Cost effectiveness of rituximab and mycophenolate mofetil for neuromyelitis optica spectrum disorder in Thailand: Economic evaluation and budget impact analysis.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory condition of the central nervous system. The extent of disability depends on the severity of the disease and the number of relapses. Although azathioprine is currently the main treatment for patients with NMOSD in Thailand, patients often relapse during its use. Hence, it is argued that there are other drugs that would be more effective. The purpose of this study is to evaluate, from a societal perspective and from the economic impact on Thailand's healthcare system, the cost utility of treatment with mycophenolate mofetil (MMF) and rituximab in patients resistant to azathioprine. The Markov model with a one-year cycle length was applied to predict the health and cost outcomes in patients with NMOSD over a lifetime. The results showed that rituximab exhibited the highest quality-adjusted life year (QALY) gains among all the options. Among the rituximab-based treatments, the administration of a rituximab biosimilar with CD27+ memory B cell monitoring proved to be the most cost-effective option. At the willingness-to-pay threshold of 160,000 Thai baht (THB), or 5,289 US dollar (USD), per QALY gained, the treatment exhibited the highest probability of being cost effective (48%). A sensitivity analysis based on the adjusted price of a generic MMF determined that the treatment was cost effective, exhibiting an incremental cost-effectiveness ratio of -164,653 THB (-5,443 USD) and a 32% probability of being cost effective. The calculated budget impact of treating patients resistant to conventional therapy was 1-6 million THB (33,000-198,000 USD) for the first three years, while after the third year, the budget impact stabilized at 3-4 million THB (99,000-132,000 USD). These data indicate that, in Thailand, treatment of drug resistant NMOSD with a rituximab biosimilar with CD27+ memory B cell monitoring or treatment with a generic MMF would be cost effective and would result in a low budget impact. Therefore, the inclusion of both the rituximab biosimilar and a generic MMF in the National Drug List of Essential Medicine for the treatment of NMOSD may be appropriate.

Cost-effectiveness of tacrolimus for the treatment of moderate-to-severe lupus nephritis in China.

Aim: Therapy for lupus nephritis (LN) requires treatment with immunosuppressive regimens, often including intravenous cyclophosphamide (IVCY), mycophenolate mofetil (MMF) or azathioprine. Additionally, tacrolimus (original form or generic) is recommended to treat LN patients in Asia, including China. However, the cost-effectiveness of tacrolimus therapy has not previously been assessed. We aimed to estimate the cost-effectiveness of tacrolimus in the treatment of moderate-to-severe LN versus standard therapies in China. Materials & methods: This cost-effectiveness model combined a decision-tree/Markov-model structure to map transitions between health states during induction and maintenance treatment phases. Induction with tacrolimus, IVCY or MMF, was followed by tacrolimus, MMF or azathioprine maintenance. Results: According to the model, during induction, complete remission rates were higher with tacrolimus versus IVCY (relative risk 1.40 vs IVCY [deterministic sensitivity analysis minimum 0.92, maximum 2.13]) and time to response was shorter. Relapse rates were lower with tacrolimus versus azathioprine or MMF during maintenance. Tacrolimus induction and maintenance was the most cost-effective regimen, incurring the lowest total costs (CN¥180,448) with the highest quality-adjusted life-years. Conclusion: The model demonstrated that tacrolimus use in both induction and maintenance therapy may be an efficacious and cost-effective treatment for LN in China.

Refill-Based Medication Use Quality Measures in Kidney Transplant Recipients: Examination of Proportion of Days Covered and Medication Possession Ratio.

BACKGROUND: The Pharmacy Quality Alliance's definition of proportion of days covered (PDC) and medication possession ratio (MPR) have not been examined as potential quality measures in the kidney transplant recipient population. OBJECTIVES: To (a) describe the frequency distribution of MPR and PDC using mycophenolic acid products in a real-world kidney transplant recipient population and (b) evaluate associations between MPR and PDC with late (> 90 days after transplantation) biopsy-proven acute rejection (BPAR). METHODS: This was a retrospective cohort study combining data from the Wisconsin Allograft Recipient Database with University of Wisconsin (UW) Health Specialty Pharmacy prescription claims and dispensing data from March 10, 2006, to June 30, 2012. Patients who met criteria for persistence filling mycophenolic acid prescriptions at UW Health Specialty Pharmacy in the first year following discharge from kidney transplantation surgery hospitalization were included. Patients were excluded if they were enrolled in a clinical trial, if they had BPAR within 90 days of transplantation, or if they did not have panel reactive antibody data available. PDC and MPR were calculated over 360 days after discharge, and multivariable analyses were performed to determine if there were associations between PDC or MPR with late BPAR within 3 years. RESULTS: This study included 388 patients. The incidence of 3-year late BPAR was 5.1% (n = 20). Characteristics of patients who experienced late BPAR were largely consistent with those who did not experience late BPAR, with the exception of number of hospital readmissions, which was higher among patients who experienced late BPAR. The frequency distribution of PDC and MPR exhibited a skewed left distribution, with a median PDC of 0.972 and a median MPR of 1.000. Higher PDC was associated with lower odds of late BPAR (OR = 0.041, 95% CI = 0.004-0.417) in multivariable analysis, as was a higher MPR (OR = 0.041, 95% CI = 0.004-0.419). CONCLUSIONS: MPR and PDC may be calculated from data available to pharmacies and health plans, and each was associated with 3-year late BPAR among patients who did not experience early BPAR. However, the construct validity of these medication adherence measures requires further study. DISCLOSURES: This study was not funded. The authors report no conflicts of interest and no relevant financial interests related to the products or services discussed in this article. Study concept and design were contributed by Hofmeyer, along with Look and Hager. Hager took the lead in data collection, along with the other authors. Data interpretation was performed by Look, along with the other authors. The manuscript was primarily written by Hofmeyer, assisted by Look and Hager, and revised by all of the authors.

Cost-Effectiveness Analysis of Everolimus versus Mycophenolate in Kidney Transplant Recipients Receiving No Pharmacological Prophylaxis for Cytomegalovirus Infection: A Short-Term Pharmacoeconomic Evaluation (12 Months).

BACKGROUND: Modern immunosuppressive regimens, although associated with improved 1-year graft survival, are associated with adverse effects, including opportunistic infections, diabetes mellitus after transplantation, cardiovascular complications, and de novo malignancies. OBJECTIVES: To determine the short-term (12 months) cost-effectiveness of everolimus (EVR) versus mycophenolate sodium (MPS) in kidney transplant recipients receiving induction therapy, tacrolimus, prednisone, and no prophylaxis for cytomegalovirus infection. METHODS: A Markov state transition model was designed. Data from a single-center prospective trial were used along with data from the center's medical bills database. The target population comprised adults with low immunological risk submitted to first ABO-compatible transplantation with kidneys recovered from living or deceased donors. The time horizon was 12 months. The interventions included tacrolimus and prednisone plus a single 3-mg/kg dose of rabbit antithymocyte globulin (ATG) and EVR or basiliximab (BAS) and EVR or BAS and MPS. The clinical outcomes considered for this analysis were cytomegalovirus infection/disease, acute rejection, graft dysfunction, surgical complications, graft loss, and life-years gained. RESULTS: ATG/EVR was cost-saving compared with BAS/MPS on all evaluated outcomes; BAS/EVR outperformed BAS/MPS on most of the evaluated outcomes. Results were confirmed by sensitivity analysis. CONCLUSIONS: Compared with MPS, EVR is an alternative immunosuppressive agent that is able to provide resource-saving to the health care provider with effectiveness gains for the patient.

Mycophenolate mofetil or cyclophosphamide in indian patients with lupus nephritis: Which is better? A single-center experience.

Mycophenolate mofetil (MMF) is used extensively for the induction therapy of lupus nephritis (LN) and has even outpaced intravenous (i.v.) cyclophosphamide (CyP) as the initial choice of therapy. There are no studies comparing the response of MMF with standard dose i.v. CyP in Indian patients with LN. We conducted a 24-week prospective, randomized, open-label trial comparing oral MMF with monthly i.v. CyP as induction therapy for active biopsy proven Class III and IV LN. The primary end-point was response to treatment at 24 weeks, and the secondary end-points were complete remission, Systemic Lupus Erythematosus Disease Activity Index scores (SLEDAI) and adverse reactions. Of the 40 patients, 17 were randomized to the MMF group and 23 to the i.v. CyP group. Complete remission was seen in nine (52.94%) patients in the MMF group and 11 (47.82%) in the i.v. CyP group. Partial remission was seen in six (35.30%) in the MMF group and nine (39.13%) in the i.v. CyP group. At six months, the cumulative probability of response was not statistically significant between the two groups (P = 1.000). MMF is comparable to i.v. CyP in the management of LN in Indian patients having an equal safety profile. The dose of MMF required was lower than the conventional doses used in other studies suggesting genetic or environmental factors in the Indian population influencing the metabolism of MMF, which requires further evaluation. The cost of MMF is a limiting factor in its use. The use of i.v. CyP is favorable as the monthly doses ensure compliance and is also cost-effective.

Efficacy and Safety of Generic Mycophenolate Mofetil (My-rept) 500-Milligram Tablets in Primary Liver Transplant Recipients.

BACKGROUND: Generic immunosuppressants may be cost-effective if clinical outcomes are equivalent to the brand-name medications. Mycophenolate mofetil in the form of My-rept may be cost-effective being a generic immunosuppressant, which is available as a 500-mg tablet as well as a 250-mg capsule (Chong Kun Dang Pharmaceutical Corporation, Seoul, Korea). OBJECTIVE: This study aimed to evaluate the efficacy, safety, cost-effectiveness, and convenience of My-rept 500-mg tablets in liver transplant recipients. SETTING: The setting was an outpatient liver transplantation clinic of a tertiary hospital in Korea. METHOD: A phase 4, single-center, open-label, noncomparative study was undertaken. A total of 50 patients were recruited. Acute transplant rejection, changes in blood chemistry, white blood cell count, assessments of renal function, occurrence of adverse drug reactions, and other characteristics of the patients were recorded for 24 weeks. After study termination, a satisfaction survey was conducted. RESULTS: All enrolled patients and their liver grafts had survived for 24 weeks post-transplantation. No episodes of acute rejection were reported. Nine patients (18.8%) presented with adverse drug reactions that had been commonly reported with the use of other mycophenolate mofetil products, and no serious adverse drug reactions were reported. CONCLUSION: In conclusion, the My-rept 500-mg tablet appears to be feasible and convenient for administration to recipients of a liver transplant.

A clinical audit of high-cost and off-label drug use in dermatology.

BACKGROUND/OBJECTIVES: The use of high-cost, off-label, unsubsidised drugs has become valuable in the management of dermatology patients with challenging conditions unresponsive to conventional therapy. Currently, there is no dedicated funding and a paucity of evidence for such drugs. The aim of this audit was to review outcomes and costs. METHODS: A retrospective clinical audit of high-cost off-label dermatology drug applications to the High Cost Drug's Subcommittee was undertaken at a tertiary public hospital in Brisbane, Queensland, between 2002 and 2013. RESULTS: Of 28 applications, 25 were approved. The medications included thalidomide, mycophenolate mofetil, cyclosporin, infliximab, rituximab and adalimumab. Over 70% of patients responded to treatment. Individual annual costs for these medications ranged from $2068 to $36 984. Adverse effects resulted in drug withdrawal in five cases. CONCLUSIONS: Despite the absence of dedicated funding for high-cost drugs and a rigorous committee approval process, most applications were approved, of which >70% benefited from treatment. This audit provides useful clinical experience with off-label use of high-cost drugs in difficult dermatological conditions.

Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

BACKGROUND: End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES: To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS: Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association's electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time-state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. RESULTS: Eighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY. LIMITATIONS: For included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled. FUTURE WORK: High-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome. CONCLUSION: Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000-30,000 per QALY. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013189. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The Cost of Gastrointestinal Adverse Events and the Impact of Dose-Reductions/Discontinuations on Acute Rejection in Kidney Transplant Patients of Mycophenolate Mofetil-Related Compared to Enteric-Coated Mycophenolate Sodium: A Pharmacoeconomic Study.

BACKGROUND: Mycophenolate mofetil (MMF) is effective in decreasing rejection and graft loss in renal transplant patients. Enteric-coated mycophenolate sodium (EC-MPS) was designed to reduce MMF gastrointestinal (GI) effects. Dose manipulations in MMF/EC-MPS produce GI tolerability, increasing the risk of rejection. Significant differences in tolerance of MMF/EC-MPS may have economic influence in transplant efficacy outcomes. Herein, we performed a pharmacoeconomic evaluation of acute rejection incidence and interventions in GI-intolerant patients using MMF/EC-MPS. METHODS: A cost-effectiveness analysis was performed through a decision tree model with a 1-year time horizon estimating costs and effectiveness of MMF and EC-MPS in renal transplant patients with GI intolerance. The costs and use of resources (US dollars; USD) were from payer perspective (Mexican Social Security). Primary health outcomes were mean cost of acute rejection and GI adverse events treatment. A probabilistic sensitivity analysis (PSA) was generated to test robustness of the model. RESULTS: Calculated incidence of MMF GI intolerance was 44%, and calculated rejection incidence for MMF was 24.05%. Calculated incidence of EC-MPS GI intolerance was 29%, and calculated rejection incidence for EC-MPS was 20.1% Total cost of MMF with GI intolerance during 1-year period plus cost of treating one rejection sums $752,107.25 USD. Total cost of EC-MPS with GI intolerance plus cost of treating one rejection sums $638,018.97 USD. CONCLUSION: EC-MPS-based treatment is a cost-saving alternative vs MMF in GI-intolerant kidney transplant patients. PSA supports the decision to utilize EC-MPS based on cost-effectiveness analysis.

Preemptive Renal Transplantation-The Best Treatment Option for Terminal Chronic Renal Failure.

Renal transplantation is the best therapeutic option for end-stage chronic renal disease. Assuming that it is more advisable if performed early, we aimed to show the clinical, social, and economic advantages in 70% of our patients who were dialyzed only for a short period. For this purpose, we retrospectively collected data over 28 years in 142 kidney transplants performed in patients with <6 weeks on dialysis. 66% of our patients were 30-60 years old; 98% of the patients had living donors. At transplantation, 64% of our patients had no public support; however, 64% of them returned to work and got health insurance 2 months later. Full rehabilitation was achieved in all cases, including integration to the family, return to full-time work, school and university, sports, and reproduction. Immunosuppression consisted of 3 drugs, including steroids, cyclosporine, and azathioprine or mycophenolate. The cost in the 1st year, including patient and donor evaluation, surgery, immunosuppression, and follow-up, was $13,300 USD versus $22,320 for hemodialysis. We conclude that preemptive renal transplantation with <6 weeks on dialysis is the best therapeutic option for end-stage renal failure, especially in developing countries such as Bolivia, where until last year, full public support for renal replacement therapy was unavailable.

Multinational Evaluation of Mycophenolic Acid, Tacrolimus, Cyclosporin, Sirolimus, and Everolimus Utilization.

BACKGROUND: Increasing immunosuppressant utilization and expenditure is a worldwide challenge as more people successfully live with transplanted organs. Our aims were to characterize utilization of mycophenolate, tacrolimus, cyclosporin, sirolimus, and everolimus in Australian transplant recipients from 2007 to 2013; to identify specific patterns of usage; and to compare Australian utilization with Norwegian, Danish, Swedish, and the Netherlands use. MATERIAL AND METHODS: Australian utilization and expenditure data were captured through national Pharmaceutical Benefits Scheme and Highly Specialized Drug administrative databases. Norwegian, Danish, Swedish, and the Netherlands utilization were retrieved from their healthcare databases. Utilization was compared as defined daily dose per 1000 population per day (DDD/1000 population/day). Data on kidney transplant recipients, the predominant patient group prescribed these medicines, were obtained from international transplant registries. RESULTS: From 2007-2013 Australian utilization of mycophenolic acid, tacrolimus and everolimus increased 2.7-fold, 2.2-fold, and 2.3-fold, respectively. Use of cyclosporin and sirolimus decreased 20% and 30%, respectively. Australian utilization was significantly lower than European utilization (2013) but was increasing at a faster rate. Total Australian expenditure increased approximately AUD$30 million over the study period to almost AUD$100 million in 2013. Kidney transplantation rates increased across each country over this time, with Australia having the lowest rate. CONCLUSIONS: Immunosuppressant usage and subsequent expenditure are rising in Australia and Northern Europe. With increased numbers of people living with transplants, and the observed growth potential predicted from Northern European data, this class of medicines can be expected to continue consuming an increasing share of Australian pharmaceutical expenditure into the future.

Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis.

No previous study has compared mycophenolate mofetil (MMF) with low-dose cyclophosphamide (CYC) in the treatment of lupus nephritis (LN). To do so, we recruited patients with LN (class III, IV, or V) and randomized them to receive either low-dose CYC or oral MMF. Those with crescentic LN, a serum creatinine over 265 µmol/l, and neurological or pulmonary lupus were excluded. MMF was prescribed at daily doses of 1.5-3 g for 24 weeks, while CYC was administered as six fortnightly infusions of 500 mg each. All patients received three methylprednisolone injections, followed by oral corticosteroids. Maintenance therapy with azathioprine and low-dose corticosteroid was started at end of induction therapy. The primary end point was treatment response at 24 weeks, while secondary end points were complete remission, Systemic Lupus Erythematosus Disease Activity Index and adverse events. Of the 173 patients recruited, 100 were equally randomized to receive either CYC or MMF. Baseline characteristics were similar, except for higher 24 h proteinuria in the CYC group. At 24 weeks, 37 patients in each group achieved the primary end point. The complete remission rate was 50% in CYC and 54% in MMF group. Gastrointestinal symptoms were significantly more frequent in patients receiving MMF (52 vs. 4%). However, other adverse events were similar. Thus, low-dose intravenous CYC is comparable in safety and efficacy to oral MMF in the induction treatment of less severe LN.

Mycophenolic acid in dermatology a century after its discovery.

Mycophenolic acid was first discovered in 1913 and first used clinically in the 1970s as an immunosuppressant to prevent organ transplantation rejection. It was later used in the treatment of psoriasis. However due to its side-effect profile and fears over its carcinogenic potential it was abandoned. From the late 1990s a prodrug, mycophenolate mofetil (MMF), was developed and more recently, enteric-coated mycophenolate sodium (EC-MPS), both of which have gained increasing use in the field of dermatology for a variety of skin conditions. This review discusses the pharmacology, mechanisms of action, side-effects and current clinical applications in dermatology of MMF and EC-MPS.

Low-dose RATG with or without basiliximab in renal transplantation: a matched-cohort observational study.

BACKGROUND/AIMS: In renal transplantation, peri-operative low-dose rabbit-antithymocyte-globulin (RATG) plus basiliximab induction prevented acute allograft rejection more effectively than post-operative RATG plus basiliximab induction. We investigated the specific antirejection contribution of basiliximab in this context. METHODS: This single-center, observational, matched-cohort study evaluated allograft rejections (primary outcome), steroid exposure and side effects, GFR (iohexol plasma clearance) and treatment costs in 16 deceased-donor renal transplant recipients induced with RATG (0.5 mg/kg/day) and 32 age-, gender- and treatment-matched reference-patients given RATG plus basiliximab (20 mg on days 0 and 4). RESULTS: Induction was well tolerated. At 18 months, 8 patients (50%) vs. 3 reference-patients (9.4%) rejected the graft [HR (95% CI): 6.53 (1.73-24.70), p = 0.006]. Difference was significant (p < 0.01) even after adjusting for recipient/donor age and gender, cold ischemia time and HLA mismatches. There were 1 antibody-mediated rejection and 2 moderate cellular rejections in patients vs. none in reference-patients (p = 0.032). The median (interquartile range) prednisone cumulative dose was remarkably higher in patients than reference-patients [4.78 (1.12-6.10) vs. 0.19 (0.18-3.81) grams, p = 0.002]. Three patients vs. 24 reference-patients were off-steroid at study end (p < 0.001). Three patients vs. no reference-patient developed new-onset diabetes (p = 0.003). Both inductions similarly depleted B-cells. Outcomes of AZA- vs. MMF-treated participants were similar. GFR was similar in all groups. Compared to MMF, AZA therapy saved ≈ EUR 2,500/year and by month 14.3 post-transplant compensated basiliximab costs. CONCLUSION: In renal transplantation, basiliximab plus peri-operative low-dose RATG more efficiently prevented allograft rejection than RATG monotherapy, and minimized steroid exposure and toxicity. AZA- vs MMF-based maintenance immunosuppression largely compensated the extra costs of basiliximab.

Cost-effectiveness of modern mTOR inhibitor based immunosuppression compared to the standard of care after renal transplantation in Germany.

OBJECTIVES: Standards of immunosuppression in renal transplantation have changed dynamically in recent years. We here provide a refined advanced pharmacoeconomic model which uses state-of-the-art methods including a mixed treatment comparison (MTC) analysis. The aim was to assess the cost-effectiveness of current immunosuppressive therapy regimens (TR): "sirolimus + early withdrawal of cyclosporine + steroids" (TR1), "sirolimus-early transition" (TR2), "everolimus-early transition" (TR3) and "tacrolimus low dose + mycophenolate mofetil (MMF) + steroids" (TR4). METHODS: An up-to-date Markov model with current source data was employed to assess the cost-effectiveness of modern immunosuppressive regimens over 12-month and 10-year time periods. Transition probabilities for the occurrence of events for the first year were based on an MTC analysis. The robustness of the model was tested in extensive sensitivity analyses. RESULTS: Within the 12-month time period TR2 yields the highest life years (0.987 LY), generating costs of 17,500 . In terms of years with functioning graft (FG), TR4 yields the best efficacy over the 12-month model duration (0.970 years with FG). For the 10-year time period, TR2 yields the lowest costs (107,246 ) and dominates both TR3 and TR1, as it is simultaneously more effective. Within the 10-year model duration, TR4 reaches slightly higher effects compared with TR2 (6.493 vs. 6.474 LY) resulting in an incremental cost-effectiveness ratio of 387,684 per LY gained. CONCLUSIONS: The early transition to sirolimus provides long-term efficiency results comparable with a tacrolimus-based regimen, which represents a common treatment standard after kidney transplantation. Both are superior to other investigated immunosuppressive regimens.

Should mycophenolate mofetil replace cyclophosphamide as first-line therapy for severe lupus nephritis?

Available treatments for severe (class III, IV, and V) lupus nephritis (LN) have expanded greatly over the last 40 years. In the 1970s and 1980s, cyclophosphamide (CYC), in combination with glucocorticoids, gained favor as induction and maintenance therapy for severe LN. However, the adverse event profile of CYC led to the search for other medications for severe LN. Beginning in the late 1990 s, mycophenolate mofetil (MMF) was introduced as induction and maintenance therapy for severe LN. This review discusses the clinical trial results, pharmacology, cost-effectiveness, and adverse effect profiles of CYC compared to MMF for induction and maintenance therapy for severe LN. The authors conclude that MMF should be considered first-line induction and maintenance treatment therapy for severe LN, although CYC may have a place under specific clinical and economic circumstances.