Treatment of Multiple Sclerosis Relapses - Episode 11
Thomas P. Leist, MD, PhD: As we discussed earlier on, when we have a relapse, there is a tendency to use steroids. Another approach to using steroids would be to induce endogenous steroids by using ACTH [adrenocorticotropic hormone]. It has been proposed that the use of ACTH in its current commercial formulations may be a potential alternative to using steroids in patients that are either intolerant or resistant to steroids. Additional information is needed on these matters. ACTH is an agent that was available for a long time before steroids were used for the treatment of MS [multiple sclerosis] attacks. At this time, we have steroids available, and we also have plasma exchange available. ACTH may line itself up with those, depending on its local availability for patients that have experienced attacks that are resistant to steroids.
ACTH, or adrenocorticotropin, is an agent that induces secretion of steroids, as well as other downstream mechanisms. The idea is that it may potentially form a mode of action that is distinct from that of steroids alone. Much of this discussion is from a more academic point of view. Head-to-head trials to look at whether responses to ACTH are superior compared to steroids have not been performed. At this point in time, currently marketed forms of ACTH are probably a second-line approach versus steroids that are available.
Steroid-based medications may affect B-cells and T-cells due to the fact that they can lead to apoptosis. It is thought that this effect is also extended to ACTH, as it induces steroid secretion and the secretion of other regulatory factors that may affect B-cells and T-cells. Much of this investigation is based on in vitro and animal research, and has not been formally proven in humans.
In my practice, ACTH is used in patients that have failed to respond to or have allergies to steroids. It’s difficult to think of having patients with allergies to steroids, but there are patients that have multiple steroid allergies. I also use it in patients with other autoimmune diseases such as type 1 diabetes, where the use of steroids may complicate the management of the underlying disease. I normally use a 5-day course repeated twice, or a total of 10 days in those patients.
When we think of treatment of relapses, we first think of steroids. However, it is important to keep in mind that before steroids were the standard of treatment in MS relapses, we actually used ACTH. ACTH remains available for the treatment of attacks. Obviously, at this point in time we very often first reach to steroids in order to treat the patients. Some of the reasons for this may have fiscal and financial or coverage consideration as an underpinning. Keep in mind that ACTH raises endogenous steroid levels as well as levels of other regulatory factors. This remains an option to be considered in patients where regular treatment with steroids is an issue. The treatment of relapses may also include plasma exchange. Unfortunately, plasma exchange is only available in certain specialized centers and is not available to the larger population outside of centers that have appropriate units to do so.