Current research on type 1 diabetes (T1D) and islet cells often uses immunosuppressant drugs to prevent rejection of implanted cells. While some studies aim to reduce or even eliminate the need for these drugs, others only enroll participants who are already taking them, such as those with a previous kidney transplant. 

Engineering cells that can avoid attacks from the immune system altogether is a promising strategy. Still, immunosuppressant drugs are necessary in some studies. Despite their risks, they are essential in protecting implanted cells in select research. 

In an interview with T1D Exchange, Diana Isaacs, PharmD, CDCES, discusses the use of immunosuppressants in research focused on curative therapies for T1D. Keep reading to learn more. 

 

What are immunosuppressant medications, and how do they work? 

Diana Isaacs: Immunosuppressive drugs decrease the body’s immune response. They’re used for a variety of reasons. In this case, they target white blood cells, stopping them from increasing and attacking newly implanted insulin-producing cells, which can lead to their rejection.  

Normally, when there’s an infection or virus, the body initiates an immune response, which is beneficial because it helps fight off the illness. Keep in mind that these medications dampen the entire immune system and its healthy responses. So, when taking these types of medications, a person may be at increased risk of other types of infections.  

Common immunosuppressants include prednisone, dexamethasone, tacrolimus, sirolimus, and mycophenolate mofetil. There’s also a new drug under development called Tegoprubart, which may have fewer side effects than others.  

 

What are the potential side effects? 

Immunosuppressants can cause side effects beyond simply suppressing the immune system. These side effects can vary depending on the type of immunosuppressant drug that’s taken. 

For instance, corticosteroids are known to cause a variety of adverse effects, including increased glucose and blood pressure, weight gain, and other unwanted side effects like mood changes.  

It’s also important to note that Immunosuppressants can reduce the effectiveness of vaccines. That’s because a normal immune response is necessary for someone to gain the most from it. 

Moreover, the way many of these drugs are metabolized can potentially lead to drug interactions. In other words, if you’re prescribed an immunosuppressant, there’s an increased risk of issues with other drugs you may be taking.  

Even some common medications like statins are metabolized through the same pathways, so they’ll need to be adjusted, or you’ll need to be prescribed a new type of medicine to avoid toxic effects. Being aware of these potential interactions is important for safe treatment.   

 

How are some research studies decreasing the use of immunosuppressant drugs? 

Scientists are exploring ways to enclose (encapsulate) islet cells so the body will be less likely to attack and reject them. By enclosing cells, they are less likely to trigger an immune response, making it easier for the body to accept.   

One promising study was conducted without the use of immunosuppressive drugs. While this is the ultimate goal, ongoing studies are also looking at ways to minimize the use of these drugs or replacing them with less toxic ones.  

Ideally, we’ll reach a point where the body will not attack the cells, they’ll continue to produce insulin, and these lifelong drugs would not be needed. 

 

Why do researchers hope to use immunosuppressants for the shortest time intervals or avoid them altogether? 

Short-term risks associated with immunosuppression are very low. That’s why prednisone is commonly prescribed in this way for many different conditions. However, its long-term use can increase the risk of osteoporosis, blood-borne cancers, and other metabolic conditions.  

If you can use immunosuppressants for the short term, once you stop the medications, the risk of infections or other toxic effects on the kidneys or liver should generally resolve.  

That’s why reducing or eliminating the use of immunosuppressants is the goal. For example, a recent study on zimislecel involved participants who received steroid-free immunosuppressive therapy.  

 

Should I wear a medical alert if I’m taking immunosuppressant drugs? 

Yes. Let’s say you’re hospitalized, you don’t want to miss your immunosuppressant medication, because rejection can happen pretty quickly. That’s the really tough part. You can’t go long without them. 

Even with taking the meds perfectly on schedule, sometimes things can happen. 

If there’s a drug interaction, you may not fully absorb the immunosuppressant, which can increase your chance of rejection. Some medications need regular monitoring. For example, tacrolimus, a commonly used immunosuppressant, requires lab monitoring. 

That’s because we need to make sure the drug level isn’t too high, which can cause toxicity, and that it’s not too low, making it ineffective. They may also impact electrolytes like potassium and sodium, so it’s important to have lab work done.  

 

What is informed consent in research? 

All research must go through an institutional review board, or IRB. The IRB is generally meticulous about making sure that participants are informed of all of the risks that could occur with research. You’ll hear this referred to as “informed consent.” 

Typically, a research coordinator will contact participants and set up a meeting to review documents and discuss what to expect. This is your opportunity to ask any questions, and you can have multiple meetings to ask them. 

Ultimately, some people will choose to participate. Others may choose not to, depending on the risk, the time commitment, and other things they learn about the study.  

Certain trials are focused on people with extreme and unpredictable hypoglycemia. For those at risk of having these severe lows, participating in a study requiring immunosuppressant medications may be worthwhile.   

 

What would you say to someone who is on the fence about participating in research because of immunosuppressants? 

I think it’s fair — it’s a big decision. It’s important to know the timeline and risks of taking these medications, whether short- or long-term, and also to do research about the clinical trial itself. 

It’s also important to talk with the team to be sure you’re fully informed. Understandably, we want people to enroll in research to push progress forward — it’s the only way to ultimately get a cure. I think it’s a very individualized decision on what to do.

 

____________________________

Diana Isaacs, PharmD, BCPS, BCACP, CDCES, BC-ADM, FADCES, FCCP, is an Endocrine Clinical Pharmacist at the Cleveland Clinic. She advocates access and choice to the latest technologies and therapeutics for all people with diabetes and speaks on diabetes-related topics nationally and internationally. She was the 2020 ADCES Diabetes Care and Education Specialist of the Year.