How Do Biologics Treat RA?


Biologics are a key component of treatment for people with rheumatoid arthritis, but how they actually work in the body can be a complex and confusing topic. Dr. Dana Jerome, the division head of rheumatology at Women’s College Hospital in Toronto, and Dr. Chris Morris, a rheumatologist at the Arthritis Associates of Kingsport, TN, answered our questions about biologics and how they work.

What are biologics?** Dr. Jerome:** Biologics are medications that have been developed based on what we know about how inflammatory diseases work. Once scientists were able to understand which molecules were particularly problematic in the process of RA and other inflammatory diseases, medications were developed to specifically target these molecules. Unlike previous treatments, such as traditional disease modifying drugs or DMARDs, which broadly suppress the immune system, these medications are very targeted.

Dr. Morris: Biologic treatments are products that are generally protein in nature and very similar to what our body might produce, or what our cells might produce. They’re made by living cells, act against either certain chemical signals that our body uses to activate inflammation, or they actually go against the inflammatory cells themselves.

How do they work to treat RA?** Dr. Jerome:** The first group of biologics that came onto the market inhibit a molecule called Tumor Necrosis Factor-alpha (TNF-alpha). These work by blocking the effect of the TNF-a. There are now five different medications available that work to block this molecule. Newer biologic medications have come out that block different parts of the immune system. Other medications work on B-cells, T-cell stimulation and another inflammatory molecule called interleukin-6 (IL-6).

Dr. Morris: One form (abatacept or Orencia) blocks the activation of the inflammatory cells by jamming the lock, if you will. What happens is there are a bunch of inflammatory white cells that are involved and one set of them needs a double signal to become active—those T-cells are activated by a stimulator plus a co-stimulator. I always describe it as like when you go in and get a lockbox at the bank—you have your key and the bank has its key. This blocks one of the two keys.

How are the different types of biologics administered?** Dr. Jerome:** Most of the biologics have to be taken either by an injection underneath the skin (subcutaneous), such as with Humira, or by an intravenous infusion.

What are the common side effects?** Dr. Jerome:** The most common side effect seen in patients taking biologics by injection is rash/redness or pain in the area where the injection is given.  Occasionally, patients who get their biologic medication through an IV infusion may experience flu-like symptoms, nausea or headache at the time of the infusion.

It’s important that all patients starting biologics get checked for the presence of inactive tuberculosis. These medications won’t cause TB, but sometimes TB can sit inactive in a patient’s lung and never cause a problem until they take a biologic medication. These medications may reactivate TB in someone who has already been exposed. If there is no exposure (normal chest x-ray and negative TB skin test) there should be no concern about this happening.

We always worry about infections in patients taking biologic medications. Upper respiratory infections, or sinus infections, are a fairly common side effect. Serious infections are rare on these medications, but can occasionally occur. If you’re on a biologic medication and get a fever, or think you may have an infection, speak to your doctor right away."¨Other common side effects may include feeling slightly queasy and fatigued for a day or two after treatment. These and other side effects are often manageable.

What is the difference between the biologics currently on the market? Is there a difference in how effective they are?** Dr. Jerome:** There are lots of different biologics currently on the market. The most common group is the TNF-a inhibitors. The big difference within this group is the way in which the medication is administered (IV, injection or tablet), the frequency with which the medication is taken (for instance, weekly, every two weeks or even monthly) and where they block the immune system. Generally, they are thought to be equally effective in the treatment of RA.

Why do some biologics work for some people, but not others?** Dr. Morris:** In RA, it isn’t that A causes B causes C. I think it is a cascade, and there are multiple pathways for a common end result. I also think there are certain pathways that seem more active in certain patients. There are patients who do well with TNF drugs and do horribly with other medicines. There are patients who do awful with TNF drugs, but do great with drugs that act on Interleukin-6, such as Actemra. The problem is that we really don’t have a good way of looking at a patient when they walk in the office and know which medicine is going to be the best.

How do you know when a biologic is working?** Dr. Jerome:** There are several goals that we have in mind when using any medication to treat RA. We would consider a treatment successful if the patient reaches a state of remission (meaning no tender or swollen joints) or a state of low disease activity. We are also treating patients in the hopes that we can prevent damage that can sometimes happen when inflammation persists in the joints. We have many good treatments available these days so these goals are very achievable in many patients.

How do you know when a medication is not managing your disease well? When should you switch?** Dr. Jerome:** When a patient goes to see his rheumatologist, a number of factors are assessed to determine how well he is doing. This includes gathering patient information, such as how much pain and stiffness they may be experiencing, and also some factors based on the doctor’s exam, such as the number of tender and swollen joints. Factors such as inflammatory markers seen on blood tests and even features based on x-rays go into this assessment.

As doctors, we want patients to be as well as possible and this means possibly changing, adding or removing treatments until the best "recipe" is found. If there is still a lot of joint swelling, a lot of pain and stiffness, or if there is progression of the disease on x-rays, usually the doctor will discuss a change in treatment.

Dr. Morris: These biologic products are proteins, but they are not made by our system. That means patients can make antibodies, which are our own bodies’ natural defenses. The body sees them as foreign, so some patients can develop antibodies that actually block that protein. This is one of the reasons why it’s important to see a patient regularly when they’re on a biologic. We want to ensure that the medicine is still working. We don’t want them wasting their money, and we also want to try and find something to get the disease under control.

How have the biologics changed treatment of RA?** Dr. Jerome:** For many years there were only a handful of medications available to treat RA. Many of these had a long list of side effects. The biologic medications, as well as research that shows treating RA early is very important, have really changed our goals in treating patients. We want to treat patients early and make the disease go into remission as much as we can. The biologics have dramatically increased our ability to do this. These medications work quickly, and for the most part are well tolerated.  There are so many good options for treatment now that didn’t exist even a few years ago.

Dr. Morris: With the advent of these medicines, patients are living longer, they are staying functional longer, and their quality of life has improved. Unlike the older medicines, where if you have some erosions or damage already occurring, they may slow it down but not stop it, these medications can actually stop the damage and destruction in the joints.

What biologics are being studied to treat RA in the future? How are these different from current biologics?** Dr. Jerome:** There are other biologic medications that are being studied for the treatment of RA. As good as the current collection of biologic medications is, there is always value in having more options. There are a few medications that inhibit small molecules, such as proteins called kineases (JAK and Syk), that are being studied. The main difference is that they inhibit the immune system at a different location. These molecules are smaller and may therefore be available as an oral (pill form) medication.

Dr. Morris: We know that there are a number of other pathways that may be a big part of rheumatoid arthritis. We know that there are patients that no matter what we try, it just doesn’t work they just don’t work. In those patients, we’re looking at other pathways that might be involved in RA. We know there are a number of other activating molecules and chemicals that may be ways to go at it. We’re always trying to find medications that may be more specific toward inflammatory pathways and that also won’t have the side effects.