Purine Antimetabolite Therapy for RRMS


Characteristics that make the purine antimetabolite, cladribine, a unique treatment option for relapsing-remitting multiple sclerosis.

Jennifer Graves, MD, PhD, MAS: Dr Shah, do you want to tell us a little about the periodic oral medication that we use in MS [multiple sclerosis], cladribine [Mavenclad]?

Suma Shah, MD: Yes. This is a different type of oral medication in our world. Cladribine has also been around for years, similar to teriflunomide [Aubagio]. I have patients who were oncology nurses in the early 1990s who were giving it IV [intravenously]. Most recently, it was approved at total standard doses that are weight-based at 3.5 mg/kg given over 2 weeks in year 1 and over 2 weeks in year 2, with the idea of it being an induction therapy. It’s highly effective. It interferes with DNA repair and as a result takes B cells and T cells out of circulating the immune system. For that reason, there are a couple of things to take into consideration about it.

Because of its strength and the way it works, there’s a bit of immune suppression that occurs in the first few months after taking it, which tends to reset after about 3 months. In addition to that, especially as we talk about pregnancy planning, it’s induction therapy and approved for those 2 years of use. That leaves some questions about what to do and how we should monitor patients after that second year of treatment. That makes it a great option for folks who may be considering pregnancy a couple of years down the line but not right away as something that can be done as an induction and then followed out to see how the patient does.

Jennifer Graves, MD, PhD, MAS: Thank you. Dr Macaron, since this is a unique category of oral medications, do you want to add anything to that?

Gabrielle Macaron, MD: It’s worth mentioning the ORACLE-MS trial because it tested cladribine in patients with CIS [clinically isolated syndrome], and the primary outcome was the time to develop clinically definite MS. Cladribine was also efficient in doing that. It reduces the proportion of patients with clinically definite MS. Basically, those are patients who had their first MS attack, and it prevented a second attack or new lesions. It’s highly effective. It was effective in reducing MRI activity by approximately 90%.

The main adverse events are infections, but mainly upper respiratory tract infection, zoster, and malignancy. One of the scary parts about cladribine for many years, especially in the 1990s when there was a trial on the parenteral version of cladribine, was the risk of malignancies in the long run. In CLARITY [clinical trial], there was a higher proportion of patients who had malignancies on cladribine than placebo, but long-term data and extension studies suggest that this risk isn’t much higher. That’s quite reassuring for us to use this medication more frequently in patients.

Jennifer Graves, MD, PhD, MAS: Thank you for watching this NeurologyLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.

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