ANSWERS MS addresses a common clinical question: “Is it safe and effective to switch to alemtuzumab if natalizumab fails in highly active MS?” Dr. Gallagher said. “The truth is we don’t really know the answer to this, although it’s becoming an increasingly used switch.”
Alemtuzumab was developed in Cambridge, England, in 1983, originally as an anticancer agent, and first started being used in MS patients in the 1990s. Natalizumab was first licensed in the United Kingdom in 2007.
The aim of the study was mainly to look at safety, but also examine efficacy, and to offer advice on how to best manage the switch. A total of 79 patients formed the safety cohort; 51 of these patients had more than 2 years of follow-up after their first infusion of alemtuzumab and formed the efficacy cohort.
Data were examined in five phases: before natalizumab, during natalizumab, during the switchover period, during alemtuzumab treatment, and after alemtuzumab treatment, with the latter starting 2 years after the first alemtuzumab infusion.
Dr. Gallagher noted that 43% started natalizumab as a first-line therapy, and almost half (49%) of patients stopped taking natalizumab because of breakthrough disease, making this a bit of an unusual cohort with highly active disease, although other cohort characteristics were pretty typical of an MS population.
“The headline is that there are no new safety concerns identified from this cohort,” Dr. Gallagher reported. “Most [61%] patients had infusion reactions with alemtuzumab as expected, but this gradually reduced with subsequent courses.”
Fewer than 20% of patients developed autoimmune thyroid disease, he added, and there were no cases of idiopathic thrombocytopenic purpura.
Infections were seen in nine patients, including three cases of shingles, two urinary tract infections – one of which was classed as a severe adverse event – and one case each of oral thrush, fungal skin infection, tonsillitis, and norovirus.
There was also one cytomegalovirus infection and one death from sepsis unrelated to alemtuzumab; both of these were classed as serious adverse events.
In terms of efficacy, mean ARRs were 2.3 before and 0.8 during natalizumab treatment, decreasing to 0.4 during alemtuzumab treatment and 0.5 post alemtuzumab. A “spike” in relapses was seen, however, during the switch period.
“There was a similar story with MRI imaging,” Dr. Gallagher said. “The profile suggests high disease activity during the switch phase in comparison to everything else.” The mean number of new or worsened MRI lesions was 4.32 per scan per year during the switch period. This fell, however, during alemtuzumab treatment to 0.006 per MRI scan per year and remained low after the end of alemtuzumab treatment at 0.017 per scan per year.
There was no real benefit to switching on the EDSS, with scores increasing from 3.4 in the pre-natalizumab period to 4.7 during the switch period, but then plateauing out to 4.4. and 4.3 after the initiation of alemtuzumab and in the post-alemtuzumab phase.
“These data were based on medical records, often incomplete, and so not all patients had an EDSS in every phase, for example,” Dr. Gallagher noted. He said an analysis was done to try to account for the missing information. This showed that there was an improvement in EDSS while on alemtuzumab, but the effect was not maintained.
It was evident in looking at the switch period that a shorter time between natalizumab and alemtuzumab was associated with the best outcomes, with the optimum time being around 2-4 months. Bridging therapy with fingolimod did not reduce disease activity during the switch, Dr. Gallagher said.
ANSWERS MS was funded by Sanofi-Genzyme. Paul Gallagher disclosed that he had received salary payment and travel funding for educational events from Sanofi-Genzyme and travel funding from Novartis and Biogen.
Dr. Frau disclosed that she serves on scientific advisory boards for Biogen, Merck, and Genzyme and that she has received honoraria for speaking from Merck Serono, Genzyme, Biogen, and Teva.
SOURCE: Frau J et al. Mult Scler. 2018;24(S2):100-1, Abstract 265; Gallagher P et al. Mult Scler. 2018;24(S2):99-100, Abstract 264.