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BERLIN – Switching to alemtuzumab from fingolimod is associated with improved disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to the results of a real-world study reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Jessica Frau, MD, of the University of Cagliari (Italy) reported that a switch from fingolimod (Gilenya) to alemtuzumab (Lemtrada) in 77 patients treated at 11 Italian centers was able to “reduce dramatically disease activity in patients who did not respond to fingolimod.”
Dr. Frau reported: “When we compared in our cohort the last year of fingolimod with the first year after the first course of alemtuzumab, we found a significant decrease in the annualized relapse rate [ARR].” The ARRs were 0.60 for fingolimod and 0.20 after 1 year of alemtuzumab treatment.
“We found also a trend towards an improvement in the EDSS [Expanded Disability Status Scale] score (P = .23), and less evidence of disease activity on MRI, both in terms of new T2 lesions and gadolinium-enhancing (Gd+) lesions.”
The last MRI during fingolimod treatment showed new T2 and Gd+ enhancing lesions in 69.2% and 58.6% of patients, respectively. Corresponding figures for the first MRI during alemtuzumab treatment were 10.4% and 2.2% of patients.
The beneficial effects of switching to fingolimod in the Italian study “was not influenced by a shorter washout [period] or a low lymphocyte count when alemtuzumab was started,” Dr. Frau said. A shorter washout period has been hypothesized to account for recent accounts of disease flares seen when switching from fingolimod to alemtuzumab, she explained.
Indeed, Dr. Frau noted that there had been a few studies that reported MS disease reactivation soon after the switch to alemtuzumab was made, which could be because lymphocytes remain in the lymph nodes when alemtuzumab is administered, this means that potentially they could repopulate the central nervous system and reactivate the disease.
However, “when alemtuzumab is started after fingolimod it is not a risk factor for reactivation of the disease,” Dr. Frau said, based on the current study’s findings.
As expected, the frequency of relapses increased during the washout period after stopping fingolimod, going from 12.7% of patients with relapse in the first month, 18.2% at 2 months, and 22.2% at 3 months. The time to first relapse from the start of alemtuzumab treatment was 6 months for 2.9% of patients, 9 months for 10.5% of patients, and 1 year for 20.7% of patients.
Asked to comment on when the optimal time to switch from fingolimod to alemtuzumab might be, Dr. Frau said: “The optimal time could be 1 month when the lymphocyte count is not too low.” However, lymphocyte counts were not measured in the entire cohort, so “these data perhaps need to have more strength.”
The switch from natalizumab to alemtuzumab
Other data on switching to alemtuzumab, this time from natalizumab (Tysabri), in the ANSWERS MS study were presented by Paul Gallagher, MBChB, of Queen Elizabeth University Hospital, London, and the University of Glasgow (Scotland).
ANSWERS MS (Alemtuzumab after Natalizumab Switch in Evolving Rapidly Severe MS) is a retrospective, observational analysis of routinely collected data on the use of alemtuzumab by 13 centers the United Kingdom and Ireland. These centers have been collecting data since before alemtuzumab was licensed in 2014 for MS, Dr. Gallagher observed, with some centers having experience of making the switch for more than a decade.
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.
BERLIN – Switching to alemtuzumab from fingolimod is associated with improved disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to the results of a real-world study reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Jessica Frau, MD, of the University of Cagliari (Italy) reported that a switch from fingolimod (Gilenya) to alemtuzumab (Lemtrada) in 77 patients treated at 11 Italian centers was able to “reduce dramatically disease activity in patients who did not respond to fingolimod.”
Dr. Frau reported: “When we compared in our cohort the last year of fingolimod with the first year after the first course of alemtuzumab, we found a significant decrease in the annualized relapse rate [ARR].” The ARRs were 0.60 for fingolimod and 0.20 after 1 year of alemtuzumab treatment.
“We found also a trend towards an improvement in the EDSS [Expanded Disability Status Scale] score (P = .23), and less evidence of disease activity on MRI, both in terms of new T2 lesions and gadolinium-enhancing (Gd+) lesions.”
The last MRI during fingolimod treatment showed new T2 and Gd+ enhancing lesions in 69.2% and 58.6% of patients, respectively. Corresponding figures for the first MRI during alemtuzumab treatment were 10.4% and 2.2% of patients.
The beneficial effects of switching to fingolimod in the Italian study “was not influenced by a shorter washout [period] or a low lymphocyte count when alemtuzumab was started,” Dr. Frau said. A shorter washout period has been hypothesized to account for recent accounts of disease flares seen when switching from fingolimod to alemtuzumab, she explained.
Indeed, Dr. Frau noted that there had been a few studies that reported MS disease reactivation soon after the switch to alemtuzumab was made, which could be because lymphocytes remain in the lymph nodes when alemtuzumab is administered, this means that potentially they could repopulate the central nervous system and reactivate the disease.
However, “when alemtuzumab is started after fingolimod it is not a risk factor for reactivation of the disease,” Dr. Frau said, based on the current study’s findings.
As expected, the frequency of relapses increased during the washout period after stopping fingolimod, going from 12.7% of patients with relapse in the first month, 18.2% at 2 months, and 22.2% at 3 months. The time to first relapse from the start of alemtuzumab treatment was 6 months for 2.9% of patients, 9 months for 10.5% of patients, and 1 year for 20.7% of patients.
Asked to comment on when the optimal time to switch from fingolimod to alemtuzumab might be, Dr. Frau said: “The optimal time could be 1 month when the lymphocyte count is not too low.” However, lymphocyte counts were not measured in the entire cohort, so “these data perhaps need to have more strength.”
The switch from natalizumab to alemtuzumab
Other data on switching to alemtuzumab, this time from natalizumab (Tysabri), in the ANSWERS MS study were presented by Paul Gallagher, MBChB, of Queen Elizabeth University Hospital, London, and the University of Glasgow (Scotland).
ANSWERS MS (Alemtuzumab after Natalizumab Switch in Evolving Rapidly Severe MS) is a retrospective, observational analysis of routinely collected data on the use of alemtuzumab by 13 centers the United Kingdom and Ireland. These centers have been collecting data since before alemtuzumab was licensed in 2014 for MS, Dr. Gallagher observed, with some centers having experience of making the switch for more than a decade.
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.
BERLIN – Switching to alemtuzumab from fingolimod is associated with improved disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to the results of a real-world study reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Jessica Frau, MD, of the University of Cagliari (Italy) reported that a switch from fingolimod (Gilenya) to alemtuzumab (Lemtrada) in 77 patients treated at 11 Italian centers was able to “reduce dramatically disease activity in patients who did not respond to fingolimod.”
Dr. Frau reported: “When we compared in our cohort the last year of fingolimod with the first year after the first course of alemtuzumab, we found a significant decrease in the annualized relapse rate [ARR].” The ARRs were 0.60 for fingolimod and 0.20 after 1 year of alemtuzumab treatment.
“We found also a trend towards an improvement in the EDSS [Expanded Disability Status Scale] score (P = .23), and less evidence of disease activity on MRI, both in terms of new T2 lesions and gadolinium-enhancing (Gd+) lesions.”
The last MRI during fingolimod treatment showed new T2 and Gd+ enhancing lesions in 69.2% and 58.6% of patients, respectively. Corresponding figures for the first MRI during alemtuzumab treatment were 10.4% and 2.2% of patients.
The beneficial effects of switching to fingolimod in the Italian study “was not influenced by a shorter washout [period] or a low lymphocyte count when alemtuzumab was started,” Dr. Frau said. A shorter washout period has been hypothesized to account for recent accounts of disease flares seen when switching from fingolimod to alemtuzumab, she explained.
Indeed, Dr. Frau noted that there had been a few studies that reported MS disease reactivation soon after the switch to alemtuzumab was made, which could be because lymphocytes remain in the lymph nodes when alemtuzumab is administered, this means that potentially they could repopulate the central nervous system and reactivate the disease.
However, “when alemtuzumab is started after fingolimod it is not a risk factor for reactivation of the disease,” Dr. Frau said, based on the current study’s findings.
As expected, the frequency of relapses increased during the washout period after stopping fingolimod, going from 12.7% of patients with relapse in the first month, 18.2% at 2 months, and 22.2% at 3 months. The time to first relapse from the start of alemtuzumab treatment was 6 months for 2.9% of patients, 9 months for 10.5% of patients, and 1 year for 20.7% of patients.
Asked to comment on when the optimal time to switch from fingolimod to alemtuzumab might be, Dr. Frau said: “The optimal time could be 1 month when the lymphocyte count is not too low.” However, lymphocyte counts were not measured in the entire cohort, so “these data perhaps need to have more strength.”
The switch from natalizumab to alemtuzumab
Other data on switching to alemtuzumab, this time from natalizumab (Tysabri), in the ANSWERS MS study were presented by Paul Gallagher, MBChB, of Queen Elizabeth University Hospital, London, and the University of Glasgow (Scotland).
ANSWERS MS (Alemtuzumab after Natalizumab Switch in Evolving Rapidly Severe MS) is a retrospective, observational analysis of routinely collected data on the use of alemtuzumab by 13 centers the United Kingdom and Ireland. These centers have been collecting data since before alemtuzumab was licensed in 2014 for MS, Dr. Gallagher observed, with some centers having experience of making the switch for more than a decade.
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.
REPORTING FROM ECTRIMS 2018
Key clinical point: Good results can be achieved by switching from fingolimod or natalizumab to alemtuzumab in relapsing-remitting multiple sclerosis (RRMS).
Major finding: Annualized relapse rates were 0.60 for fingolimod at the time of the switch and 0.20 after 1 year of alemtuzumab treatment in one real-world study. In another, alemtuzumab was effective in reducing inflammatory disease activity when natalizumab failed.
Study details: Two real-world, observational studies: one with 77 RRMS patients treated at 11 Italian centers and the other a retrospective analysis of routinely collected data on 79 patients.
Disclosures: Dr. Frau disclosed that she serves on scientific advisory board for Biogen, Merck, and Genzyme and that she has received honoraria for speaking from Merck Serono, Genzyme, Biogen, and Teva. ANSWERS MS was funded by Sanofi-Genzyme. Dr. Gallagher disclosed he had received salary payment and travel funding for educational events from Sanofi-Genzyme and travel funding from Novartis and Biogen.
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.