Evidence does not support the use of autologous haematopoietic stem cell transplantation (AHSCT) in preventing worsening disability in patients with progressive multiple sclerosis and low relapse activity, an Australian-led study has found.
The observational study indicated AHSCT was not superior to natalizumab in preventing disability worsening, with natalizumab the chosen comparator due to previous results showing a lack of effect on disability in progressive MS.
Researchers used a composite cohort from seven specialised centres and the MSBase international registry, which included 39 patients with MS treated with AHSCT (mean age 37, Expanded Disability Status Scale 5.7, 28% with recent disability progression, annualised relapse rate 0.54 during the preceding year).
They were propensity score matched with 65 patients treated with natalizumab.
Findings showed no difference between AHSCT and natalizumab when used in progressive MS, with a similar cumulative hazard of 6-month confirmed disability worsening between the groups (HR 1.49 to 3.14) over up to four years.
Similarly, there was no evidence of a difference in the cumulative probability of a 6-month confirmed disability improvement (HR 1.50 to 10.28).
The relapse activity was also similar (mean 0.08; HR 1.05 to 2.82) between the groups, said the authors, led by Australian neurologist Professor Tomas Kalincik from the University of Melbourne.
In the AHSCT group, three patients experienced febrile neutropenia during mobilisation, nine experienced serum sickness, six required intensive care unit admission and 36 patients experienced complications after discharge.
No treatment-related deaths were reported.
“It would be conceivable that patients with active progressive MS, who also had experienced a relapse during the preceding two years, would potentially benefit more from AHSCT in comparison with natalizumab – similar to the observation in relapsing- remitting MS,” the study authors wrote in the Journal of Neurology, Neurosurgery, and Psychiatry [link here].
“However, even though half of our present study cohort had experienced a relapse during the preceding two years, the study did not find any difference in the effectiveness of the two therapies either on the disability or, notably, on relapse outcomes.”
The authors noted a need for more research, particularly RCTs, as there was limited information to guide the use of AHSCT among patients with progressive MS.
“Given the considerable difficulties in conducting an appropriately blinded randomised controlled trial of AHSCT among patients with prominently progressive MS forms, rigorously conducted analysis of the available observational data represents the most suitable solution to generating this essential information,” they said.
They concluded that the results of their study did not support standard use of AHSCT in progressive MS with low level of episodic focal inflammatory activity.
“Even though the study was not powered to identify small-to-moderate magnitudes of treatment effect, such effects of AHSCT on disability would not be of sufficient clinical importance to justify its use in progressive MS, given its intensity and the risk of treatment-related adverse events,” they added.
Some authors declared financial ties to pharmaceutical companies.