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Steroid-Sparing Therapies for Autoimmune Disease


Rationale for controlling autoimmune disorder inflammation with steroid-sparing therapies such as immunomodulators and biologics.

Transcript

Marla Dubinsky, MD: The next category of drugs includes immunomodulators. They probably were touted as the most important steroid-sparing strategy from 1980 until 1998, specifically mercaptopurine and azathioprine. They remain a very important part of practice. However, the data do not really support their use in Crohn disease because they haven’t really shown that they change the natural history as much as we may have thought they did.

As monotherapy, meaning in the absence of combining them with something else, I think they are losing momentum in most parts of North America. But in Europe, for cost reasons, they are actually a lot less expensive than the biologic-based strategies. So based on your healthcare system, the step-up approach of using an anti-inflammatory is often driven by cost. The biologics are clearly more expensive than the immunomodulators that have been around for a long time.

However, there is a safety concern with immunomodulators, particularly in people who are above the age of 60 or 65. In these patients, there’s an increased risk of lymphoma. In patients under the age of 25, especially males, with these thiopurines—6-MP [6-mercaptopurine] or azathioprine—there’s an increased risk of lymphoma. One that’s of particular concern to the younger age group is something called hepatosplenic T-cell lymphoma, which is universally fatal. That was initially found when thiopurines were combined with anti-TNF [tumor necrosis factor] therapy. Everyone thought it was the TNF, and there’s a big black box warning around all the anti-TNFs talking about this lymphoma. But to be truthful, we dug a little deeper, especially in children because that was where the first 6 cases were really thought to be—pediatric only. But now there are more than 6 cases, and most of them are not of pediatric onset. They’re younger, but it could occur in anybody whom an adult or pediatric gastroenterologist would treat.

When we dug a little deeper, we realized that the risk of malignancy, particularly in children, was tied to the combination of thiopurines plus TNF or thiopurines alone, not anti-TNF alone. So we have a difficult job when we’re managing adults or young adolescents, especially males. There’s a big black box warning that talks particularly about young adolescent males. We dissected that, and we try to work on the idea that this is because of the combination and not because of the anti-TNF alone. This was a revolution to me. The concept of the importance of biologics rose because we started to see some risk factors with thiopurines, not only with TNF but alone.

Methotrexate is also considered to be an immunomodulator. That sort of gained a lot of popularity after this lymphoma started to pop up with the use of thiopurines. People were using methotrexate instead, again, often in combination with an anti-TNF. The whole reason for the combination appears to be tied to the fact that biologics, particularly anti-TNFs, can be cleared quickly through the body. So it’s based on their pharmacokinetics. These 2 drugs could actually help increase the drug level, or drug concentration, to help keep the TNF working longer and make it more durable. So they are companions, but there are new strategies to do that with the anti-TNFs where you don’t need the second drug.



Episode #1

Pathophysiology of Autoimmune Diseases and Inflammation
Pathophysiology of Autoimmune Diseases and Inflammation

Episode #2

Distinguishing Between Autoimmune Conditions: IBD
Distinguishing Between Autoimmune Conditions: IBD

Episode #3

Factors and Exposures Linked to Autoimmune Diseases
Factors and Exposures Linked to Autoimmune Diseases

Episode #4

Accurately Diagnosing an Autoimmune Disease
Accurately Diagnosing an Autoimmune Disease

Episode #5

Nonbiologic Therapy for Autoimmune Diseases
Nonbiologic Therapy for Autoimmune Diseases

Episode #6

Steroid-Sparing Therapies for Autoimmune Disease
Steroid-Sparing Therapies for Autoimmune Disease

Episode #7

Biologics and Small Molecules for Autoimmune Diseases
Biologics and Small Molecules for Autoimmune Diseases

Episode #8

TNF Inhibitors: Patient Selection
TNF Inhibitors: Patient Selection

Episode #9

Relationship Between Pregnancy and Autoimmune Disease
Relationship Between Pregnancy and Autoimmune Disease

Episode #10

Biologic Therapies and Pregnancy: Inflammation Control
Biologic Therapies and Pregnancy: Inflammation Control

Episode #11

Discontinuing/Switching of Biologics During Pregnancy
Discontinuing/Switching of Biologics During Pregnancy

Episode #12

Counseling Patients on Inflammation Control and Pregnancy
Counseling Patients on Inflammation Control and Pregnancy

Episode #13

Advances in Inflammation Control Throughout Pregnancy
Advances in Inflammation Control Throughout Pregnancy

Episode #14

A Clinical Background on Autoimmune Disease
A Clinical Background on Autoimmune Disease

Episode #15

Treatment Considerations and Autoimmune Disease
Treatment Considerations and Autoimmune Disease

Episode #16

TNF Inhibitors and Autoimmune Disease
TNF Inhibitors and Autoimmune Disease

Episode #17

Pregnancy and Autoimmune Disease
Pregnancy and Autoimmune Disease

Episode #18

Treatment Considerations for Childbearing and Autoimmune Disease
Treatment Considerations for Childbearing and Autoimmune Disease

Episode #19

Managing Autoimmune Disease Post Partum
Managing Autoimmune Disease Post Partum
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