In the last decade, there have been significant advances in treating rheumatoid arthritis, especially for patients whose arthritis does not respond to traditional disease-modifying antirheumatic drugs (DMARDs). The most important advance has been the development of a group of drugs called biologic response modifiers or biologics.
There are a number of biologics approved to treat rheumatoid arthritis. These include:
- Abatacept (Orencia)
- Adalimumab (Humira)
- Adalimumab-atto (Amjevita), a biosimilar to Humira
- Certolizumab pegol (Cimzia)
- Etanercept (Enbrel)
- Etanercept-szzs (Erelzi), a biosimilar to Enbrel
- Golimumab (Simponi, Simponi Aria)
- Infliximab-dyyb (Inflectra), a biosimilar to Remicade
- Rituximab (Rituxan),
- Tocilizumab (Actemra)
- Tofacitinib (Xeljanz)
Other biologics are being studied to treat rheumatoid arthritis and other conditions.
How Do Biologics Treat Rheumatoid Arthritis?
Biologics are genetically-engineered proteins derived from human genes. They are designed to inhibit specific components of the immune system that play pivotal roles in fueling inflammation, which is a central feature of rheumatoid arthritis.
Biologics are used to treat moderate to severe rheumatoid arthritis that has not responded adequately to other treatments. They differ significantly from traditional drugs used to treat rheumatoid arthritis in that they target specific components of the immune system instead of broadly affecting many areas of the immune system. Biologics may be used alone but are commonly given along with other rheumatoid arthritis medications.
Biologics have been shown to help slow progression of rheumatoid arthritis when all other treatments have failed to do so. Aggressive rheumatoid arthritis treatment is known to help prevent long-term disability from RA.
What Are the Side Effects of Biologics?
The most common side effect seen with biologics is pain and rash at the injection site. This occurs in less than 30% of patients. Since biologics given by infusion (in the vein) have the potential to cause an allergic infusion reaction, patients are monitored during infusions. Symptoms of infusion reactions include flu-like illness, fever, chills, nausea, and headache.
As with any drugs that suppress the immune system, biologic therapy poses some increased to infections and other diseases. People taking biologics should seek immediate medical attention if they develop persistent fever or unexplained symptoms. Vaccinations that prevent infections should be considered prior to taking biologics. While taking biologic medications people should not receive live vaccines.
Biologics may also cause some chronic diseases that are dormant (such as tuberculosis) to flare, and they are not recommended for people with multiple sclerosis and other conditions such as severe congestive heart failure. All patients should be skin tested for tuberculosis prior to starting biologics, and many are also tested for chronic hepatitis.
Biologics are also more expensive than traditional treatments. However, the evidence so far suggests that they are more effective and may pose fewer risks than other systemic therapies.
One disadvantage to biologic medications is that they must be given either by injection or by intravenous infusion, with the exception of Xeljanz. It is taken by mouth.
Although animal studies of biologics have shown no effect on fertility or impairment of the fetus, these studies cannot always predict the effects in humans. Pregnant women should receive these drugs only if clearly needed, because the effects on a developing child are unknown.
Biologics are commonly discontinued prior to surgery until wounds have healed and infection risk has passed.
As a general rule, different biologic therapies should not be taken at the same time.
Here are some details on available biologic drugs:
Actemra, given by monthly hour-long infusions or weekly (or every other week) injections, is the first IL-6 inhibitor for rheumatoid arthritis. IL-6, or interleukin-6, is a chemical messenger of the immune system.
Actemra is used to treat moderate to severe rheumatoid arthritis in patients who have not responded to one or more TNF inhibitors. TNF inhibitors include Cimzia, Enbrel, Humira, Remicade, Simponi and Simponi Aria.
Adalimumab-atto (Amjevita) is a biosimilar to Humira. It helps reduce the signs and symptoms of rheumatoid arthritis, prevent damage to the body, and improve physical mobility. It can be used alone or in combination with methotrexate.
The most common side effects are infections such as tuberculosis and fungal infections, and reactions at the injection site. More serious side effects include bacterial sepsis and malignancies such as lymphoma.
Cimzia works by blocking the action of a substance in your body called tumor necrosis factor (TNF). Cimzia is an injection. Through the use of prefilled syringes, you can give it to yourself once you are taught to do so by a doctor or nurse. After the initial doses, Cimzia can be taken every 2 to 4 weeks, depending on the dose your doctor feels is right for you.
In addition to pain at the injection site, the most common side effects seen with Cimzia are upper respiratory infections -- such as a cold -- headache, high blood pressure, inflammation of the nose and throat, and back pain.
Enbrel reduces joint inflammation and damage from rheumatoid arthritis by blocking a chemical activator of inflammation called tumor necrosis factor (TNF).
Enbrel is also an injection. Enbrel is given by self-injection under the skin once or twice a week. Patients can learn to give their own injections or receive them from a family member or caregiver who has had proper instruction. Preloaded syringes are available as self-injectable “click-pens.”
Erelzi reduces joint inflammation and damage from rheumatoid arthritis by blocking a chemical activator of inflammation called tumor necrosis factor (TNF).
Enbrel is also an injection. Enbrel is given by self-injection under the skin once a week. Patients can learn to give their own injections or receive them from a family member or caregiver who has had proper instruction.
Humira reduces joint inflammation and damage from rheumatoid arthritis by blocking a chemical activator of inflammation called tumor necrosis factor (TNF).
Humira is an injection. It is given by self-injection under the skin once every two weeks. Patients can learn to give their own injections or receive them from a family member or caregiver who has had proper instruction. Preloaded syringes are available as self-injectable “click-pens.”
This medicine is a biosimilar to Remicade. You will receive this medicine through an IV infusion given by your health care provider. This process will last at least 2 hours. After the first treatment, you will get other doses at 2 weeks and 6 weeks later. Then you’ll have injections every 8 weeks.
Kineret is a protein that reduces joint inflammation by blocking the action of the chemical messenger interleukin-1. The drug is administered as one injection daily (can be self-injected or given by another individual).
In addition to pain at the injection site, the most common effects with Kineret are upper respiratory infection (including sinus infection), headache, and nausea, and diarrhea.
Orencia is a protein that blocks signals that are needed to activate T-cells of the immune system. Activated T-cells play an important role in the development of rheumatoid arthritis.
Like Enbrel and Humira, Remicade reduces inflammation and damage from rheumatoid arthritis by blocking a chemical activator of inflammation, tumor necrosis factor (TNF).
Remicade is given by intravenous infusion in the doctor's office, an infusion center, or hospital. Each infusion takes about two hours. The intravenous treatments are given three times during the first six weeks of therapy, then every eight weeks thereafter.
The most common side effects of Remicade are upper respiratory infection (including sinus infection), nausea, headache, stomach pain, and diarrhea.
Rituxan is used to treat RA that has not improved with TNF-blockers, such as Enbrel, Humira, or Remicade. Rituxan is an antibody protein that works by targeting and reducing the number of specialized white blood cells, called B cells, in the blood. Rituxan is given as two intravenous infusions -- separated two weeks apart. Repeat courses of Rituxan are considered after four to six months.
Rituxan's most common side effects are fever, chills, nausea, headache, and low levels of white blood cells.
Simponi blocks the effects of TNF that triggers inflammation. Simponi is taken once a month by injection (Simponi) or every other month through an IV (Simponi Aria). After a health care professional shows you how to do a self-injection, you can do it yourself at home with either a prefilled syringe or an autoinjector.
In addition to injection site reaction, the most common side effects include upper respiratory infections, runny nose, abnormal liver tests, and high blood pressure.
With any treatment, it is important to meet with your doctor regularly to monitor your progress and to evaluate side effects. Your doctor may periodically order blood tests or other tests to determine the effectiveness of your treatment and detect internal side effects.
Biologic drugs have affected the treatment of rheumatoid arthritis tremendously. As described above, other biologics are being developed that either provide alternative methods or frequency of administration or different targets of action.