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How Do Biologics Treat Rheumatoid Arthritis?

Posted on December 31, 2020

Article written by Emily Wagner, M.S.

  • Biologics are a category of medications that treat rheumatoid arthritis by targeting specific proteins involved in inflammation.
  • There are several classes of biologics for rheumatoid arthritis that work in different ways.
  • Biologics often work quickly to improve rheumatoid arthritis symptoms and can slow the progress of irreversible joint damage.

Rheumatoid arthritis (RA) is a chronic inflammatory condition where the immune system attacks the lining of joints. While there currently is no cure for RA, many classes of drugs have been developed to help manage symptoms and flares. Biologic drugs work to lower inflammation by interacting with immune cells or other inflammatory mediators to slow joint damage associated with RA.

What Are Biologics?

Biologics are drugs made of proteins, sugars, or nucleic acids. Unlike other drugs that are chemically synthesized, biologics are derived from living organisms. Examples of biologics include vaccines, gene therapy, and monoclonal antibodies used to treat cancer and RA. Biologics that are disease-modifying antirheumatic drugs (DMARDs) can be used to treat rheumatic diseases, including RA.

All biologics are given as injections — either subcutaneous (under the skin) or intramuscular (into muscle) — or as IV infusions. Biologics cannot be taken by mouth because they would be broken down in the stomach and intestines before being absorbed into the bloodstream.

Biologics can be used on their own or in combination with other DMARDs like Methotrexate or Janus kinase (JAK) inhibitors (such as Xeljanz, Olumiant, or Rinvoq) to treat RA.

To understand how biologic DMARDs are used to treat RA, it is important to know a little more about the immune system, inflammation, and a class of biologics known as monoclonal antibodies.

What Are Monoclonal Antibodies?

Antibodies are an important component of the body’s immune system. They are usually made by specialized immune cells, known as B cells, when there is a bacterial or viral infection. The human body is capable of making almost 100 billion different types of B cells, and each type of B cell produces only one type of antibody. Each antibody is a protein that recognizes and interacts with a very specific target.

B cells can also be genetically altered in a lab to produce specific antibodies that will attach to a target protein. These are known as monoclonal antibodies because they are produced from one type of B cell.

Every antibody made by that B cell will have the same properties. Researchers have designed monoclonal antibodies to target specific proteins on the outside of immune cells, cancer cells, and more.

Classes of Biologics for Rheumatoid Arthritis

There are four main classes of biologics used to treat RA, including B-cell inhibitors, tumor necrosis factor alpha (TNF-ɑ) inhibitors, selective costimulation modulators, and interleukin inhibitors. Each class of biologics interferes with different aspects of the immune system involved in inflammation and joint damage in RA.

B-Cell Inhibitors

B cells are an important part of an immune system response. These cells are responsible for making antibodies that are used to fight off infections and build immunity. In the case of autoimmune diseases, B cells make autoantibodies that attack the body’s own healthy tissues. This eventually leads to joint damage and inflammation.

In RA, autoantibodies attack the lining of joints, known as the synovium. B cells can also release tumor necrosis factor alpha, a cytokine (signaling protein) which is responsible for causing damage in RA.

B-cell inhibitors are biologics used to kill B cells in the blood, stopping them from making autoantibodies and TNF-ɑ. This helps prevent the immune system from attacking the synovium in joints and lowers inflammation.

The U.S. Food and Drug Administration (FDA) has approved Rituxan (Rituximab) to treat RA in cases when other treatments have not worked. Rituxan was originally approved for treating B-cell lymphoma, but it is also effective in treating RA.

Tumor Necrosis Factor Alpha Inhibitors

Tumor necrosis factor alpha is an inflammatory cytokine responsible for causing inflammation and bone degradation in RA. TNF-ɑ can be found in high levels in the joints of people with RA, where it binds to receptors on the outside of cells. Monoclonal antibodies have been developed to block TNF-ɑ. These biologics work in a few different ways.

The first is by blocking TNF-ɑ access to its receptors on a cell. If TNF-ɑ cannot bind to its receptors, then it cannot turn on an inflammatory response. Drugs that block receptors from other proteins are called antagonists. One example of a TNF-ɑ antagonist is Humira (Adalimumab).

The second way a biologic can inhibit TNF-ɑ is by binding directly to the protein and neutralizing (destroying) it, so it cannot bind to its receptor. Examples of TNF-ɑ-neutralizing antibodies include Remicade (Infliximab), Simponi (Golimumab), and Cimzia (Certolizumab pegol).

The third and final way TNF-ɑ inhibitors work is by mimicking the TNF receptor. Enbrel (Etanercept) is a genetically engineered protein that is the same shape as the TNF receptor. When injected, Enbrel “soaks up” free TNF-ɑ in the joints so it cannot bind to its receptors.

Selective Costimulation Modulators

Selective costimulation modulators are biologics that work by blocking the function of a group of immune cells known as antigen-presenting cells (APCs). APCs activate other immune cells, like T cells, by binding to special receptors called costimulation receptors. Once turned on, the T cells will then increase inflammation. In the case of RA and other autoimmune diseases, APCs may activate autoreactive T cells, which attack the body’s own tissues.

Orencia (Abatacept) is a biologic that works by binding to the costimulatory receptors on APCs. This blocks T cells and APCs from interacting with one another and shuts down any immune response between the two cells.

Interleukin Inhibitors

Interleukins (ILs) are a group of cytokines that help turn on various immune cells. They bind to receptors on the outside of cells to trigger inflammatory signaling pathways. Specifically, IL-1 and IL-6 contribute to inflammation in RA.

Interleukin inhibitors are biologics created to block these cytokines from creating more inflammation. Kineret (Anakinra) is an IL-1 receptor antagonist that works by blocking IL-1 binding to cells. Actemra (Tocilizumab) works similarly, blocking IL-6 binding to cells.

How Effective Are Biologics for RA?

Biologic DMARDs have been shown to slow irreversible joint damage, similarly to other RA drugs like JAK inhibitors. In studies, biologics begin working quickly and often relieve symptoms of RA within a few weeks. TNF-ɑ inhibitors may begin working as early as a few days after the first dose.

In clinical trials studying RA, drugs are rated using the ACR20, ACR50, ACR70 scale. This scale was developed by the American College of Rheumatology, and measures a 20 percent, 50 percent, or 70 percent improvement in RA symptoms. In multiple trials, biologic DMARDs worked better than other drugs, such as Methotrexate alone. Participants who were treated with biologics saw more improvement in their ACR20, ACR50, ACR70 scores than those who did not receive biologics.

Unfortunately, there is currently no cure available for RA. The overall goal of treatment is to stop or reduce inflammation to the lowest levels possible in order to relieve symptoms and slow further joint damage.

If RA continues to progress, it can lead to permanent joint damage and disability. DMARDs, like biologics, can control active rheumatoid arthritis and reduce inflammation, helping you lead a healthier life.

Read about how RA treatments slow the progress of irreversible joint damage in rheumatoid arthritis.

Read about how JAK inhibitors work to treat rheumatoid arthritis.

Finding Support for Rheumatoid Arthritis

You are not alone in living with RA. When you join myRAteam, you gain a community of more than 137,000 people who know what it’s like to live with rheumatic disease.

Here are a few recent myRAteam conversations about biologics as a treatment option:

Have you used biologics to manage your RA? What was your experience? Share in the comments below or start a conversation on myRAteam.

References

  1. What Are “Biologics” Questions and Answers — Food and Drug Administration
  2. Non-invasive delivery strategies for biologics — Nature Reviews Drug Discovery
  3. Understanding Methotrexate — Arthritis Foundation
  4. The Use of Biologics in Rheumatoid Arthritis: Current and Emerging Paradigms of Care — Clinical Therapeutics
  5. Antibody — National Human Genome Research Institute
  6. Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire — Proceedings of the National Academy of Sciences
  7. Developments in therapy with monoclonal antibodies and related proteins — Clinical Medicine Journal
  8. Biologics — Arthritis Foundation
  9. B Cells and Antibodies — Molecular Biology of the Cell. 4th edition.
  10. B-cell inhibitors as therapy for rheumatoid arthritis: an update — Current Rheumatology Reports
  11. Efficacy and Safety of Belimumab in Patients with Rheumatoid Arthritis — The Journal of Rheumatology
  12. Rituximab for the treatment of rheumatoid arthritis: an update — Drug Design, Development and Therapy
  13. Impact of Rituximab (Rituxan) on the Treatment of B-Cell Non-Hodgkin’s Lymphoma — Pharmacy and Therapeutics
  14. The role of TNF-ɑ in rheumatoid arthritis: a focus on regulatory T cells — Journal of Clinical and Translational Research
  15. Localization of tumor necrosis factor ɑlpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis — Arthritis & Rheumatism
  16. TNF inhibitor therapy for rheumatoid arthritis — Biomedical Reports
  17. Adalimumab in the treatment of arthritis — Therapeutics and Clinical Risk Management
  18. Infliximab in the treatment of rheumatoid arthritis — Biologics: Targets and Therapy
  19. Golimumab for Rheumatoid Arthritis — Journal of Clinical Medicine
  20. Certolizumab pegol in the treatment of rheumatoid arthritis: a comprehensive review of its clinical efficacy and safety — Rheumatology (Oxford)
  21. Etanercept in the treatment of rheumatoid arthritis — Therapeutics and Clinical Risk Management
  22. Selective Costimulation Modulators: Addressing Unmet Needs in Rheumatoid Arthritis Management — Medscape General Medicine
  23. Abatacept: A Review in Rheumatoid Arthritis — Drugs
  24. Interleukin — StatPearls
  25. Cytokines in the Pathogenesis of Rheumatoid Arthritis and Collagen-Induced Arthritis — Madame Curie Bioscience Database [Internet]
  26. The Role of Interleukin 6 in the Pathophysiology of Rheumatoid Arthritis — Therapeutic Advances in Musculoskeletal Disease
  27. Blocking Interleukin-1 in Rheumatic Diseases — Annals of the New York Academy of Sciences
  28. Interleukin-6 inhibitors in the treatment of rheumatoid arthritis — Therapeutics and Clinical Risk Management
  29. Rheumatoid arthritis response criteria and patient-reported improvement in arthritis activity — Arthritis & Rheumatology

Emily is passionate about immunology, cancer biology, and molecular biology, and understanding how they relate to diseases. Learn more about her here.

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