Why escalation therapy is the preferred principle over treatment induction
ECTRIMS Online Library. Waubant E. 09/13/19; 279560; 301
Emmanuelle Waubant
Emmanuelle Waubant
Contributions
Abstract

Abstract: 301

Type: Scientific Session

Abstract Category: Scientific Session 15: How to optimise long term benefit of MS treat

E. Waubant

Neurology, UCSF, San Francisco, CA, United States

The availability of a broad range of disease-modifying drugs with a large spectrum of effectiveness and mode of administration questions best treatment strategy. A more conservative algorithm consists in starting with therapies that have a lower impact on risk of relapse and subsequently escalade if needed. This is especially relevant considering available data showing overall slower disability progression in large cohorts of treated patients than in past studies performed in untreated individuals. This escalation strategy is now challenged by the increased availability of drugs with higher efficacy. Drugs that have a modest effect on disease course on average can in fact control very well clinical and MRI activity in some individuals, with an excellent long-term safety profile. Some of the newer highly effective treatment strategies for MS may alter or suppress the immune response in a more dramatic way. As such, they have been associated with a higher risk of opportunistic infections, or severe autoimmune disorders, some of which have been fatal. In addition, the long-term safety of these newer treatment strategies remains to be determined as overall modest numbers of patients have been exposed worldwide for limited periods of time. Furthermore, some strategies such as bone marrow transplant have mostly been studied without a consistent control group. Virtually no large trial of induction therapy has been completed in MS, but several are ongoing. As such, it is unclear if the more potent agents that could be used for induction early in disease course are superior to an escalation strategy in terms of long-term effectiveness and safety. Finally, very few available MS treatments alter the immune response in a way that would provide true induction, i.e. prolonged remission after drug discontinuation. Considering the lack of existing evidence, we should not consider potent induction early in the disease course for most patients, but rather await the completion of the ongoing well-designed trials of induction so we can put this debate to rest.
Disclosure: Waubant: Nothing to disclose.

Abstract: 301

Type: Scientific Session

Abstract Category: Scientific Session 15: How to optimise long term benefit of MS treat

E. Waubant

Neurology, UCSF, San Francisco, CA, United States

The availability of a broad range of disease-modifying drugs with a large spectrum of effectiveness and mode of administration questions best treatment strategy. A more conservative algorithm consists in starting with therapies that have a lower impact on risk of relapse and subsequently escalade if needed. This is especially relevant considering available data showing overall slower disability progression in large cohorts of treated patients than in past studies performed in untreated individuals. This escalation strategy is now challenged by the increased availability of drugs with higher efficacy. Drugs that have a modest effect on disease course on average can in fact control very well clinical and MRI activity in some individuals, with an excellent long-term safety profile. Some of the newer highly effective treatment strategies for MS may alter or suppress the immune response in a more dramatic way. As such, they have been associated with a higher risk of opportunistic infections, or severe autoimmune disorders, some of which have been fatal. In addition, the long-term safety of these newer treatment strategies remains to be determined as overall modest numbers of patients have been exposed worldwide for limited periods of time. Furthermore, some strategies such as bone marrow transplant have mostly been studied without a consistent control group. Virtually no large trial of induction therapy has been completed in MS, but several are ongoing. As such, it is unclear if the more potent agents that could be used for induction early in disease course are superior to an escalation strategy in terms of long-term effectiveness and safety. Finally, very few available MS treatments alter the immune response in a way that would provide true induction, i.e. prolonged remission after drug discontinuation. Considering the lack of existing evidence, we should not consider potent induction early in the disease course for most patients, but rather await the completion of the ongoing well-designed trials of induction so we can put this debate to rest.
Disclosure: Waubant: Nothing to disclose.

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