Efficacy and expenses of succimer vs. d-penicillamine plus garlic in the treatment of lead poisoning: a retrospective cross-sectional study.

PURPOSE: Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning. METHODS: In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens. RESULTS: Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients. CONCLUSION: Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.

Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson's disease in resource constrained setting.

BACKGROUND: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. AIM: To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. METHODS: We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child's, model for end-stage liver disease (MELD), Nazer's, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points-baseline at presentation, at transition from penicillamine to zinc and at end of follow up. RESULTS: Thirty-one patients (median age 11 [5-24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child's class A, five to Child's B, and 17 to Child's C. Duration of initial penicillamine chelation therapy was 134 (2-320) weeks, and of subsequent zinc therapy was 363 (35-728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child's, MELD, Nazer's, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2-20) years. Fifteen of the 17 Child's C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up. CONCLUSIONS: Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

Withdrawal of penicillamine from zinc sulphate-penicillamine maintenance therapy in Wilson's disease: promising, safe and cheap.

BACKGROUND: Penicillamine, once considered the cornerstone of treatment for Wilson disease (WD), is rather expensive and toxic, and often causes neurological worsening. Zinc sulphate, aiming at the treatment of free-copper toxicosis, has emerged as effective, safe and cheap alternative. AIM: To assess the effect of withdrawal of penicillamine from maintenance treatment with penicillamine and zinc sulphate. PATIENTS AND METHODS: 45 patients of WD (M:F: 28:17; age at diagnosis: 13.5+/-63 years), on both penicillamine (P) and zinc sulphate (Zn), couldn't continue penicillamine due to financial constraints. Their clinical data, disability and impairment scores (Schwab and England (S&E) score, Neurological Symptom Score (NSS), and Chu staging) and follow-up data of patients maintained only on zinc sulphate were recorded. RESULTS: Majority of patients (84.4%) had neuropsychiatric manifestations. The mean duration of treatment with penicillamine (P) and zinc sulphate (P+Zn), before stopping penicillamine, was 107.4+/-67.3 months. 40 patients improved variably, while the rest didn't. They received only zinc sulphate for 27.2+/-8.5 months (range: 12 to 34) and 44 patients (97.7%) remained status quo or improved marginally. Only one patient reported worsening in dysarthria. Their disability and impairment scores during combination (penicillamine and zinc sulphate) and Zn alone were: Chu (1.3+/-0.5 vs. 1.5+/-1.9; p=0.4), NSS (1.8+/-3.1 vs. 1.5+/-2.3; p=0.03) and S&E (96.4+/-5.6 vs. 98.6+/-3.5; p=0.03). There were no adverse effects. CONCLUSIONS: Withdrawal of penicillamine from zinc sulphate/penicillamine maintenance therapy for patients with Wilson's disease was effective, safe and economic, for almost all patients. This retrospective study reiterates that zinc sulphate may be used as a preferred mode of treatment for patients with Wilson's disease.

A cost effectiveness analysis of cyclosporine in rheumatoid arthritis.

OBJECTIVE: To perform a cost effectiveness analysis of cyclosporine (CyA) in the treatment of rheumatoid arthritis (RA). METHODS: Five randomized controlled parallel group clinical trials were selected for metaanalysis. A fixed effects model was used to calculate the treatment effects among the studies. An incremental economic analysis was performed from both a societal perspective and the perspective of Ontario Ministry of Health (MOH). A placebo comparison and 2 head to head comparisons were performed. The total treatment cost was calculated for a typical patient based on a modified intent to treat approach modelled over a one year period. RESULTS: CyA produced a 25% or greater improvement in tender joint account in 35% of the patients relative to 17% of patients receiving placebo. There was no significant difference in improvement between CyA and azathioprine (Aza) or D-penicillamine (D-Pen). From the perspective of the Ontario MOH, the annual incremental cost of achieving the same level of improvement between CyA and Aza was found to be $1,473, and between CyA and D-Pen, $1,618; the annual incremental cost effectiveness ratio per patient improved of adopting CyA over placebo was $11,547. From a societal perspective, the incremental cost of CyA was $2,886 and $3,731 between Aza and D-Pen, respectively. The annual incremental cost effectiveness ratio against placebo was $20,698. CONCLUSION: Given budgetary constraints on provincial drug plans, guidelines identifying patients in whom the cost effectiveness of CyA may be expected to be most favorable need to be explored. When CyA is the last option available to alleviate RA, whether it is "good value for money" depends upon the importance placed on patient improvement by the patients and/or by society, and on the alternative uses of the same scarce resources.

The total costs of drug therapy for rheumatoid arthritis. A model based on costs of drug, monitoring, and toxicity.

OBJECTIVE: We created a model to estimate the total medication costs of treating patients with rheumatoid arthritis with 6 second-line agents for the first 6 months of treatment. METHODS: Drug costs were obtained from a survey of pharmacies; monitoring costs were calculated from utilization information obtained in a survey of rheumatologists; toxicity costs were obtained using decision trees to represent the evaluation and treatment of potential toxicities. Monitoring and toxicity costs were estimated using costs from the Boston University Medical Center or, for hospitalizations, using appropriate diagnosis-related group categories. The sum of the 3 components determined the total medication costs. RESULTS: The least expensive medication was penicillamine, at $10.62/week, and the most expensive was injectable gold, at $30.89/week. In terms of monitoring costs, methotrexate had the highest costs associated with necessary laboratory tests and office visits. Hydroxychloroquine had the lowest monitoring costs for office visits, and oral gold had the lowest for laboratory costs. Hematologic toxicities were the largest component of toxicity costs for all 6 medications, and renal toxicities were costly for patients taking oral gold, penicillamine, and injectable gold. Total medication costs revealed oral gold as the least expensive medication and injectable gold as the most expensive. The combination of monitoring and toxicity costs accounted for more than 60% of the total costs for all medications except injectable gold. In all cases, the cost of treating toxicities was the smallest of the 3 components. CONCLUSION: When calculating the costs of drug therapy, it is important to consider not only the price of the drug, but also the costs of monitoring and treating the toxicities that might occur. Failure to do so will result in underestimating the true costs of treatment with these medications.

Management of childhood lead poisoning: clinical impact and cost-effectiveness.

OBJECTIVES: No consensus exists regarding the preferred treatment of childhood lead poisoning. The authors used decision analysis to compare the clinical impacts and cost-effectiveness of four management strategies for childhood lead poisoning, and to investigate how effective chelation therapy must be in reducing neuropsychologic sequelae to warrant its use. METHODS: The model was based on a 2-year-old child with moderate lead poisoning [blood lead level 1.21 to 1.88 mumol/L (25 to 39 micrograms/dL)]. The following strategies were compared: 1) no treatment; 2) EDTA provocation testing, followed by chelation if testing is positive (PROV); 3) penicillamine chelation with crossover to EDTA provocation testing if toxicity occurs (PCA); 4) EDTA provocation testing with crossover to penicillamine chelation if testing is negative (EDTA). RESULTS: The EDTA and PCA strategies prevented 22.5% of the cases of reading disability and resulted in an increase of 1.02 quality-adjusted life years compared with no treatment. When the costs of outpatient EDTA testing and chelation are considered, the EDTA strategy is more cost-effective than the PCA strategy; when inpatient costs are considered, the PCA strategy becomes more cost-effective. When costs of remedial education are considered, all strategies are cost-saving compared with no treatment if chelation reduces the risk of lead-induced reading disability by more than 20%. CONCLUSIONS: Treatment strategies for childhood lead poisoning vary in clinical impact, cost, and cost-effectiveness. Chelation of the 1.4% of United States preschoolers whose blood lead levels are 2.21 mumol/L (25 micrograms/dL) or higher could prevent more than 45,000 cases of reading disability, and save more than $900 million per year in overall costs when the costs of remedial education are considered.