The initial treatment of early active relapsing remitting MS should be with a potent induction therapy rather standard immunomodulation then escalation
Author(s):
G. Edan
G. Edan
Affiliations:
ECTRIMS Online Library. Edan G. 09/14/16; 146950; 68
Gilles Edan
Gilles Edan
Contributions
Abstract

Abstract: 68

Type: Oral

There are two contrasting treatment regimens in MS : induction versus escalation

The rationale behind escalating therapy is that treatment starts with safe drugs and only moves on to more aggressive ones if the ongoing treatment fails. . In the escalating approach ,interferon betas, glatiramer acetate, , teriflunomide and BG12 are regarded as first-line drugs, and immunosuppressants (mitoxantrone, natalizumab, fingolimod, alemtuzumab, ocrelizumab ) as second-line ones, and very intensive immunosuppression (autologous bone marrow transplantation, high-dose cyclophosphamide) as third-line ones.

The key to the success of escalation therapy is to define upfront with the patient the exact suboptimal response threshold at which the next-level therapeutic option should be introduced. Given that all the immunosuppressants that are currently available present potentially serious side effects, the induction strategy has generally been reserved for patients with very active and aggressive disease. In these patients, there is an acknowledged risk of early disability, and once neurological function is lost, it cannot be regained. This disease-inherent risk can be assumed to outweigh that associated with the use of powerful immunosuppressants. This treatment strategy involves the use of immunosuppressants for the minimum amount of time needed to gain adequate control over disease activity. Once disease control has been achieved, treatment can be switched to maintenance therapy with a better tolerated drug. A randomised study have demonstrated that induction with mitoxantrone followed by maintenance treatment affords better disease control than monotherapy with an interferon beta. Natalizumab is also effective, but has a propensity to result in rebound inflammatory disease activity on withdrawal. More recently, a mere 5-day course of intravenous perfusions of alemtuzumab was found to bring long-term clinical benefits in early relapsing MS patients. This approach may be a useful and conservative means of using these highly effective therapies whilst minimising exposure and the attendant safety risk.

Disclosure: Dr. Edan reports grants and personal fees from Bayer, Merck , Teva Pharma, Novartis , personal fees from Biogenidec, Sanofi , LFB.

Abstract: 68

Type: Oral

There are two contrasting treatment regimens in MS : induction versus escalation

The rationale behind escalating therapy is that treatment starts with safe drugs and only moves on to more aggressive ones if the ongoing treatment fails. . In the escalating approach ,interferon betas, glatiramer acetate, , teriflunomide and BG12 are regarded as first-line drugs, and immunosuppressants (mitoxantrone, natalizumab, fingolimod, alemtuzumab, ocrelizumab ) as second-line ones, and very intensive immunosuppression (autologous bone marrow transplantation, high-dose cyclophosphamide) as third-line ones.

The key to the success of escalation therapy is to define upfront with the patient the exact suboptimal response threshold at which the next-level therapeutic option should be introduced. Given that all the immunosuppressants that are currently available present potentially serious side effects, the induction strategy has generally been reserved for patients with very active and aggressive disease. In these patients, there is an acknowledged risk of early disability, and once neurological function is lost, it cannot be regained. This disease-inherent risk can be assumed to outweigh that associated with the use of powerful immunosuppressants. This treatment strategy involves the use of immunosuppressants for the minimum amount of time needed to gain adequate control over disease activity. Once disease control has been achieved, treatment can be switched to maintenance therapy with a better tolerated drug. A randomised study have demonstrated that induction with mitoxantrone followed by maintenance treatment affords better disease control than monotherapy with an interferon beta. Natalizumab is also effective, but has a propensity to result in rebound inflammatory disease activity on withdrawal. More recently, a mere 5-day course of intravenous perfusions of alemtuzumab was found to bring long-term clinical benefits in early relapsing MS patients. This approach may be a useful and conservative means of using these highly effective therapies whilst minimising exposure and the attendant safety risk.

Disclosure: Dr. Edan reports grants and personal fees from Bayer, Merck , Teva Pharma, Novartis , personal fees from Biogenidec, Sanofi , LFB.

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