Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study

Abstract

The newer immunosuppressant drugs (basiliximab, daclizumab, tacrolimus and MMF) consistently reduced the incidence of short-term (1-year) acute rejection compared with conventional immunosuppressive therapy. The independent use of basiliximab, daclizumab, tacrolimus and MMF was associated with a similar absolute reduction in 1-year acute rejection rate (approximately 15%). However, the effects of these drugs did not appear to be additive (e.g. benefit of tacrolimus with adjuvant MMF was 5% reduction in acute rejection rate compared with 15% reduction with adjuvant AZA). Thus, the addition of one of these drugs to a baseline immunosuppressant regimen was likely to affect adversely the incremental cost-effectiveness of the addition of another. The trials did not assess how the improvement in short-term outcomes (e.g. acute rejection rate or measures of graft function), together with the side-effect profile associated with each drug, translated into changes in patient-related quality of life. Moreover, given the relatively short duration of trials, the impact of the newer immunosuppressants on long-term graft loss and patient survival remains uncertain. The absence of both long-term outcome and quality of life from trial data makes assessment of the clinical and cost-effectiveness on the newer immunosuppressants contingent on modelling based on extrapolations from short-term trial outcomes. The choice of the most appropriate short-term outcome (e.g. acute rejection rate or measures of graft function) for such modelling remains a matter of clinical and scientific debate. The decision to use acute rejection in the meta-model in this report was based on the findings of a systematic review of the literature of predictors of long-term graft outcome. Only a very small proportion of the RCTs identified in this review assessed patient-focused outcomes such as quality of life. Since immunosuppressive drugs have both clinical benefits and specific side-effects, the balance of these harms and benefits could best be quantified through future trials using quality of life measures. The design of future trials should be considered with a view to the impact of drugs on particular renal transplant groups, particularly higher risk individuals and children. Finally, there is a need for improved reporting of methodological details of future trials, such as the method of randomisation and allocation concealment. A number of issues exist around registry data, for example the use of multiple drug regimens and the need to assess the long-term outcomes. An option is the use of observational registry data including, if possible, prospective data on all consecutive UK renal transplant patients. Data capture for each patient should include immunosuppressant regimens, clinical and patient-related outcomes and patient demographics.

Ciclosporina versus tacrolimus no transplante renal no Brasil: uma comparação de custos

“…O principal objetivo dessa terapia é aumentar a sobrevida do enxerto, evitando as rejeições agudas e crônicas do órgão transplantado 3,4,5 .…”

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

“…This will be done by conducting a systematic review of clinical effectiveness studies and a model-based economic evaluation of induction and maintenance immunosuppressive regimens to update the current guidance (TA85). 43 The current guidance was primarily based on research evidence presented to NICE in the assessment report by Woodroffe et al 65 We have incorporated relevant evidence that was presented in this previous report and we report new evidence from 2002 to the present. This will include a new decision-analytic model of kidney transplantation outcomes to investigate which regimen is the most cost-effective option.…”

“…In addition, studies included in the reviews conducted by Woodroffe et al 65 and Yao et al 67 were screened for inclusion against the eligibility criteria for this review.…”

Investigating the health-economic profiles of biomarker-driven immunosuppresion (BIO-DrIM) following solid organ transplantation

“…Many health-economic evaluations have been conducted in the field of IS medication [4,[12][13][14] , but to our knowledge there is no health-economic evaluation published to-date about the cost-effectiveness and/or cost-utility of a biomarker-guided (individualized) reduced IS medication plan following solid organ transplantation.…”

“…This is particularly striking not only in light of the many undesirable side-effects that limit the overall effectiveness and the patient's adherence to therapy, but importantly also in light of the high cost of IS-induction therapy with Basiliximab or Alemtuzumab. For example, the 2-year costs of four different immunosuppressive strategies, either based on Sirolimus, Cyclosporine, Everolimus or Tacrolimus, have been shown to vary between 26,732 EUR and 49,978 EUR [4] . Organ-tolerance in patients that are effectively on low IS medication or no IS medication at all, has been observed in many patients with various transplanted types of allografts [5][6][7] .…”