10.5 million). CONCLUSION: Like that of many other widely sold medications, the development of pregabalin relied on public sector as well as industry contributions to its discovery, with relevant NIH awards totaling $13.8 million during its preapproval development.

Cost-effectiveness of mirogabalin for the treatment of post-herpetic neuralgia in Taiwan.

Objectives: To assess the cost-effectiveness of mirogabalin versus no treatment or pregabalin in patients with post-herpetic neuralgia (PHN) from a third-party perspective in Taiwan.Methods: A Markov model, which was developed with 2-week cycles and 1-year time horizon from the Taiwanese National Health Insurance Administration perspective, consisted of three health states: "mild," "moderate," and "severe" pain. Average daily pain score (ADPS) was assessed at the end of each cycle. Patients either remained in, or transitioned from, their assigned health state to a different state according to their pain score changes. All patients entered the model in "moderate" (4 ≤ ADPS <7) or "severe" (7 ≤ ADPS ≤ 10) pain health states. Efficacy data was informed by the pivotal Phase III trial, or by a network meta-analysis (NMA). Utility values were obtained from published literature and cost data from Taiwanese clinical experts and the Taiwan National Health Insurance Administration, using 2018 New Taiwan dollar (NT$). Probabilistic analysis was conducted to test the robustness of base case results.Results: Head-to-head analysis showed mirogabalin 30 mg to be cost-effective versus placebo in PHN. The deterministic analysis estimated a quality-adjusted life years gain of 0.041 at an ICER of NT$11,231 (US$365) versus no treatment (ICER: NT$274,567 [US$8,900]). In the NMAs, mirogabalin was cost-effective compared to pregabalin 150 mg (ICER: NT$515,881 [US$16,720]) and 300 mg (ICER: NT$201,671 [US$6,535]). Mirogabalin 30 mg dominated pregabalin 600 mg. Results from sensitivity and scenario analyses confirmed these results.Conclusion: Mirogabalin 30 mg, a potent and selective α2δ ligand, is a cost-effective treatment option for PHN in Taiwan, with ICERs below the willingness-to-pay threshold.

Consequences on economic outcomes of generic versus brand-name drugs used in routine clinical practice: the case of treating peripheral neuropathic pain or generalized anxiety disorder with pregabalin.

BACKGROUND: Discrepancies are seen between arguments in favor of and against prescribing generic versus brand-name drugs. OBJECTIVE: To provide real-world evidence on treatment persistence, economic and clinical outcomes of pregabalin, generic versus brand-name (Lyrica®, Pfizer), routinely used to treat neuropathic pain (NP) or generalized anxiety disorder (GAD). METHODS: Electronic medical records from subjects' first starting treatment with pregabalin between January-2015 and June-2016 were analyzed. Persistence, resources utilization, and costs were assessed, along with remitter and responder rates. RESULTS: A total of 4860 records were analyzed. Discontinuation was lower with brand-name than with generic in NP (adjusted hazard ratio [HR]: 0.70 [95% CI: 0.58-0.85], p < 0.001) and GAD patients (HR: 0.63 [0.45-0.84], p < 0.001). Adjusted mean total costs were lower with brand-name: €1500 [1428-1573] vs. €2003 [1864-2143] in NP and €1528 [1322-1734] vs. €2150 [1845-2454] in GAD (both p < 0.001). More patients were remitters/ responders with brand-name in NP (55.0% vs. 46.7% and 59.2% vs. 48.4%, respectively; p < 0.001) and GAD (58.6% vs. 48.7% and 64.6% vs. 47.2%, respectively; p < 0.001). CONCLUSIONS: As a consequence of higher persistence in routine practice, patients who first started therapy with pregabalin brand-name versus generic showed better pain or anxiety outcomes at a lower cost to payers in Spain.

The clinician impact and financial cost to the NHS of litigation over pregabalin: a cohort study in English primary care.

OBJECTIVES: Following litigation over pregabalin's second-use medical patent for neuropathic pain, National Health Service (NHS) England was required by the court to instruct general practitioners (GPs) to prescribe the branded form (Lyrica) for pain. Pfizer's patent was found invalid in 2015, a ruling subject to ongoing appeals. If the Supreme Court appeal in February 2018, whose judgement is awaited, is unsuccessful, the NHS can seek to reclaim excess prescribing costs. We set out to describe the variation in prescribing of pregabalin as branded Lyrica, geographically and over time; to determine how clinicians responded to the NHS England instruction to GPs; and to model excess costs to the NHS attributable to the legal judgements. SETTING: English primary care. PARTICIPANTS: English general practices. PRIMARY AND SECONDARY OUTCOME MEASURES: Variation in prescribing of branded Lyrica across the country before and after the NHS England instruction, by practice and by Clinical Commissioning Group; excess prescribing costs. RESULTS: The proportion of pregabalin prescribed as Lyrica increased from 0.3% over 6 months before the NHS England instruction (September 2014 to February 2015) to 25.7% afterwards (April to September 2015). Although 70% of pregabalin is estimated to be for pain, including neuropathic pain, only 11.6% of practices prescribed Lyrica at this level; the median proportion prescribed as Lyrica was 8.8% (IQR 1.1%-41.9%). If pregabalin had come entirely off patent in September 2015, and Pfizer had not appealed, we estimate the NHS would have spent £502 million less on pregabalin to July 2017. CONCLUSION: NHS England instructions to GPs regarding branded prescription of pregabalin were widely ignored and have created much debate around clinical independence in prescribing. Protecting revenue from 'skinny labels' will pose a challenge. If Pfizer's final appeal on the patent is unsuccessful, the NHS can seek reimbursement of excess pregabalin prescribing costs, potentially £502 million.

Cost of treating peripheral neuropathic pain with pregabalin or gabapentin at therapeutic doses in routine practice.

AIM: To analyze the cost of peripheral neuropathic pain (PNP) treatment with pregabalin or gabapentin at therapeutic doses in routine clinical practice. METHODS: Analysis of a retrospective, observational study of electronic medical records of patients treated for PNP with therapeutic doses of pregabalin or gabapentin, with 2 years' follow-up, considering PNP type, comorbidities, concomitant analgesia and resource use. RESULTS: The weighted total average cost/patient was lower for pregabalin than gabapentin (€2464 [2197-2730] vs €3142 [2670-3614]; p = 0.014) due to significantly lower both healthcare and non-healthcare costs. This is explained by a significantly lower use of concomitant analgesia, fewer primary care visits and fewer days of sick leave. CONCLUSION: At therapeutic doses, pregabalin was found to have lower healthcare and non-healthcare costs than gabapentin in routine practice.

Healthcare Costs and Medication Adherence Among Patients with Fibromyalgia: Combination Medication vs. Duloxetine, Milnacipran, Venlafaxine, and Pregabalin Initiators.

OBJECTIVE: To examine medication adherence and healthcare costs for combination prescription initiators (duloxetine/milnacipran/venlafaxine with pregabalin) vs. monotherapy initiators (duloxetine, milnacipran, venlafaxine, and pregabalin) among patients with fibromyalgia syndrome (FMS). METHODS: Our retrospective cohort study used claims data for the South Carolina Blue Cross Blue Shield State Health Plan (SHP). Patients with FMS ≥ 18 years of age, with prescription initiation from July 1, 2007, through June 30, 2010, and SHP enrollment for 12 months pre- and post-index periods were included (combination: n = 100; pregabalin: n = 665; duloxetine: n = 713; milnacipran: n = 131; venlafaxine: n = 272). Medication adherence measures included high adherence (medication possession ratio ≥ 80%) and total supply days. Healthcare costs comprised direct medical expenditures. Propensity score methods of inverse probability of treatment weights were used to control for selection bias due to differing pre-index characteristics. RESULTS: Odds ratios for high adherence were significantly increased (P < 0.05) among the combination cohort vs. the venlafaxine (2.15), duloxetine (1.39), and pregabalin (2.20) cohorts. Rate ratios for total supply days were significantly higher (P < 0.05) for combination vs. venlafaxine (1.23), duloxetine (1.08), and pregabalin (1.32) cohorts. Expenditures for total health care were significantly higher (P < 0.05) for combination vs. duloxetine ($26,291 vs. $17,190), milnacipran ($33,638 vs. $22,886), and venlafaxine ($26,586 vs. $16,857) cohorts. CONCLUSIONS: Medication adherence was considerably better for combination prescription initiators; however, expenditures for total health care were higher. Still, our findings suggest important clinical benefits with the use of combination prescription therapy, and prospective studies of medication adherence are warranted to examine causal relationships with outcomes not captured by healthcare claims databases.

A systematic review of the effectiveness of policies restricting access to pregabalin.

BACKGROUND: Formularies often employ restriction policies to reduce pharmacy costs. Pregabalin, an alpha-2-delta ligand, is approved for treatment of fibromyalgia (FM); neuropathic pain (NeP) due to postherpetic neuralgia (PHN), diabetic peripheral neuropathy (pDPN), spinal cord injury; and as adjunct therapy for partial onset seizures. Pregabalin is endorsed as first-line therapy for these indications by several US and EU medical professional societies. However, restriction policies such as prior authorization (PA) and step therapy (ST) often favor less costly generic pain medications over pregabalin. METHODS: A structured literature search (PubMed, past 11 years) was conducted to evaluate whether restriction policies against pregabalin support real-world economic and healthcare utilization benefits. RESULTS: Search criteria identified three claims analyses and a modeling study that evaluated patients with NeP and/or FM with and without PA restrictions; three other studies included patients with FM and NeP in plans with ST requirements, and one evaluated a mail order requirement program. All studies evaluated outcomes during follow-up periods of 6 months or longer. Overall, PA, ST, and mail order restriction policies effectively reduced pregabalin usage, but the effects were inconsistent with reducing pharmacy costs and were non-significant for total disease-related medical costs. Two studies (one PA; one ST) reported significantly higher disease-related costs in restricted plans. The modeling study failed to demonstrate cost savings with PA. Opioid usage was higher in PA-restricted plans (two studies). The US Centers for Disease Control and Prevention and several professional NeP guidelines recommend opioid use only in cases when other non-opioid pain therapies have proven ineffective. New US Government taskforce guidelines now seek to reduce opioid exposure. Additionally, in both ST studies, gabapentin utilization (a common ST edit) was significantly increased. Both studies had substantial proportions of FM and pDPN patients and the only pain condition gabapentin is approved to treat in the United States is PHN. CONCLUSION: PA and ST restriction policies significantly decrease utilization of pregabalin, but do not consistently demonstrate cost savings for US health plans. More research is needed to evaluate whether these policies may lead to increased opioid usage as found in some studies. TRIAL REGISTRATION: N/A.

Treatment patterns of postherpetic neuralgia patients before and after the launch of pregabalin and its effect on medical costs: Analysis of Japanese claims data provided by Japan Medical Data Center.

Except for neurotrophin, no drug had an indication for postherpetic neuralgia (PHN) in Japan prior to pregabalin approval. This approval might have changed PHN treatment patterns. This study aimed to compare PHN treatment patterns and medical costs between patients who started treatment before and after pregabalin approval. Japanese claims data were used to identify patients aged 18 years or more with PHN, postherpetic trigeminal neuralgia or postherpetic polyneuropathy who were initiated on their first PHN-associated prescription through May 2010 (before approval) or from June 2010 (after approval). From these claims, 6-month treatment patterns from first prescription were compared for the periods before and after approval. These patterns included pain-related medications and the frequency of pain-relief procedures. All-cause and pain-related medical costs were also compared for these periods. The number of PHN patients who were initiated on treatment before and after approval were 107 (mean age, 47.4 ± 13.0 years) and 505 (45.9 ± 13.0), respectively. Post-approval, significant reductions were observed for prescription of non-steroidal anti-inflammatory drugs, tricyclic antidepressants and neurotrophin relative to before approval. Excluding pregabalin acquisition costs, mean costs per patient for medications associated with PHN for 6 months from the first prescription were significantly lower after approval, ¥2882 vs ¥4185. Total medical costs were similar in both periods. Approval of pregabalin appeared to result in a treatment paradigm toward use of an approved therapy with demonstrated efficacy.

Cost-Utility of Group Acceptance and Commitment Therapy for Fibromyalgia Versus Recommended Drugs: An Economic Analysis Alongside a 6-Month Randomized Controlled Trial Conducted in Spain (EFFIGACT Study).

The aim of this study was to analyze the cost utility of a group-based form of acceptance and commitment therapy (GACT) in patients with fibromyalgia (FM) compared with patients receiving recommended pharmacological treatment (RPT) or on a waiting list (WL). The data were derived from a previously published study, a randomized controlled trial that focused on clinical outcomes. Health economic outcomes included health-related quality of life and health care use at baseline and at 6-month follow-up using the EuroQoL and the Client Service Receipt Inventory, respectively. Analyses included quality-adjusted life years, direct and indirect cost differences, and incremental cost effectiveness ratios. A total of 156 FM patients were randomized (51 GACT, 52 RPT, 53 WL). GACT was related to significantly less direct costs over the 6-month study period compared with both control arms (GACT €824.2 ± 1,062.7 vs RPT €1,730.7 ± 1,656.8 vs WL €2,462.7 ± 2,822.0). Lower direct costs for GACT compared with RPT were due to lower costs from primary care visits and FM-related medications. The incremental cost effectiveness ratios were dominant in the completers' analysis and remained robust in the sensitivity analyses. In conclusion, acceptance and commitment therapy appears to be a cost-effective treatment compared with RPT in patients with FM. PERSPECTIVE: Decision-makers have to prioritize their budget on the treatment option that is the most cost effective for the management of a specific patient group. From government as well as health care perspectives, this study shows that a GACT is more cost effective than pharmacological treatment in management of FM.

A study on comparative efficacy and cost effectiveness of Pregabalin and Duloxetine used in diabetic neuropathic pain.

AIM: The study was designed for comparing the efficacy and cost effectiveness of Pregabalin and Duloxetine used in Diabetic Neuropathic Pain. METHODS: The prospective interventional 6 month study was conducted in a diabetic clinic of a 500 bedded tertiary care hospital in South India. The subjects having diagnosed with diabetic neuropathy and not treated with Pregabalin and Duloxetine or any other drugs of its class were selected. The data were collected using NPS and Neuro QoL questionnaires. The cost of both drugs used in the study was calculated as the mean of the price of 3 leading common brands of those drugs. The comparative efficacy was calculated by comparing the mean difference produced by both drugs in NPS and QoL scores. The cost effectiveness were calculated by ICER ratio. RESULTS: The results have shown a significant improvement in the mean difference of NPS and Neuro QoL scores of both Pregabalin (p=<0.001) and Duloxetine (p=<0.001) before and after the therapy, the Duloxetine dominates over Pregabalin in both. The mean cost of Pregabalin for 3 months therapy was found to be INR 668.7 and that for Duloxetine was INR 756. Duloxetine showed a better effect but more expensive. ICER ratio was calculated and found that a cost of INR 61.47 per extra QoL gained by Duloxetine. CONCLUSION: The study have revealed that, both drugs are found to be effective.On conducting cost effective analysis, a significant better improvement in QoL of patients was obtained by Duloxetine with comparatively mild increase in the price.

Cost of treatment of peripheral neuropathic pain with pregabalin or gabapentin in routine clinical practice: impact of their loss of exclusivity.

To analyze the effect of loss of exclusivity of data on the cost of treatment of peripheral neuropathic pain (PNP) with pregabalin or gabapentin in routine clinical practice. A retrospective observational study, with electronic medical records for patients enrolled at primary care centers managed by the health care provider Badalona Serveis Assistencials, who initiated treatment of PNP with pregabalin or gabapentin. The analysis used drugs and resources prices for year 2015. The 1163 electronic medical records (pregabalin; N = 764, gabapentin; N = 399) for patients (62.2% women) with a mean (standard deviation) age of 59.2 (14.7) years were analyzed. Treatment duration was slightly shorter with pregabalin than with gabapentin (5.2 vs 5.5 months; P = 0.124), with mean doses of 227.4 (178.6) mg and 900.0 (443.4) mg, respectively. The average study drug cost per patient was higher for pregabalin than for gabapentin; €214.6 (206.3) vs €157.4 (181.9), P < 0.001, although the cost of concomitant analgesic medication was lower; €176.5 (271.8) vs €306.7 (529.2), P < 0.001. The adjusted average total cost per patient was lower in those treated with pregabalin than in those treated with gabapentin; €2,413 (2119-2708) vs €3201 (2806-3.597); P = 0.002, owing to significantly lower health care costs; €1307 (1247-1367) vs €1538 (1458-1618), P < 0.001, and also non-health care costs; €1106 (819-1393) vs €1663 (1279-2048), P = 0.023, that was caused by a significantly lower use of concomitant medication, fewer medical visits to primary care, and fewer days of sick leave. After loss of exclusivity of both drugs, pregabalin continued to show lower health care and non-health care costs than gabapentin in the treatment of PNP in routine clinical practice.

Impact of a Novel Cost-Saving Pharmacy Program on Pregabalin Use and Health Care Costs.

BACKGROUND: Pharmacy cost-saving programs often aim to reduce costs for members and payers by encouraging use of lower-tier or generic medications and lower-cost sales channels. In 2010, a national U.S. health plan began a novel pharmacy program directed at reducing pharmacy expenditures for targeted medications, including pregabalin. The program provided multiple options to avoid higher cost sharing: use mail order pharmacy or switch to a lower-cost alternative medication via mail order or retail. Members who did not choose any option eventually paid the full retail cost of pregabalin. OBJECTIVE: To evaluate the impact of the pharmacy program on pregabalin and alternative medication use, health care costs, and health care utilization. METHODS: This retrospective analysis of claims data included adult commercial health plan members with a retail claim for pregabalin in the first 13 months of the pharmacy program (identification [ID] period: February 1, 2010-February 28, 2011). Members whose benefit plan included the pharmacy program were assigned to the program cohort; all others were assigned to the nonprogram cohort. The program cohort index date was the first retail pregabalin claim during the ID period and after the program start; the nonprogram cohort index date was the first retail pregabalin claim during the ID period. All members were continuously enrolled for 12 months pre- and post-index and had at least 1 inpatient claim or ≥ 2 ambulatory visit claims for a pregabalin-indicated condition. Cohorts were propensity score matched (PSM) 1:1 with logistic regression on demographic and pre-index characteristics, including mail order and pregabalin use, comorbidity, health care costs, and health care utilization. Pregabalin, gabapentin and other alternative medication use, health care costs, and health care utilization were measured. The program cohort was also divided into 2 groups: members who changed to gabapentin post-index and those who did not. A difference-in-differences (DiD) analysis was used to compare the between-cohort change in pregabalin and alternative medication use patterns, health care costs, and health care resource utilization from pre- to post-index. The within-cohort change from pre- to post-index was analyzed by McNemar's test (categorical variables) or paired t-test (continuous variables). The Rao-Scott chi-square test (categorical) and general estimating equations (continuous) were used to analyze between-cohort differences at each time point. Differences in program member characteristics of those who changed versus those who did not change to gabapentin post-index were assessed by traditional chi-square test (categorical) or two-sample t-test (continuous variables). RESULTS: A total of 1,218 members in each cohort were PSM. Mean age was 51 years, 76.7% were women, and the most common pregabalin-indicated condition was fibromyalgia (77.6%). After the program start, the mean number of pregabalin claims from mail order and retail combined decreased in the program cohort from 4.7 pre-index to 3.8 post-index, and increased in the nonprogram cohort from 4.7 pre-index to 6.2 post-index (DiD, P < 0.001). Pregabalin mail order use increased from 3.1% to 48.1% of program members versus 2.8% to 9.4% of nonprogram members (DiD, P < 0.001). Program members were also more likely to change to the anticonvulsant gabapentin post-index than were nonprogram members (31.0% vs. 15.9%, P < 0.001). Mean total health care costs were similar between cohorts, and the pre- to post-index change did not differ between cohorts (DiD, P = 0.474). However, mean total pharmacy costs rose from pre-index to post-index by $820 and $790 in the program and nonprogram cohorts, respectively (both P < 0.001); the increase was similar between cohorts (DiD, P = 0.888). Program members who changed to gabapentin had a higher mean comorbidity score (P = 0.001) and greater post-index use of opioids, alternative medications, and health care resources (P < 0.050) than program members who did not change to gabapentin. CONCLUSIONS: The pharmacy program increased mail order use of pregabalin but reduced pregabalin claims from any venue. Program members were more likely to change to gabapentin than were nonprogram members, and those who changed had higher comorbidity, use of alternative medication, and health care resources. Despite increased mail order use for pregabalin and greater change to gabapentin by program members, the pharmacy program was not cost saving with respect to mean pharmacy or total health care costs.

Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the probability of capsaicin 8% patch being cost-effective versus pregabalin was 97%. Capsaicin 8% patch is a cost-effective treatment option compared with dose-optimized pregabalin in patients with PNP who have failed one or more previous systemic treatments.

Long-term cost-effectiveness of initiating treatment for painful diabetic neuropathy with pregabalin, duloxetine, gabapentin, or desipramine.

Painful diabetic neuropathy (PDN) affects nearly half of patients with diabetes. The objective of this study was to compare the cost-effectiveness of starting patients with PDN on pregabalin (PRE), duloxetine (DUL), gabapentin (GABA), or desipramine (DES) over a 10-year time horizon from the perspective of third-party payers in the United States. A Markov model was used to compare the costs (2013 $US) and effectiveness (quality-adjusted life-years [QALYs]) of first-line PDN treatments in 10,000 patients using microsimulation. Costs and QALYs were discounted at 3% annually. Probabilities and utilities were derived from the published literature. Costs were average wholesale price for drugs and national estimates for office visits and hospitalizations. One-way and probabilistic (PSA) sensitivity analyses were used to examine parameter uncertainty. Starting with PRE was dominated by DUL as DUL cost less and was more effective. Starting with GABA was extendedly dominated by a combination of DES and DUL. DES and DUL cost $23,468 and $25,979, while yielding 3.05 and 3.16 QALYs, respectively. The incremental cost-effectiveness ratio for DUL compared with DES was $22,867/QALY gained. One-way sensitivity analysis showed that the model was most sensitive to the adherence threshold and utility for mild pain. PSA showed that, at a willingness-to-pay (WTP) of $50,000/QALY, DUL was the most cost-effective option in 56.3% of the simulations, DES in 29.2%, GABA in 14.4%, and PRE in 0.1%. Starting with DUL is the most cost-effective option for PDN when WTP is greater than $22,867/QALY. Decision makers may consider starting with DUL for PDN patients.

Duloxetine for the treatment of painful diabetic peripheral neuropathy in Venezuela: economic evaluation.

INTRODUCTION: Painful diabetic peripheral neuropathy affects 40-50% of patients with diabetic neuropathy, leading to impaired quality of life and substantial costs. Duloxetine and pregabalin have evidence-based support, and are formally approved for controlling painful diabetic peripheral neuropathy. METHODS: We used a 12-week decision model for examining painful diabetic peripheral neuropathy first-line therapy with daily doses of duloxetine 60mg or pregabalin 300mg, under the perspective of the Instituto Venezolano de los Seguros Sociales. We gathered model parameters from published literature and expert´s opinion, focusing on the magnitude of pain relief, the presence of adverse events, the possibility of withdrawal owing to intolerable adverse events or due to lack of efficacy, and the quality-adjusted life years expected in each strategy. We analyzed direct medical costs (which are expressed in Bolívares Fuertes, BsF) comprising drug acquisition besides additional care devoted to treatment of adverse events and poor pain relief. We conducted both deterministic and probabilistic sensitivity analyses. RESULTS: Total expected costs per 1000 patients were BsF 1 046 146 (26%) lower with duloxetine than with pregabalin. Most of these savings (91%) corresponds to the difference in the acquisition’s cost of each medication. duloxetine also provided 23 more patients achieving good pain relief and a gain of about two quality-adjusted life years per 1000 treated. Model was robust to plausible changes in main parameters. Duloxetine remained the preferred option in 93.9% of the second-order Monte Carlo simulations. CONCLUSIONS: This study suggests duloxetine dominates (i.e., is more effective and lead to gains in quality-adjusted life years), remaining less costly than pregabalin for treatment of painful diabetic peripheral neuropathy.

INTRODUCCIÓN : La neuropatía diabética periférica dolorosa (NDPD) afecta a 40-50% de los pacientes con neuropatía diabética y se asocia con un deterioro significativo de la calidad de vida y con costos de magnitud considerable. Tanto duloxetina (DUL) como pregabalina (PGB) cuentan con sustento científico basado en evidencias y han sido formalmente aprobados para controlar la NDPD. MÉTODOS: Se utilizó un modelo de decisión a 12 semanas para examinar el tratamiento de primera línea para la neuropatía diabética periférica dolorosa, con dosis diarias de duloxetina 60 mg o con pregabalina 300 mg, bajo la perspectiva del Instituto Venezolano de los Seguros Sociales. Los parámetros del modelo proceden de literatura publicada y opinión de expertos, enfocándose en la magnitud del alivio del dolor, la presencia de eventos adversos, la posibilidad de abandono debido a eventos adversos intolerables o por falta de eficacia y en los años de vida ajustados por calidad esperados con cada estrategia. Se analizaron los costos médicos directos (expresados en bolívares fuertes), integrados por la adquisición de medicamentos, además del cuidado adicional que se origina por el tratamiento de los eventos adversos y como consecuencia de un pobre alivio del dolor. Se llevaron a cabo análisis de sensibilidad de tipo determinístico y probabilístico. RESULTADOS: Los costos totales esperados por cada 1000 pacientes fueron de 1 046 146 bolívares fuertes (26%) más bajos con duloxetina en comparación con la pregabalina. La mayor parte de estos ahorros (91%), corresponde a la diferencia en el costo de adquisición entre ambos medicamentos. La duloxetina también se asoció con ganancias de 23 pacientes que lograron un buen alivio del dolor y de dos años de vida ajustados por calidad por cada 1000 tratados. El modelo se mantuvo robusto ante cambios plausibles en sus parámetros principales. La duloxetina continuó siendo la opción preferida en 93,9% de las simulaciones de Monte Carlo de segundo orden generadas. CONCLUSIONES: El presente estudio sugiere que la duloxetina domina a (es más efectiva, conduce a ganancias en años de vida ajustados por calidad y es menos costosa que) la pregabalina, para el tratamiento de la neuropatía diabética periférica dolorosa.

Conversion from thrice- to twice-daily pregabalin dosing for pain: Economic and clinical outcomes in a veteran population.

PURPOSE: Results of a study analyzing economic and clinical outcomes one year after conversion from thrice- to twice-daily pregabalin dosing for pain are presented. METHODS: A retrospective chart review was conducted at two Veterans Affairs facilities. The analyzed population included all patients receiving pregabalin for pain whose dosing was converted from thrice- to twice-daily pregabalin dosing during a one-year period. The primary endpoint was the economic impact of the conversion. Secondary endpoints included reversion to thrice-daily pregabalin dosing, pregabalin discontinuation, addition of medications for pain, and unscheduled neuropathy-related visits. RESULTS: Among the 57 patients included in the data analysis, 41 continued to take pregabalin twice daily, 10 had pregabalin discontinued, and 6 had dosing reverted to thrice daily. The mean age of patients and the distribution of add-on pain medications did not differ significantly between patients whose pregabalin dosing frequency remained at twice daily and patients whose frequency reverted to thrice daily. The costs associated with pregabalin therapy differed significantly between the preconversion and postconversion periods. A savings of $115,867 was realized from this conversion for both facilities combined over the course of one year. CONCLUSION: In patients receiving pregabalin for pain, conversion from thrice- to twice-daily pregabalin dosing-while maintaining the same daily dose-resulted in substantial cost savings while having little effect on clinical outcomes.

A retrospective, matched cohort study of potential drug-drug interaction prevalence and opioid utilization in a diabetic peripheral neuropathy population initiated on pregabalin or duloxetine.

BACKGROUND: Anticipating and controlling drug-drug interactions (DDIs) in older patients with painful diabetic peripheral neuropaty (pDPN) presents a significant challenge to providers. The purpose of this study was to examine the impact of newly initiated pregabalin or duloxetine treatment on Medicare Advantage Prescription Drug (MAPD) plan pDPN patients' encounters with potential drug-drug interactions, the healthcare cost and utilization consequences of those interactions, and opioid utilization. METHODS: Study subjects required a pregabalin or duloxetine pharmacy claim between 07/01/2008-06/30/2012 (index event), ≥1 inpatient or ≥2 outpatient medical claims with pDPN diagnosis between 01/01/2008-12/31/2012, and ≥12 months pre- and ≥6 post-index enrollment. Propensity score matching was used to balance the pregabalin and duloxetine cohorts on pre-index demographics and comorbidities. Potential DDIs were defined by Micromedex 2.0 and identified by prescription claims. Six-month post-index healthcare utilization (HCU) and costs were calculated using pharmacy and medical claims. RESULTS: No significant differences in pre-index demographics or comorbidities were found between pregabalin subjects (n = 446) and duloxetine subjects (n = 446). Potential DDI prevalence was significantly greater (p < 0.0001) among duoxetine subjects (56.7%) than among pregabalin subjects (2.9%). There were no significant differences in HCU or costs between pregablin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($13,908 vs. $9,830; p = 0.001), more subjects with ≥1 inpatient visits (35.6% vs 25.4%; p = 0.02), and more subjects with ≥1 emergency room visits (32.8% vs. 20.7%; p = 0.005) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a difference between pregabalin and duloxetine subjects in their respective pre-versus-post differences in milligrams (mg) of morphine equivalents/30 days used (60.2 mg and 176.9 mg, respectively; p = 0.058). CONCLUSION: The significantly higher prevalence of potential DDIs and potential cost impact found in pDPN duloxetine users, relative to pregabalin users, underscore the importance of considering DDIs when selecting a treatment.