Skip Navigation


Rheumatology Advance Access originally published online on April 4, 2007
Rheumatology 2007 46(7):1096-1101; doi:10.1093/rheumatology/kem054
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
46/7/1096    most recent
kem054v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Wilson, E. C. F.
Right arrow Articles by Fordham, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilson, E. C. F.
Right arrow Articles by Fordham, R. J.
Related Collections
Right arrow Health Economics
Right arrow Systemic Lupus Erythematosus and Autoimmunity
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The cost-effectiveness of mycophenolate mofetil as firstline therapy in active lupus nephritis

E. C. F. Wilson, D. R. W. Jayne1, E. Dellow2 and R. J. Fordham

Health Economics Group, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, 1Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ and 2Medical Affairs, Aspreva Pharmaceuticals Ltd, The Old Stables, Bagshot Park, Bagshot GU19 5PJ, UK.

Correspondence to: E. Wilson, Health Economics Group, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK. E-mail: ed.wilson{at}uea.ac.uk


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Objectives. Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect any system of the body. Involvement of the kidneys, lupus nephritis (LN), affects up to 50% of SLE patients during the course of their disease, and is characterized by periods of active disease (flares) and remission. For more severe nephritis, an induction course of immunosuppressive therapy is recommended. Options include intravenous cyclophosphamide (IVC) or mycophenolate mofetil (MMF), followed by a maintenance course, typically of azathioprine. The objective of this study is to determine which therapy results in better quality of life (QoL) for patients and which represents best value for money for finite health service resources.

Methods. A patient-level simulation model is developed to estimate the costs and quality-adjusted life-years (QALYs) of a patient treated with IVC or MMF for an induction period of six months. Efficacy, QoL, resource use and cost data are extracted from the literature and standard databases and supplemented with expert opinion where necessary.

Results. On average, the model predicts MMF to result in improved QoL compared with IVC. MMF is also less expensive than IVC, costing £1600 ({euro}2400; US$3100) less over the period, based on 2005 NHS prices. The major determinant and cost driver of this result is the requirement for a day-case procedure to administer IVC. Sensitivity analysis shows an 81% probability that MMF will be cost-effective compared with IVC at a willingness to pay of £30 000 ({euro}44 700; US$58 500) per QALY gained.

Conclusion. MMF is likely to result in better QoL and be less expensive than IVC as induction therapy for LN.

KEY WORDS: Lupus nephritis, Systemic lupus erythematosus, Lupus, Flare, Mycophenolate mofetil, Cyclophosphamide, Economic evaluation, Cost–utility analysis, Resource, Rationing


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect any system of the body. Lupus nephritis (LN) is the renal manifestation, characterized by periods of active disease (flares) and remission.

The annual incidence of SLE is approximately four per 100 000 adults, with a prevalence of 42 per 100 000 (based on US data) [1]. Of this, about 25–50% of patients will have renal involvement during the early course of their disease, with this figure rising to approximately 60% in the later stages [1].

The aims of LN treatment are to preserve renal function and protect the patient from long-term consequences, namely end-stage renal disease (ESRD) requiring dialysis or renal transplantation and death. Typically, renal flares are treated with high-dose oral or intravenous prednisolone plus either intravenous cyclophosphamide (IVC) or more recently oral mycophenolate mofetil (MMF), although at present neither of these is licensed for this indication. Upon remission of the flare, patients begin a maintenance regimen of lower dose prednisolone with azathioprine, cyclophosphamide or MMF. Ciclosporin and methotrexate are less commonly used alternatives with differing short- and long-term toxicities. The quality of the disease response to therapy is directly related to the risk of subsequent development of ESRD and/or death.

All healthcare systems are faced with finite resources. Therefore, managers and clinicians must make decisions as to the appropriate disposal of those resources to ensure best outcomes for patients. Knowledge of the cost-effectiveness of interventions can help in these rationing decisions.

The purpose of this study is to estimate the costs and consequences of two alternative induction therapy strategies for LN patients, namely prednisolone plus IVC and prednisolone plus MMF, from the perspective of the NHS. Once estimated, the costs and consequences of these alternatives can be compared and, as a result, the best value-for-money treatment can be identified.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
We developed a model simulating the costs and outcomes of treating a patient with either prednisolone plus MMF or prednisolone plus IVC over the period of induction therapy.

Literature review
A systematic review of the literature [2] identified two relevant studies comparing MMF and IVC, reporting results following induction therapy [3, 4]. Additional data were extracted from a Cochrane review of all treatments for LN [5].

Comparators
We compared the total cost and outcome [measured in quality-adjusted life-years (QALYs)] of induction therapy for an LN flare in a patient treated with either:

  1. prednisolone plus MMF (‘MMF strategy’) or
  2. prednisolone plus IVC (‘IVC strategy’).

As this was a study of the differences between the two strategies, treatments common to both arms have no impact on the results and were therefore excluded. Typically, these would include 3 x 750 mg intravenous bolus of methylprednisolone at commencement of therapy and 0.5–1.0 mg/kg of oral prednisolone daily [6]. Patients would also receive a proton pump inhibitor (for example, 20 mg of omeprazole daily) as prophylaxis against steroid-induced gastro-oesophageal erosion, fungal prophylaxis for the first six weeks of treatment and bisphosphonates and vitamin D where appropriate to counteract the effects of steroids on bone mineral density (BMD). Patients would also visit their nephrologist on an out-patient basis once a month. Drug and health service activity for each arm is summarized subsequently and in Table 1 [3, 4, 7, 8].


View this table:
[in this window]
[in a new window]

  		TABLE 1. Summary drug therapy and health service activity

 
MMF strategy
MMF is administered orally, at a mean dose of 2.7 g daily, with doses of between 1 and 3 g reported in trials [3, 7]. It is recommended that patients taking MMF undergo a complete blood count weekly for the first 4 weeks, every 2 weeks for the following 8 weeks and every 4 weeks for the next 52 weeks [8]. This equates to 11 blood tests in the first 6 months.

IVC strategy
There is some variation in dosing regimen for IVC therapy in the UK. For this model, the dosing schedule of IVC was based on Ginzler and Ong [3, 4]: IVC is administered as a monthly bolus of 1.275 g every 28 days (based on an average 0.75 g/m2 dose; range: 0.5–1 g/m2, or 0.85–1.7 g per patient per month). Patients usually receive an anti-emetic (typically a 5-HT3 antagonist, such as ondansetron) for 2 days following cyclophosphamide administration. A recommended regimen for ‘moderately emetogenic chemotherapy’ is 8 mg orally 1–2 h before treatment, then 8 mg every 12 h for up to 5 days [8].

Female patients receiving cyclophosphamide may receive ovarian protection treatment during their therapy. Goserelin is administered as a 3.6 mg implant every 28 days. We assumed that 20% of patients received this.

All patients received mesna to prevent haemorrhagic cystitis. There are a number of infusion regimens. For example, an intravenous bolus approach recommends 20% of cyclophosphamide dosed at 0, 4 and 8 h, or 40% at 0, 1, 4 and 7 h [9]. The total dose is thus between 60% and 160% of the cyclophosphamide dose (0.765–2.04 g).

IVC is administered in an out-patient setting, requiring a day-case appointment for observation and hydration of the patient, in addition to the regular monthly out-patient day-case visit. Patients also received a blood test every two weeks while undergoing therapy with IVC.

Modelling
The total cost and outcome per patient of each strategy were estimated by means of a patient-level simulation with 10 000 repetitions on each of the two strategies [10]. The transition period of the model is 12 weeks and costs and outcomes are summed over 24 weeks (~6 months) representing the induction period of therapy.

Within the model, a patient was defined in terms of five variables (Table 2). The treatment variable was MMF, IVC or ‘none’. Simulated patients in the MMF strategy started on MMF and those in the IVC strategy started on IVC. Patients switched or discontinued immunosuppressants (due to adverse events, AES) at rates determined from the literature (Table 3) [3]. It would be unrealistic for patients to receive no treatment whatsoever, therefore we assumed that such patients received a course of intravenous methylprednisolone administered as a monthly bolus of 1 g/m2 (average monthly dose of 1.75 g, range: 1.6–1.9 g) [11].


View this table:
[in this window]
[in a new window]

  		TABLE 2. Model variables

 

View this table:
[in this window]
[in a new window]

  		TABLE 3. Therapy switch rates per transition period (12 weeks) [3]

 
The disease status variable relates to the effectiveness of the treatment at inducing remission. A systematic review of treatments for induction in LN was recently undertaken to identify the effectiveness of MMF and IVC [2]. This review identified a number of relevant trials, of which two [3, 4] compared MMF and IVC as induction therapies for LN, reporting outcomes at six months and were thus relevant to this analysis. Response and AE rates for each were extracted from these studies (see Appendix 1 for details of meta-analysis). Response and AE rates for patients ceasing immunosuppressive therapy (that is, steroid monotherapy) were taken from a further meta-analysis of treatments for lupus (Table 4) [3–5].


View this table:
[in this window]
[in a new window]

  		TABLE 4. Response to treatment per transition period (12 weeks) [3–5]

 
A major infection is one requiring hospitalization of the patient, and a minor, an infection such as zoster, requiring primary care treatment only. The risks of developing one or other are dependent on the treatment (MMF, IVC or none) and are extracted from the literature (Table 5) [3, 4]. For patients having ceased immunosuppressive therapy, a recent Cochrane review [5] found no significant difference in infection rates between patients treated with steroids alone and steroids plus IVC. However, there are data suggesting the incidence of serious infection in patients treated for vasculitis doubles when IVC is combined with steroids [12, 13] and in the experience of one of the authors (D.J.) and indirect evidence [14, 15] it was considered unlikely that the infection rate for steroids alone would be higher than for steroids plus MMF. Following the Cochrane review evidence, we therefore assumed that the infection rates for steroid treatment were equal to those for IVC (Table 5) [3, 4], but varied this assumption in a scenario analysis, setting the infection rates for steroid treatment equal to those for MMF. Details of the meta-analysis are in Appendix 1.


View this table:
[in this window]
[in a new window]

  		TABLE 5. Incidence of adverse events per transition period (12 weeks)

 
The simulation was repeated 10 000 times for both the IVC strategy as well as for the MMF strategy, generating a mean cost and QALY score for each treatment option. An incremental analysis demonstrated the relative cost-effectiveness of the two options.

Costs
Costs considered in the model were drug acquisition and administration, concomitant medications and treatment of major and minor infections. The price-year was 2005, and the cost-perspective that of the NHS; as this was a comparison of the differences between treatments, cost items identical to both arms were excluded (Table 6) [8, 11, 16, 17]. Unit costs are summarized in Appendix 1. As the time horizon of this model is <1 yr, discounting future costs was not relevant.


View this table:
[in this window]
[in a new window]

  		TABLE 6. Summary of mean cost inputs

 
Outcomes
The outcome of the model is the QALY. Quality of life (QoL) is measured as utility, with a value of 1 assigned to full health, and 0 to death. States less than full health but better than death are assigned proportionately between 0 and 1 (and states considered worse than death score below 0). The disutility of a health state is the impact of that disease state on QoL (= 1 – utility). QALYs are calculated as the utility of a health state multiplied by the time spent in that health state. Estimates of the disutility of health states were based on preference scores extracted from the Harvard Cost-Effectiveness Analysis Registry [18]. The utility of a particular individual is calculated as 1 – disutility for health state – disutility for events. For example, a patient with active disease has a utility of 1 – 0.61 = 0.39.

Table 7 is divided into chronic and acute states [18–22]. For chronic states, the patient was assumed to remain at the same health status for the full 12-week transition. Thus, 12 weeks spent in active disease is (1 – 0.61) x 12/52 = 0.09 QALYs. A minor infection was assumed to last for 5 days, and a major infection for 14 days. Therefore, the QALY figure for a patient in active disease with a minor infection was 0.09 – (0.28 x 5/365) = 0.086.


View this table:
[in this window]
[in a new window]

  		TABLE 7. Utility scores [19]

 
Sensitivity analysis
Uncertainty within the analysis is presented as a cost-effectiveness acceptability curve, which shows the probability that MMF is the cost-effective strategy for a range of values of willingness to pay for a QALY. The curve is generated by calculating the proportion of the 10 000 iterations where the incremental cost-effectiveness ratio (ICER) is below a given threshold [23].


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusion
 Acknowledgements
 References
 
Mean outcomes
MMF is the least costly strategy, costing £1388 over the 24-week period, compared with £2994 for IVC (note this excludes the cost of treatments common to both arms). The incremental cost is thus £1606 ({euro}2395; US$3135). MMF also results in superior QoL, with 0.26 QALYs compared with 0.22 for IVC. Therefore, on average, MMF ‘dominates’ IVC: it is both more effective and less expensive (Table 8).


View this table:
[in this window]
[in a new window]

  		TABLE 8. Mean results

 
Sensitivity analysis
The 10 000 pairs of incremental costs and QALYs generated from the model are plotted in Fig. 1. The majority of points are below the x-axis, suggesting that MMF is less expensive than IVC most of the time. More than half of points are to the right of the y-axis, suggesting that MMF is more effective for the majority of patients. There is a clustering of points along the y-axis, representing instances when there is no difference in outcome between the two treatments.


Figure 1
View larger version (19K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		FIG. 1. Scatter plot of cost–QALY increments.

 
A cost-effectiveness acceptability curve was generated by calculating the proportion of points where the ICER is below a given threshold (willingness to pay for a QALY; Fig. 2). The proportion of the points for which one treatment is optimal at a given threshold is interpreted as the probability that that particular treatment is the cost-effective option for that threshold.


Figure 2
View larger version (5K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		FIG. 2. Cost-effectiveness acceptability curve.

 
At a willingness to pay of £0 (representing an extreme definition of cost-effectiveness where a decision-maker is concerned solely about cost and not willing to pay anything for any gain in QoL), the probability that MMF is ‘optimal’ is 95%; that is, there is a 95% probability that treatment with MMF will be less expensive than IVC. At the opposite extreme, with an infinite willingness to pay for a QALY (where a decision-maker has no regard for cost and is solely interested in QoL), the probability that MMF is cost-effective tends towards approximately 70%; that is, there is a 70% probability that MMF is more effective than IVC.

Taking into account both cost and QALYs, the typical willingness to pay for a QALY in the UK NHS is between £25 000 and £35 000 ({euro}37 300 – 52 200; US$48 800 – 68 300). Our results suggest a probability of approximately 81% that MMF will be cost-effective compared with IVC.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusion
 Acknowledgements
 References
 
On average, MMF is the less expensive of the two strategies and also appears to result in a higher QoL compared with IVC. Therefore, MMF ‘dominates’ IVC. Investigation of uncertainty around this point estimate shows that there is an 81% probability that MMF will cost <£30 000 ({euro}44 700; US$58 500) for each incremental QALY. The reason for the cost difference (and the major cost driver) is the requirement for a day-case procedure to administer IVC and the reasons for the QoL difference are a higher response rate and a lower risk of infections.

To our knowledge, this is the first cost–utility analysis comparing MMF with IVC for induction therapy in LN patients. Previous studies collecting and analysing cost and/or QoL data for SLE patients have been published [24–27], but these are not specific to LN. McInnes et al. [28] compared prednisolone monotherapy with IVC and estimated the potential savings to society from using IVC over a period of 10 yrs to be $93.1 million. The major cost drivers were prevention of ESRD and increased labour productivity owing to patients remaining economically active. The perspective of our analysis was restricted to health service costs and so excluded the potential benefits from increased economic activity. Our results suggest that, on average, MMF will be less expensive than IVC over 6 months and the higher remission rate observed with MMF implies that the wider benefits to the economy may be even greater.

The data required to support this model were extracted from two systematic reviews supplemented with other literature as necessary, but when data were not available, reliance on expert opinion and assumptions was required. Nevertheless, one-way sensitivity analyses (Appendix 2) demonstrated that the results were robust to all parameters within ‘reasonable’ ranges, except when the 12-week response rate to IVC was implausibly high (>72.5%).

Discussion with an expert panel revealed differences of opinion as to the probability of patients switching therapies (in particular, the proportion switching to ‘no immunosuppressive’) and the risk of infection from patients not treated with immunosuppressives. Rerunning the model under alternative switch and infection rate scenarios resulted in very little change to the mean results: IVC was still dominated by MMF (Appendix 3). Major infections may lead to dose reduction, with potential loss of efficacy. A limitation of the model is that this effect is not captured; but as MMF has a lower frequency of major infection, excluding this effect will bias the model against MMF.

It should be noted that this model considers only the first 6 months of a patient's therapy (induction treatment). It is therefore not possible to comment on the cost-effectiveness of longer-term maintenance therapy at this stage. Anecdotal evidence suggests patients initiated on MMF are not routinely switched to azathioprine following remission and this will have implications on outcomes and cost. Long-term experience with MMF is still quite limited [7, 29] and further work is ongoing to determine the longer-term clinical outcomes of using MMF as a maintenance therapy [30].

Additionally, the model does not consider the critical outcomes of renal failure and death. The primary motivation in commencing immunosuppressive therapy in patients with LN is preservation of renal function, and these benefits are unlikely to be observed within a period of six months. However, there is some evidence to suggest that early remission in the induction phase correlates with reduced risk of progression to ESRD [6] and, as more data become available, the long-term cost-effectiveness of alternative maintenance therapies can be assessed.

The major drivers of the result of our analysis are differences in remission and infection rates, as well as the need for a dedicated out-patient appointment to administer IVC. A limitation in developing this model was the lack of a strictly defined dosing regimen for IVC in common practice. For the purpose of this model, we defined an explicit regimen. Thus, the applicability of these results to alternative settings depends on the degree to which practice varies from that stated here.

Neither MMF nor IVC are licensed for induction therapy in LN, although a large randomized, controlled trial [30] is currently underway to establish the role of MMF as induction therapy in comparison with IVC, followed by a maintenance study in comparison with azathioprine. While these results are awaited, our study indicates a positive economic benefit from the use of MMF as induction therapy in LN patients.


   Conclusion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
Acknowledgements
 References
 
Induction therapy with MMF for patients with LN is likely to result in better QoL and be less expensive than IVC. The major factors determining this result are the requirement for a day-case procedure to administer IVC and ensure adequate hydration of the patient as well as the increased incidence of AES, particularly major infection, in patients receiving IVC.

The evidence base informing us about the longer-term consequences and costs of MMF as a maintenance therapy is currently limited. Further research is under way to evaluate this compared with alternative strategies in maintenance of disease remission for LN patients.

Formula


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
References
 
This health economics study was funded by Aspreva Pharmaceuticals Ltd.

The authors wish to thank Dan Jackson, Health Economist, Aspreva Pharmaceuticals, for his comments on drafts, and the clinical expert advisory panel: David D’Cruz, Honorary Senior Lecturer and Consultant Rheumatologist, The Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London; Liz Lightstone, Senior Lecturer in Nephrology and Honorary Consultant Physician, Imperial College London and The West London Renal and Transplant Centre, Hammersmith Hospital, London; Ken Smith, Genzyme Professor of Experimental Medicine, University of Cambridge and Consultant in Nephrology, Addenbrooke's Hospital, Cambridge.

EW and RF received consultancy fees from Aspreva Pharmaceuticals Ltd to develop this model via Hayward Medical Communications Ltd, Newmarket, Suffolk. DJ has received fees from Aspreva and ED is an employee of Aspreva.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 

  1. Cameron JS. Lupus nephritis. J Am Soc Nephrol (1999) 10:413–24.[Free Full Text]
  2. Moore RA, Derry S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther (2006) 8:R182.[CrossRef][Medline]
  3. Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med (2005) 353:2219–28.[Abstract/Free Full Text]
  4. Ong LM, Hooi LS, Lim TO, et al. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (2005) 10:504–10.[CrossRef][Medline]
  5. Flanc RS, Roberts MA, Strippoli GFM, Chadban SJ, Kerr PG, Atkins RC. Treatment for lupus nephritis. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD002922. DOI: 10.1002/14651858.CD002922.pub2.
  6. Houssiau FA, Vasconcelos C, D'Cruz D, et al. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial. Arthritis Rheum (2004) 50:3934–40.[CrossRef][ISI][Medline]
  7. Chan TM. Lupus nephritis: induction therapy. Lupus (2005) 14(Suppl. 1):S27–32.[CrossRef][ISI][Medline]
  8. Mehta DK, Martin J, Costello I, et al, eds. British National Formulary 49. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.
  9. British Colombia Cancer Agency. 15 January 2007. Mesna. www.bccancer.bc.ca/HPI/drugdatabase/drugindexpro/mesna.htm.
  10. Briggs A, Claxton K, Sculpher M. Further Developments in decision analytic models for economic evaluation. In: Decision modelling for health economic evaluation—Gray A, Briggs A, eds. (2006) Oxford: Oxford University Press. 58–65.
  11. Gourley MF, Austin HA 3rd, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med (1996) 125:549–57.[Abstract/Free Full Text]
  12. Guillevin L, Jarrousse B, Lok C, et al. Longterm followup after treatment of polyarteritis nodosa and Churg-Strauss angiitis with comparison of steroids, plasma exchange and cyclophosphamide to steroids and plasma exchange. A prospective randomised trial of 71 patients. The Cooperative Study Group for Polyarteritis Nodosa. J Rheumatol (1991) 18:567–74.[ISI][Medline]
  13. Illei GG, Austin HA, Crane M, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med (2001) 135:248–57.[Abstract/Free Full Text]
  14. Wiesel M, Carl S. A placebo controlled study of mycophenolate mofetil used in combination with cyclosporine and corticosteroids for the prevention of acute rejection in renal allograft recipients: 1-year results. The European Mycophenolate Mofetil Cooperative Study Group. J Urol (1998) 159:28–33.[CrossRef][ISI][Medline]
  15. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet (1995) 345:1321–5.[ISI][Medline]
  16. Curtis L, Netten A. Unit Costs of Health and Social Care 2005. (2005) University of Kent at Canterbury: Kent: Personal Social Services Research Unit.
  17. Department of Health. NHS reference costs 2005. 15 January 2007. www.dh.gov.uk/PublicationsAndStatistics/Publications/PublicationsPolicyAndGuidance/ PublicationsPolicyAndGuidanceArticle/fs/en?CONTENT_ID=4133221&chk=TxHkqo.
  18. Tufts New England Medical Center. The Cost Effectiveness Analysis Registry. In: Preference Weights 1998–2001. 15 January 2007. www.tufts-nemc.org/cearegistry/data/docs/phaseIIpreferenceweights.pdf.
  19. Smith KJ, Roberts MS. Cost effectiveness of vaccination strategies in adults without a history of chickenpox. Am J Med (2000) 108:723–9.[CrossRef][ISI][Medline]
  20. Smith KJ, Roberts MS. Antiviral therapies for herpes zoster infections. Are they economically justifiable? Pharmacoeconomics (2000) 18:95–104.[ISI][Medline]
  21. Balk EM, Zucker DR, Engels EA, Wong JB, Williams JW Jr, Lau J. Strategies for diagnosing and treating suspected acute bacterial sinusitis: a cost-effectiveness analysis. J Gen Intern Med (2001) 16:701–11.[CrossRef][ISI][Medline]
  22. Smith KJ, Roberts MS. Cost effectiveness of newer antiviral agents for herpes zoster: is the evidence spotty? J Infect Dis (1998) 178(Suppl. 1):S85–90.[ISI][Medline]
  23. Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL. Economic evaluation using patient-level data. In: Methods for the economic evaluation of health care programmes—Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL, eds. (2005) 3rd. Oxford: Oxford University Press. 258–67.
  24. Clarke A. Economic impact of lupus. Am J Manag Care (2001) 7(Suppl):S496–S501.[ISI][Medline]
  25. Clarke AE, Bloch DA, Danoff DS, Esdaile JM. Decreasing costs and improving outcomes in systemic lupus erythematosus: using regression trees to develop health policy. J Rheumatol (1994) 21:2246–53.[ISI][Medline]
  26. Clarke AE, Penrod J, St Pierre Y, et al. Underestimating the value of women: assessing the indirect costs of women with systemic lupus erythematosus. Tri-Nation Study Group. J Rheumatol (2000) 27:2597–604.[ISI][Medline]
  27. Sutcliffe N, Clarke AE, Taylor R, Frost C, Isenberg DA. Total costs and predictors of costs in patients with systemic lupus erythematosus. Rheumatology (2001) 40:37–47.[Abstract/Free Full Text]
  28. McInnes PM, Schuttinga J, Sanslone WR, Stark SP, Klippel JH. The economic impact of treatment of severe lupus nephritis with prednisone and intravenous cyclophosphamide. Arthritis Rheum (1994) 37:1000–6.[ISI][Medline]
  29. Cross J, Dwomoa A, Andrews P, et al. Mycophenolate mofetil for remission induction in severe lupus nephritis. Nephrol J Clin Pract (2005) 100:c92–100.[CrossRef]
  30. Aspreva Pharmaceuticals Ltd. A prospective, randomized, active controlled, parallel group, multi-center trial to assess the efficacy and safety of mycophenolate mofetil (MMF) in inducing response and maintaining remission in subjects with lupus nephritis. 15 January 2007. www.clinicaltrials.gov/ct/show/NCT00121082.
Submitted 6 November 2006; Accepted 8 February 2007


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 LupusHome page
T. Chan
Mycophenolate mofetil in the treatment of lupus nephritis - 7 years on
Lupus, July 1, 2008; 17(7): 617 - 621.
[PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
46/7/1096    most recent
kem054v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Wilson, E. C. F.
Right arrow Articles by Fordham, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilson, E. C. F.
Right arrow Articles by Fordham, R. J.
Related Collections
Right arrow Health Economics
Right arrow Systemic Lupus Erythematosus and Autoimmunity
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?