Getting Started: What to Know About Biologics for Rheumatoid Arthritis

Biologic drugs are genetically engineered proteins that target the parts of the immune system that promote inflammatory processes. They act like natural proteins in your immune system and are considered aggressive treatments for rheumatoid arthritis (RA).

They are often prescribed to people with moderate to severe RA who have not improved using traditional disease-modifying antirheumatic drugs (DMARDs). Biologics are either taken alone or with other RA medications.

In this article, we will discuss what RA is, available biologic treatments for RA, what to expect from these drugs, how to get started, and other considerations, like when you can expect to see improvement, costs, and more.

Rheumatoid Arthritis Basics

RA is a chronic, progressive, and disabling type of inflammatory arthritis. It causes inflammation in and around the joints.

RA is the most common autoimmune disease. The American College of Rheumatology estimates that RA affects up to 1.3 million Americans. It is the result of a person’s immune system mistaking healthy tissues for harmful ones. RA is also a systemic disease, meaning it affects the entire body. 

RA typically affects the hands and feet first. It tends to be symmetrical, affecting the same joints on both sides of the body. Severe RA can affect the organs, including the skin, heart, and lungs.

Additional symptoms of RA include:

• Joint stiffness, especially in the morning and after sitting for long periods
• Fatigue
• A general unwell feeling
• Fever
• Loss of appetite

Treatment for RA aims to:

• Prevent or reduce the severity of flare-ups (periods of high disease activity)
• Relieve pain
• Reduce inflammation
• Slow down or prevent joint damage
• Reduce the potential for disability

The earliest therapies for RA are nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and standard DMARDs. NSAIDs, like ibuprofen and naproxen, reduce pain and inflammation. Corticosteroids can reduce pain and inflammation associated with short-term flare-ups. 

DMARDs calm down the immune system and keep RA from getting worse. One of the first DMARDs prescribed for treating RA is methotrexate. If methotrexate doesn’t calm the inflammation, your doctor may add a biologic DMARD to help manage RA.

Types of Biologics for Treating RA

Biologics are a newer type of DMARD and have greatly improved treatment outcomes for people with RA. They work by blocking the activity of key proteins involved in inflammation. Biologics target specific parts of the immune system.

While biologics are not a cure for RA, they can slow down the disease’s progression. Biologics also cause fewer side effects than other RA therapies. 

Your doctor might prescribe a biologic with or in place of methotrexate or another antirheumatic. Taking a biologic with methotrexate is helpful and effective for many people with RA.

There are different types of biologics used in the treatment of rheumatoid arthritis. Your rheumatologist is in the best position to advise you on whether you might benefit from biologic treatment and which biologic might best help. In general, these drugs are prescribed to people with moderate to severe RA.

They are also prescribed for people for whom other treatments haven’t worked or who can’t take other treatments because of side effects or some other reason.

The types of biologics prescribed to people with RA include B-cell inhibitors, TNF inhibitors, interleukin inhibitors, and T-cell inhibitors.

B-Cell Inhibitors

B-cell inhibitors work by targeting B-lymphocytes (a type of white blood cell) responsible for inflammation. Rituxan (rituximab) is an example of a B-cell inhibitor. 

Risks associated with B-cell inhibitors include blood pressure changes, chest pain, breathing troubles, rash, dizziness, and flu-like symptoms. Your doctor can prescribe medicines that can help reduce some of these effects. Screening for hepatitis and tuberculosis is needed before treatment starts.

Tumor Necrosis Factor (TNF) Inhibitors

TNF inhibitor drugs reduce RA inflammation and slow down the disease’s progression. You might notice improvement after a few doses. Examples of TNF inhibitors include Humira (adalimumab), Cimzia (certolizumab pegol), and Remicade (infliximab).

The anti-inflammatory effects of TNF inhibitors can diminish over time because people can develop antibodies against an anti-TNF drug. The risk of infections, especially fungal infections and tuberculosis (TB), increases with TNF inhibitors. Long-term use might increase the risk of certain cancers.

Interleukin (IL) Inhibitors

IL inhibitors are prescribed to people who don’t get relief from TNF inhibitors. Most are effective and well tolerated by people with RA. Examples of IL inhibitors include Kineret (anakinra), Cosentyx (secukinumab), and Actemra (tocilizumab).

Risks associated with IL inhibitors include infections, including upper respiratory infections and fungal infections. In rare cases, Actemra (tocilizumab) can cause bowel perforation (a small hole in the gastrointestinal tract). Side effects include fatigue, headaches, injection site reactions, abdominal discomfort, and headaches.

T-Cell Inhibitors

Orencia (abatacept) is the first T-cell inhibitor. T-cells are a type of white blood cell involved in inflammation. Orencia works by attaching to the surfaces of these inflammatory cells and blocking communication between them.

By blocking communications, Orencia reduces inflammation. It can also reduce inflammatory symptoms, including swelling, pain, and stiffness. Long-term, Orencia is expected to slow down RA progression and reduce the risk of joint deformity.

The most common side effects of Orencia are headaches, sore throat, and nausea. Serious side effects include infections, such as pneumonia and TB.

Non-Biologic Solutions for RA

RA is also treated with biosimilar drugs and JAK inhibitor drugs. These are newer drug classes that have been approved by the Food and Drug Administration (FDA) over the past decade.

Biosimilars

A biosimilar drug is similar to a biologic. However, it is not an exact copy. Since 2020, the FDA has approved several biosimilar drugs to treat inflammatory arthritis.

You can tell if a drug is a biosimilar if it has a dash after its generic, followed by four letters. For example, the biosimilar to Humira is Hyrimoz (adalimumab-adaz) and the biosimilar to Enbrel is Eticovo (etanercept-ykro).

Biologic drugs tend to be both harder and more expensive to make compared with conventional medicines. It is impossible to make a perfect copy of a biologic because specific cells and different processes are used.

For a biosimilar drug maker to get FDA approval, they must prove that the biosimilar is just as safe and effective as the original and works in the same manner. That means the biosimilar offers the same dosing and the same strength.

However, a biosimilar may not work the same as the biologic, and it is also possible that the biosimilar will cause different or more severe side effects. This is mainly due to your immune response to a particular drug.

JAK Inhibitors

Janus kinase (JAK) inhibitors work by blocking cellular signaling pathways inside cells. This stops processes that promote inflammation. These treatments are available as pills to be taken by mouth.

Xeljanz (tofacitinib) was the first JAK inhibitor approved for treating RA. It was approved by the FDA in 2012. It was followed by Olumiant (baricitinib) in 2018 and Rinvoq (upadacitinib) in 2019.

Research has found an increased risk of heart-related events, like heart attack or stroke, in addition to cancer, death, and blood clots with the use of Xeljanz, Olumiant, and Rinvoq. Because of the risks, these JAK inhibitors are approved for use only when treatment with TNF inhibitors has failed.

So, it's important to work with your doctor to see if these JAK inhibitors are a safe option for you, especially if you are a current or past smoker, or have had heart problems, a stroke, or blood clots in the past.

What to Expect

Most biologics are injected subcutaneously (under the skin). Others must be given by intravenous (IV) infusion (into a vein in your arm).

For injectable biologic drugs, you can usually do this at home on your own or with the help of a loved one. Infusion biologics are done in your doctor’s office, a hospital, or an infusion center.

Injections

Most people who use biologic drug therapies can learn how to use the prefilled syringes or autoinjectors. Your doctor or a member of their staff can show you how to give yourself the injection. If you don’t like giving yourself injections, you can ask a loved one to help you.

Biologic injections should be stored in the refrigerator and warmed to room temperature before being injected. They are given in your thigh or abdomen. You should change the injection site every time you inject yourself so that the same site isn’t used too often.

Dosages for biologic injections will differ based on the drug your doctor has prescribed. Some are given once or twice weekly, others once every other week, and some once a month.

Your doctor or pharmacist can answer any questions you have on your dosing schedule.

Infusions

Biologic infusion treatments for RA include Orencia, Remicade, Rituxan, and Actemra. These medications are given using an IV drip into your vein.

An infusion treatment can take two or more hours to complete. Depending on the drug, your treatments will be done every few weeks.

The infusion starts when the infusion technician inserts a needle attached to a small tube into a vein in your arm. The tube is connected to an IV bag containing the biologic drug. Once the infusion starts, the solution drips into your bloodstream.

Make sure you are feeling well when you arrive for your appointment. Biologic drugs weaken your immune system. If you have an infection starting, the infused drug could make things worse.

After your initial infusion, you will need to be monitored for at least an hour to watch for signs of an allergic reaction. Signs of a drug reaction include shortness of breath, skin rash, and swollen lips.

Headaches are also common after infusions. Fortunately, these headaches usually resolve within a day or two.

You may not see the full effects of an RA biologic until you have been treated for several weeks to several months. Talk to your rheumatologist about how you can manage RA symptoms and flare-ups until your infusion treatment takes effect.

Risks and Side Effects

Much like other therapies, biologic drug therapies come with risks and side effects.

Side Effects

Most people who experience side effects with biologic drug therapy usually experience only mild ones.

Some of the most common side effects linked to biologics are:

• Bruising and injection site reactions (redness, itching, and swelling)
• Headaches
• Fever or chills
• Breathing troubles
• Low blood pressure
• Skin rash or hives
• Stomachache
• Back pain
• Nausea
• Cough
• Sore throat

Potential Risks

Biologic drug therapy is not safe for everyone. You should talk to your doctor if you have had tuberculosis in the past, are prone to infections, or have heart troubles.

Tuberculosis

TB is a serious and infectious lung disease. People who have previously been infected with TB are at an increased risk for reactivation of the infection with biologic drug use.

Your doctor will test you for TB before starting biologic drug therapy. TB infections can be dormant, and it is possible to have been exposed and not know it. If you have had previous exposure, your doctor might recommend TB treatment before starting biologic therapy.

Infections

Biologics can lower your immune system’s ability to fight infections. If you frequently get infections, your doctor might want you on other therapies.

Heart Problems

Some biologics, including anti-TNF inhibitors, can be risky for people with heart troubles.

Tell your doctor if you experience shortness of breath or swelling of the feet while treating RA with a biologic. These might be signs of heart failure—a condition in which the heart cannot pump enough blood to meet the needs of the body.

Other Health Concerns

While rare, biologics can lead to some serious health problems, including:

• Certain blood disorders: Report any usual bleeding or bruising to your doctor.
• Neurological problems: Report numbness, weakness, tingling, or vision changes, such as blurred or double vision.
• Liver damage: Report any yellowing of eyes or skin, severe abdominal pain/swelling, or swelling of the legs.
• Severe allergic reactions: Signs of a severe allergy to a biologic might include shortness of breath, chills, redness, itchy skin, itchy eyes, or itchy lips. If you develop any of these symptoms, seek immediate medical attention.
• Lymphoma: Early signs of lymphoma include enlarged lymph nodes, extreme fatigue, and weight loss. Reach out to your doctor if you are experiencing these symptoms.

Biologic drugs are generally not recommended for anyone who is pregnant or breastfeeding, as these drugs have not been thoroughly studied in these groups. If you are pregnant or breastfeeding, talk to your doctor about other options to treat RA.

Getting Started

Your rheumatologist will want you on DMARDs like methotrexate before starting you on a biologic. Because biologics are expensive drugs, some health insurance companies won’t cover biologics until other RA therapies have failed.

Before starting a biologic drug for RA, your doctor will screen you to confirm whether you’re a candidate for the drug. They will look at your medical history and how biologic therapy might help you to manage RA.

Your doctor will also talk to you about dosages, scheduling, and methods for administering a biologic drug. You may also need to take some vaccinations before starting a biologic to prevent infections since biologics suppress the immune system.

If you are feeling sick, you should hold off on starting a new biologic drug. This is because biologics impair the immune system and increase the risk of infections. If you feel sick—even if it is just a cold—your doctor needs to know.

If you get sick or develop an infection while on a biologic, see your doctor. Your doctor will want to treat you quickly before things get worse.

You will need to be screened for TB and hepatitis B before you start biologic drug therapy. Both are infections that can reactivate with biologic therapy. Your doctor may also screen you routinely for both infections.

People who use biologics shouldn’t have live vaccines because they can cause serious health problems. This includes vaccines for chickenpox, MMR (measles, mumps, and rubella), and pneumonia. After starting therapy, check with your doctor before getting routine vaccines, such as the flu shot.

Other Considerations

Your experience using a biologic drug to treat RA will be different than that of others with RA on the same drug. There are several things to consider as you start therapy and continue treating with a biologic drug.

Timing of Improvement

Make sure you are patient with your new treatment. It will take time for you to notice a difference in how you feel. Most people start to feel better on biologics and have fewer RA symptoms, but it may take up to several weeks before you feel the full effects of a biologic drug.

Cost

Biologic drugs are more expensive than oral DMARDs. They can cost between $10,000 and $30,000 per year for one person.

If your doctor prescribes a biologic to treat your RA, you will still owe a portion of the cost even after insurance. That amount could be hundreds of dollars a month. If you can’t afford that amount, there are still ways you can get the biologic your doctor has prescribed.

• Patient assistance plans: Many drug companies offer programs for people who cannot afford their drugs. These may cover copayment amounts or offer the drug at a discount or no cost. Your doctor’s staff can let you know if a drug company offers assistance, or you can find that information on the drug’s website.
• State programs: If you are older or disabled and don’t have drug coverage, your state may have an assistance program. The Medicare website’s prescription drug assistance tool can help you find resources in your state.
• Private foundations: Organizations like NeedyMeds and RxAssist are additional sources for getting your medicines if you cannot afford them. If you are at risk of going without treatment, let your doctor’s office know. They can offer you information about drug assistance programs.
• Pharmacy discount programs: Some pharmacies have discount programs, so ask yours what it offers. Another option is GoodRx, a telehealth resource that works with pharmacies in the United States to provide drug coupon discounts.

Biosimilar drugs are another option for reducing your drug costs. Check with your doctor about whether a biosimilar drug might be an option for you.

Managing Flares

You might still experience flare-ups even while treating RA with a biologic. Flare-ups can be unpredictable. One day you are feeling fine, and the next you are struggling to care for yourself.

If you are experiencing frequent flares despite being on various treatments for RA, talk to your doctor about whether your current treatment plan is working or whether you need to start on a new biologic to treat RA.

Your treatment plan might not be the reason you are experiencing frequent flares. Much like other types of inflammatory arthritis, RA is linked to triggers—things like diet, stress, smoking, and too much alcohol. Doing what you can to avoid triggers can mean fewer flares and improved quality of life.

Sticking to Your Treatment Plan

A 2018 report in the journal Arthritis & Therapy found that 50% to 70% of people with RA were nonadherent with their recommended treatment plans. Nonadherence to treatment is one of the main reasons RA treatments fail.

Your rheumatologist has prescribed biologic drug therapy because they believe that the benefits outweigh the risks. The good news is that many of the newer biologic drugs are safe and effective.

If you feel you need to stop your biologic drug because of side effects, cost, or another reason, talk to your rheumatologist first. The decision to stop, change, or reduce the dosing of a drug should be made by you and your doctor, and not one you make alone.

Summary

Biologics are powerful drugs that slow down or stop damaging inflammation. They are usually prescribed when conventional DMARDs haven’t helped. Biologics work very well for many people with RA.

They can be expensive drugs because they are harder to make than standard DMARDs. Some come as an injection you can give yourself, while others have to be given at your doctor’s office or an infusion center through IV infusion.

You may get infections more frequently because biologics weaken your immune system. You should let your doctor know if you are prone to infections.

A Word From Verywell

A biologic might work for some people and not for others. And one biologic might work for you early on, and then it may stop working after a while. If a biologic drug doesn't help you or stops working, your rheumatologist can recommend another biologic or RA treatment that might better help.

Many people with RA can achieve low disease activity or remission using biologics. So, until you get there, don’t give up. Keep working with your doctor until you find a biologic that helps you get your RA under control.