WDC: Disease-modifying immunotherapy ‘the future of diabetes care’

VANCOUVER – Perhaps in the not-too-distant future, people at risk for type 1 diabetes will be screened for antibodies against beta cells, and, if two or more are present, started on immunotherapy to prevent beta cell destruction and clinical disease.

The vision is to treat “islet autoimmunity” as we do hypertension and other silent diseases to prevent problems down the road.

In the everyday medical world, that’s mostly science fiction for now – treatment starts when symptoms emerge – but researchers around the world are working hard to make it a reality, including Dr. Carla J. Greenbaum, director of the Diabetes Research Program at the Benaroya Research Institute in Seattle.

It’s known now that when babies have two or more antibodies against beta cells, about 11% per year will develop clinical diabetes, and all of them eventually. Adults with two or more antibodies will also develop diabetes, although at a slower rate than children.

“The take-home message is that type 1 diabetes starts when you have two antibodies. We need to change from symptom management to disease-modifying therapy, and that will require immunotherapy; it will be the future of diabetes care. Endocrinologists need to learn about immunotherapy,” Dr. Greenbaum said at the World Diabetes Congress.

So far, studies of four immunotherapies – teplizumab (Diabetes. 2013 Nov;62[11]:3766-74), rituximab (N Engl J Med. 2009 Nov 26;361[22]:2143-52), abatacept (Diabetes Care. 2014 Apr;37[4]:1069-75), and, most recently, alefacept (J Clin Invest. 2015 Aug 3;125[8]:3285-96) – have shown positive outcomes in preserving beta cell function after diagnosis of type 1. “The positive results are largely driven by children,” she said, suggesting that they might benefit most from a screen-and-treat approach to islet autoimmunity.

Teplizumab, oral insulin, and abatacept are now being tested in antibody-positive patients who haven’t developed symptoms. The trials aim to reduce the risk of clinical disease by 40%. If successful, treating 100 people with islet autoimmunity would prevent 14 from getting clinical type 1 diabetes, said Dr. Greenbaum, who is involved in the work.

A lot of questions need to be answered if the results pan out. Who should be screened, for instance, and how, and what immunotherapies should be used in different patient groups? What’s the right balance between risks and benefits?

There’s also a big question about how to “bring disease-modifying therapies to the clinic. As endocrinologists, we don’t use immunotherapies, but it’s important to recognize that millions of people for many decades have been using them safely to change the course of disease. We need to learn how to do this,” Dr. Greenbaum said.

“I often get people saying immunotherapy doesn’t really work, but that’s not true.” The effect sizes are small – maybe 20% – but it’s the same case in multiple sclerosis and rheumatoid arthritis. “The issue is if you have a weak joint, and you are 20% better, you feel it, but if beta cells are doing better, you might not notice,” she said.

Dr. Greenbaum disclosed research support from Novo Nordisk.

[email protected]

VANCOUVER – Perhaps in the not-too-distant future, people at risk for type 1 diabetes will be screened for antibodies against beta cells, and, if two or more are present, started on immunotherapy to prevent beta cell destruction and clinical disease.

The vision is to treat “islet autoimmunity” as we do hypertension and other silent diseases to prevent problems down the road.

In the everyday medical world, that’s mostly science fiction for now – treatment starts when symptoms emerge – but researchers around the world are working hard to make it a reality, including Dr. Carla J. Greenbaum, director of the Diabetes Research Program at the Benaroya Research Institute in Seattle.

It’s known now that when babies have two or more antibodies against beta cells, about 11% per year will develop clinical diabetes, and all of them eventually. Adults with two or more antibodies will also develop diabetes, although at a slower rate than children.

“The take-home message is that type 1 diabetes starts when you have two antibodies. We need to change from symptom management to disease-modifying therapy, and that will require immunotherapy; it will be the future of diabetes care. Endocrinologists need to learn about immunotherapy,” Dr. Greenbaum said at the World Diabetes Congress.

So far, studies of four immunotherapies – teplizumab (Diabetes. 2013 Nov;62[11]:3766-74), rituximab (N Engl J Med. 2009 Nov 26;361[22]:2143-52), abatacept (Diabetes Care. 2014 Apr;37[4]:1069-75), and, most recently, alefacept (J Clin Invest. 2015 Aug 3;125[8]:3285-96) – have shown positive outcomes in preserving beta cell function after diagnosis of type 1. “The positive results are largely driven by children,” she said, suggesting that they might benefit most from a screen-and-treat approach to islet autoimmunity.

Teplizumab, oral insulin, and abatacept are now being tested in antibody-positive patients who haven’t developed symptoms. The trials aim to reduce the risk of clinical disease by 40%. If successful, treating 100 people with islet autoimmunity would prevent 14 from getting clinical type 1 diabetes, said Dr. Greenbaum, who is involved in the work.

A lot of questions need to be answered if the results pan out. Who should be screened, for instance, and how, and what immunotherapies should be used in different patient groups? What’s the right balance between risks and benefits?

There’s also a big question about how to “bring disease-modifying therapies to the clinic. As endocrinologists, we don’t use immunotherapies, but it’s important to recognize that millions of people for many decades have been using them safely to change the course of disease. We need to learn how to do this,” Dr. Greenbaum said.

“I often get people saying immunotherapy doesn’t really work, but that’s not true.” The effect sizes are small – maybe 20% – but it’s the same case in multiple sclerosis and rheumatoid arthritis. “The issue is if you have a weak joint, and you are 20% better, you feel it, but if beta cells are doing better, you might not notice,” she said.

Dr. Greenbaum disclosed research support from Novo Nordisk.

[email protected]

VANCOUVER – Perhaps in the not-too-distant future, people at risk for type 1 diabetes will be screened for antibodies against beta cells, and, if two or more are present, started on immunotherapy to prevent beta cell destruction and clinical disease.

The vision is to treat “islet autoimmunity” as we do hypertension and other silent diseases to prevent problems down the road.

In the everyday medical world, that’s mostly science fiction for now – treatment starts when symptoms emerge – but researchers around the world are working hard to make it a reality, including Dr. Carla J. Greenbaum, director of the Diabetes Research Program at the Benaroya Research Institute in Seattle.

It’s known now that when babies have two or more antibodies against beta cells, about 11% per year will develop clinical diabetes, and all of them eventually. Adults with two or more antibodies will also develop diabetes, although at a slower rate than children.

“The take-home message is that type 1 diabetes starts when you have two antibodies. We need to change from symptom management to disease-modifying therapy, and that will require immunotherapy; it will be the future of diabetes care. Endocrinologists need to learn about immunotherapy,” Dr. Greenbaum said at the World Diabetes Congress.

So far, studies of four immunotherapies – teplizumab (Diabetes. 2013 Nov;62[11]:3766-74), rituximab (N Engl J Med. 2009 Nov 26;361[22]:2143-52), abatacept (Diabetes Care. 2014 Apr;37[4]:1069-75), and, most recently, alefacept (J Clin Invest. 2015 Aug 3;125[8]:3285-96) – have shown positive outcomes in preserving beta cell function after diagnosis of type 1. “The positive results are largely driven by children,” she said, suggesting that they might benefit most from a screen-and-treat approach to islet autoimmunity.

Teplizumab, oral insulin, and abatacept are now being tested in antibody-positive patients who haven’t developed symptoms. The trials aim to reduce the risk of clinical disease by 40%. If successful, treating 100 people with islet autoimmunity would prevent 14 from getting clinical type 1 diabetes, said Dr. Greenbaum, who is involved in the work.

A lot of questions need to be answered if the results pan out. Who should be screened, for instance, and how, and what immunotherapies should be used in different patient groups? What’s the right balance between risks and benefits?

There’s also a big question about how to “bring disease-modifying therapies to the clinic. As endocrinologists, we don’t use immunotherapies, but it’s important to recognize that millions of people for many decades have been using them safely to change the course of disease. We need to learn how to do this,” Dr. Greenbaum said.

“I often get people saying immunotherapy doesn’t really work, but that’s not true.” The effect sizes are small – maybe 20% – but it’s the same case in multiple sclerosis and rheumatoid arthritis. “The issue is if you have a weak joint, and you are 20% better, you feel it, but if beta cells are doing better, you might not notice,” she said.

Dr. Greenbaum disclosed research support from Novo Nordisk.

[email protected]