Treatment for Obesity and Inflammation, but at what Cost?

Hello, I'm Jonathan K from UMass Chan Medical School in Worcester, Massachusetts. Today, I'd like to talk about the obesity epidemic that we face in the United States. About 40% of adults in the United States have a body mass index of greater than 30 and are considered to be obese and 9% have a body mass index of greater than 40 and are considered to have severe obesity.

Now this affects patients with rheumatic diseases. About 20% of patients with rheumatoid arthritis are obese and about 35% of patients with psoriatic arthritis are obese. Obesity also contributes to other rheumatologic conditions. Fibromyalgia can result from sleep disorders and obstructive sleep apnea is a consequence of obesity. Also osteoarthritis certainly results from the increased force applied across lower extremity joints. So the rheumatologic diseases are increased in patients with obesity and also comorbidities of inflammation. Inflammation associated with psoriasis, psoriatic arthritis and rheumatoid arthritis have an increased risk of cardiovascular disease. And cardiovascular risk is also exacerbated by obesity.

So the treatments for obesity have traditionally been diet although that's somewhat difficult to adhere to. It takes a lot of willpower. Bariatric surgery used to be relatively common among patients with severe obesity. But now with the introduction of incretin therapy GLP-1 agonists very few patients seem to undergo bariatric surgery and many many individuals are now taking GLP-1 agonists.

Now GLP-1 agonists have a number of effects besides weight loss. They were first studied and approved for treatment of type 2 diabetes mellitus because they lower blood glucose. They also lower serum lipids. They lower blood pressure. They decrease the risk of death due to cardiovascular disease. They decrease the risk of death due to obesity associated malignancies and they interestingly decrease the desire for alcohol. There was a study that was done where patients who are alcoholics were placed in a room for 2 hours with their favorite beverages. One group was treated with GLP-1 agonist. The other group was on placebo. And those who were treated with the GLP-1 agonist didn't touch the alcoholic beverages whereas those who were on placebo binged.

Also in addition to decreasing the desire for alcohol, incretins decrease the desire for food and result in weight reduction. They're catabolic so that not only do you lose weight but you also lose muscle mass. So it's important for individuals taking GLP-1 agonists to take additional protein supplementation of about 90 g a day.

Now in addition to these remarkable effects on reducing weight and other factors that are contributing to disease, GLP-1 agonists also have anti-inflammatory effects. T cells have receptors for GLP-1 agonists and there's direct binding of GLP-1 agonists to T cells that decrease T-cell mediated inflammation.

Also clinically, in a study, the STEP 9 study, in patients with knee osteoarthritis with elevated BMI, treatment with semaglutide reduced pain and also resulted in weight loss. And finally in a study of tirzepatide, another GLP-1 agonist, in combination with ixekizumab compared to ixekizumab alone, patients with psoriatic arthritis and a body mass index of about 35 kilograms per meter squared had improvement in overall psoriatic arthritis disease activity, tender joints, swollen joints, and improved significantly.

So one can use a GLP-1 agonist off label as an adjunct to DMARD therapy in patients with diseases such as psoriatic arthritis. Since they've become available, I've recommended to a number of my patients that they consider taking a GLP-1 agonist, patients who are obese with a body mass index of greater than 33 kg per meter squared, and especially those with comorbidities such as obstructive sleep apnea, type 2 diabetes, and psoriatic arthritis. Patients have noted greater response to their DMARD than without the GLP-1 agonist.

In addition to those patients who are obese, there are some patients who are inadequately responsive to their DMARD. I had a patient with peripheral spondyloarthritis who had normal body weight but who was inadequately responsive to secukinumab 300 milligrams taken subcutaneously monthly. I recommended to her that she obtain tirzepatide at the lowest dose 2.5 milligrams subcutaneously weekly which she added to her secukinumab therapy and whereas previously she had not responded adequately to secukinumab and several other biologic DMARDs before that, with the addition of low dose tirzepatide she finally responded to secukinumab. So we should think about looking into the adjunct use of an incretin in addition to DMARD therapy in patients with refractory disease.

The big problem is that nowadays because of the tremendous uptake of GLP-1 agonist therapy, many insurance providers no longer cover them for other than type 2 diabetes mellitus and
moderate to severe obstructive sleep apnea. So as a result, patients have to pay out of pocket for this medication. At the lowest doses, it's about $250 a month, but at doses above five milligrams subcutaneously weekly, the cost for tirzepatide is about $450 per month. Now, this is out of reach for many patients, and the cost of GLP-1 agonists must come down in order to make these very successful treatments available to the majority of patients who need them.

With this epidemic of obesity and its contribution to rheumatic diseases, we now have a very effective medication which has anti-inflammatory properties as well as all of the other properties of GLP-1 agonists. But this medication is not accessible to many patients because of its cost. I look forward to seeing the cost of GLP-1 agonists come down as the use continues to increase and look forward to following this field with great interest.

For more about this and other topics, go to RheumNow.com. I'm Jonathan K.