ACTH: A Nonsystemic Steroid Alternative in Relapsing MS

Regina Berkovich, MD, PhD: Lately, a lot of attention has been given to the function of the B lymphocytes in multiple sclerosis. I must say that evidence of the reaction of B cells to the melanocortin active compounds or biologicals such as ACTH [adrenocorticotropic hormone] goes back to the 1980s. I’m not aware of any newer publications, but it would be extremely interesting to reproduce those old studies and see what we can establish in the immunology these days. What was shown back in the ’80s is that the effect is more regulatory rather than suppressive. That may be very interesting in this new era of us dealing with therapies with profound B-cell depletion.

ACTH, unlike the systemic steroids, did show evidence of activation of immunoglobulin production and activation of differentiation of the B cells, which is quite unexpected when we think about systemic hormones. Again, that acts as proof of the previous statement that it’s a regulatory hormone. When we say regulatory, it means that it may suppress the response, when necessary, but it may actually support the response and make it more evident, depending on the different circumstances. With the steroids, we mostly expect to see a suppression of the humeral response. This is actually why steroids are broadly used in the B-cell—driven conditions.

Again, I would like to say that systemic steroids are the first-line therapy because of their robustness, availability, and financial accessibility. Clearly, we all are quite comfortable with methylprednisolone administration. The use of the ACTH is mostly reserved for those cases in which we cannot use the systemic steroids. Therefore, some of the comparisons between steroids and ACTH, in terms of price and efficacy, really don’t seem to be hitting the target. At least in my practice, I’m never expecting a competition between the 2. I’m using and ordering the ACTH when I’m restricted with the systemic steroids and when systemic steroids are unfortunately not an option. In that situation, I’m considering ACTH versus hospital admission for the plasma exchange, so that is where the comparison is going. Therefore, I think it’s important to remember that it’s a second-line therapy or a third-line therapy. By definition, it means that other therapies, either tried before or contraindicated, did not show efficacy. This is a limited population of patients we’re talking about. That’s why comparison doesn’t seem to be correct.

The additional studies would be very important to show how they compare. Some of the studies do exist. Again, we’re going back to late 1980s, when the steroids were compared with the ACTH, and efficacy did not show a significant difference. Intravenous [IV] methylprednisolone given at 1 g did not show superiority with respect to the effects in the treatment of MS relapse. That’s the Alan Thompson study. However, we do see in that study, as well as in our clinical practice, the evidence of a more robust response. With the steroids, you can expect more robust response, while ACTH may take longer to be clinically appreciated.

When it comes to the dosages, I would like to point out that in the classic James Rose study, the dosages of ACTH were used for a much longer period of time than we practically use today. Back then it was used for 2 to 3 weeks. Right now, my experience and my clinical recommendation would be to consider between 5 and 15 days. We’re talking about 1, 2, or on rare occasions 3 vials, because 1 vial is 5 mL and good for five 1-mL daily injections. It certainly can be used on a daily basis. Those patients who would need it for every other day for various reasons can do that as well. That can be decided clinically on individual basis.

It’s important to note that studies were done, and publications are out there showing that 5 days and the use of 5 mL total can be efficacious for MS relapses. My clinical experience has been that it may not be sufficient for the majority of MS-relapsing patients, and it may need to be extended to 7 to 10 days. I rarely ever use more than 10 days for MS relapse treatment when it comes to the ACTH. In a nutshell, I use it for 5 to 15 days, and usually 10. My experience has been with giving 1 cc intramuscularly. There is evidence that it works just the same with respect to the bioavailability and pharmacokinetics when it comes to the subcutaneous injections. It can be used intramuscularly or subcutaneously once a day.