Systemic Steroids vs ACTH in Relapsing MS

Regina Berkovich, MD, PhD: The use of ACTH [adrenocorticotropic hormone] certainly is reserved by its FDA approved indication. It is approved for MS [multiple sclerosis] relapses, therefore we use it in a setting of any relapsing form, including relapsing-remitting MS, for the acute treatment of MS exacerbation. That is the approved indication, and this is where we use it. Again, we use it rarely, if ever, as a first-line therapy. This is due to the financial differences between the coverage of systemic steroids and ACTH. ACTH is a much more expensive option. Therefore, systemic steroids remain as the first line of therapy, and this is supported with excellent experience and a robust response to the steroids. ACTH is reserved for those options or situations when systemic steroids are not feasible, contraindicated, or failed previously. More frequently, for patients who have intolerable life-threatening adverse effects such as, steroid-induced acute psychosis. That would be the most vivid presentation of preference of using ACTH.

I would like to point out that sometimes it has been noticed that the list of potential adverse effects of ACTH resembles the list of potential adverse effects of the systemic steroids. Again, the information comes from the 1970s at a time of approval when the concept and understanding of the ACTH mechanism and clinical efficacy were coming entirely from the steroidogenic effects. Steroids, like the production of cortisol, is only a minor part of how ACTH really works. To support this, I would like to point out there was a very important study done in the 1990s when the anti-inflammatory effects of ACTH were evaluated on adrenalectomized animals. Animals without adrenal glands were unable to produce cortisol, obviously, but still were able to show strong anti-inflammatory effects of ACTH in the absence of steroid-producing adrenal glands. It’s very interesting and important to remember. ACTH has its own direct anti-inflammatory effects.

However, when you look at the list of adverse effects, you may get an impression that they are the same. Methylprednisolone and ACTH have the same list of psychiatric adverse effects…. However, when it comes to the equivalent production of cortisol as a result of the stimulation of ACTH, that production is less than 3% compared to the 1 g Solu-Medrol. So you may expect the potential steroidogenic adverse effects to be just a fraction of what has been experienced in the setting of the systemic steroid use. That has been supported by my clinical experience. So those patients who, for example, had acute psychosis as an adverse effect of the systemic steroids did not have a similar reaction in my practice when ACTH was used.