Authors' objectives: HTW undertook an evidence review to address the following question: is autologous haematopoietic stem cell transplantation (AHSCT) clinically and cost-effective for previously treated, relapsing-remitting multiple sclerosis (RRMS)?

Authors' results and conclusions: This Evidence Appraisal Report was adapted from the advice statement produced by the Scottish Health Technologies Group (SHTG), “Autologous haematopoietic stem cell transplant for patients with highly active relapsing remitting multiple sclerosis not responding to high-efficacy disease modifying therapies”, published in 2019. One randomised control trial (RCT), the Multiple Sclerosis International Stem Cell Transplant Trial (MIST), was included in the SHTG advice statement and no further RCTs comparing AHSCT with current practice for people with MS (specifically RRMS or related terms) were identified for this report. Four systematic reviews were identified, of which one had been included in the SHTG advice statement. Ten additional primary studies were identified that had not been included in the systematic reviews. The evidence in the primary studies is limited by the variability in treatment protocols (conditioning regimens), patient inclusion criteria, outcome definitions, lack of comparator treatment and short follow up periods. The evidence extracted from the RCT, the relevant studies in the systematic reviews and the ten additional primary studies related to numerous relevant clinical outcomes (over twenty). Two measures reported most widely (including by the RCT) are 'no evidence of disease activity' (NEDA) and expanded disability status scale (EDSS). NEDA-3 was attained by 76% and 70% of patients at 24 months and five years post-AHSCT respectively (two studies, RRMS population) with NEDA-4 reached by 50% at five years post-AHSCT. A third study described NEDA-3 attainment by 90%, 70% and 60% of RRMS patients at one-, two- and three-years post-AHSCT respectively. A non-randomised study reported NEDA-3 to be higher for AHSCT compared with alemtuzumab for RRMS patients while the MIST RCT also found NEDA-3 to be significantly higher for AHSCT compared with disease modifying therapies (DMTs). EDSS decreased from baseline with AHSCT in all studies, with the exception of one, that reported this endpoint (seventeen studies). EDSS also decreased where reported for RRMS specifically (six studies). The MIST RCT found the difference in EDSS between AHSCT and DMTs at one-year post-AHSCT to be statistically significantly in favour of AHSCT. No studies evaluating the cost-effectiveness of AHSCT for previously treated relapsing remitting multiple sclerosis were identified. HTW developed a cost-utility analysis to determine the cost effectiveness of AHSCT compared with DMTs for people with highly active RRMS. A Markov model was used to estimate costs and quality-adjusted life years (QALYs) over a five year time horizon, from the UK NHS and personal social services perspective. Costs and QALYs were discounted at 3.5% per year as recommended in the NICE reference case. AHSCT was found to be dominant (more effective and less costly than DMTs) in most modelled scenarios with some notable exceptions. In these scenarios, AHSCT was still found to be more effective but it was also found to be more costly. When compared against all DMTs, the incremental cost effectiveness ratio (ICER) was found to be £38,359 per QALY gained indicating that AHSCT was not cost-effective as the ICER was above the threshold of £20,000 per QALY gained. When compared against natalizumab only, the ICER was found to be £2,741 per QALY gained indicating that AHSCT was cost-effective as the ICER was below the threshold of £20,000 per QALY gained. Probabilistic sensitivity analysis (PSA) was conducted to assess the combined parameter uncertainty in the model. In this analysis, the mean values that were utilised in the base case are replaced with values drawn from distributions around the mean values. The model is run 10,000 times. At a threshold of £20,000 per QALY, AHSCT was found to have a 100% probability of being cost-effective while standard care with DMTs had a 0% probability of being cost-effective. The appropriate mechanism for patient engagement was determined and the patient perspective was considered where possible.

Authors' recommendations: The evidence supports the routine adoption of autologous haematopoietic stem cell transplantation (AHSCT) for people with relapsing-remitting multiple sclerosis (RRMS), in patients who have recurrence of symptoms despite previous treatment with disease modifying therapies (DMTs). The use of AHSCT increases progression-free survival, slows the onset of disability and improves quality of life compared with DMTs. Patient selection for AHSCT should be undertaken by specialist MS-AHSCT Multi-Disciplinary Teams (MDTs) with neurological and haematological representation. The AHSCT treatment should be delivered in professionally accredited centres with neuro-rehabilitation and support services available to maximise the patient benefits of the treatment. Patient consent should include the provision of sufficient information to support shared decision-making and ensure that patients understand the safety, efficacy and uncertainties associated with AHSCT as well as alternative therapies. A cost-utility analysis found that treatment with AHSCT is more effective and less costly than DMTs in people with highly active RRMS. Further research into the effectiveness of AHSCT using RCTs and appropriate high efficacy DMTs over longer timeframes is recommended.

Authors' methods: The Evidence Appraisal Report is based on a literature search (strategy available on request) for published clinical and economic evidence on the health technology of interest. It is not a full systematic review but aims to identify the best available evidence on the health technology of interest. Researchers critically evaluate and synthesise this evidence. We include the following clinical evidence in order of priority: systematic reviews; randomised trials; non-randomised trials. We only include evidence for “lower priority” evidence where outcomes are not reported by a “higher priority” source. We also search for economic evaluations or original research that can form the basis of an assessment of costs/cost comparison. We carry out various levels of economic evaluation, according to the evidence that is available to inform this.

Authors' identified further research: Further research into the effectiveness of AHSCT using RCTs and appropriate high efficacy DMTs over longer timeframes is recommended

Project Status: Completed

Year Published: 2020

URL for published report: https://www.healthtechnology.wales/reports-guidance/autologous-haematopoietic-stem-cell-transplantation/

English language abstract: An English language summary is available

Publication Type: Rapid Review

Country: Wales, United Kingdom

Organisation Name: Health Technology Wales

Contact Address: Floor 3, 2 Capital Quarter, Tyndall Street, Cardiff, CF10 4BZ

Contact Name: Susan Myles, PhD

Contact Email: healthtechnology@wales.nhs.uk

Copyright: Health Technology Wales