Monoclonal Antibodies for Arthritis

In This Article

Monoclonal antibodies are man-made proteins that replicate antibodies normally produced by the immune system. Part of a class of therapeutics knowns as biologics, monoclonal antibodies are used in immunotherapy to treat autoimmune diseases like rheumatoid arthritis (RA), psoriatic arthritis (PA), ankylosing spondylitis, and non-radiographic axial spondyloarthritis.

In a healthy immune system, antibodies are produced by white blood cells in response to a foreign invader. Antibodies fight off infection by attaching to foreign proteins called antigens to destroy or neutralize them. For example, when you are exposed to a virus, your body produces antibodies to help rid your system of the infection.

In autoimmune diseases, the body mistakenly launches an autoimmune attack on healthy tissue. In RA, for example, antibodies attack joint tissue causing pain, inflammation, and stiffness. Monoclonal antibodies treat RA by targeting specific proteins involved in the inflammatory process.

What Are Monoclonal Antibodies?

Monoclonal antibodies are laboratory-produced antibodies that are designed to locate and bind to certain molecules, rendering them neutral.

First developed in the 1970s, dozens of monoclonal antibody therapies are available today. They fall into three main categories:

  • Anti-inflammatory
  • Anti-cancer
  • Anti-viral

To develop an effective antibody treatment, researchers first have to identify the specific antigen causing the problem, then engineer antibodies to target it. Once a successful antibody is determined, researchers then replicate—or clone—the antibodies.

The cell base used for cloning the antibodies can be made from mouse or human proteins or a combination of the two and is denoted by the final letters in the drug's generic name. These include:

  • Murine monoclonal antibodies are made from mouse proteins. Their name ends in -omab.
  • Chimeric monoclonal antibodies are a combination of part mouse and part human. Their name ends in -ximab.
  • Humanized monoclonal antibodies are made from small parts of mouse proteins attached to human proteins. Their name ends in -zumab.
  • Human monoclonal antibodies are fully human proteins. Their name ends in -umab.

Producing these man-made proteins is an intricate process that involves placing cells in large stainless steel vats filled with nutrients to produce the specified protein. It is extensively tested to ensure purity before it is ready for patient use.

Monoclonal Antibodies and Arthritis

Several cytokine proteins have been identified as contributing to the inflammatory process involved in arthritic conditions. Monoclonal antibodies have been developed to target these proteins. Here's a closer look at a few different types.

TFN Inhibitors

The first anti-inflammatory monoclonal antibodies developed to treat certain types of arthritis inhibit tumor necrosis factor (TNF), a protein involved in causing the inflammation and damage of rheumatoid arthritis.

TNF inhibitors are commonly prescribed for people with RA after treatment with methotrexate alone fails to bring the disease into remission. TFN inhibitors include:

  • Cimzia (certolizumab pegol): Delivered through subcutaneous injection, it is approved to treat adult RA, PA, and AS, as well as Crohn's disease.
  • Humira (adalimumab): Produced from fully human proteins and approved to treat RA, PA, AS, juvenile idiopathic arthritis, plaque psoriasis, Crohn's disease, and ulcerative colitis (UC). It is administered by injection.
  • Remicade (infliximab): Administered by intravenous infusion in your doctor's office or clinic, it is approved for the treatment of RA, PA, AS, Crohn’s disease, and ulcerative colitis. 
  • Simponi (golimumab): Delivered as either a subcutaneous injection or IV infusion administered in your doctor's office or clinic. It is approved to treat RA, PA, AS, and UC.

Interleukin Blockers

Interleukins (IL) are a type of cytokine that plays essential roles in the activation and differentiation of immune cells. There are at least 40 variants of interleukins involved in the human immune system.

Overproduction of IL-6 is linked to the development of joint pain and inflammation in rheumatoid arthritis. Monoclonal antibodies known as IL-6 inhibitors are used in the treatment of RA.

Two anti-IL-6 receptor antagonists are approved for the treatment of RA in patients who did not respond to one or more DMARDs:

  • Actemra (tocilizumab): The first monoclonal antibody biologic targeting IL-6 on the market, it is delivered by subcutaneous injection or IV infusion in the doctor's office or clinic. It is also approved for two types of juvenile arthritis: polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis. 
  • Kevzara (sarilumab): Approved in 2017, this monoclonal antibody biologic that also targets IL-6 is given as a subcutaneous injection.

Other Targets

Monoclonal antibody therapies have been developed that target other proteins involved in the inflammation process. Drugs used to treat RA include:

  • Rituxan (rituximab): One of the first monoclonal antibodies on the market, it is used to treat autoimmune conditions including RA and lupus in addition to blood cancers. It targets the CD20 antigen found on B cells. It is delivered by IV injection in your doctor's office or clinic.
  • Prolia (denosumab): It inhibits bone resorption by binding and inhibiting receptor activator of nuclear factor kappa B ligand (RANKL). Initially developed to treat osteoporosis, Prolia has been shown to slow articular bone loss associated with rheumatoid arthritis. It is given as a subcutaneous injection.

Other Uses

In addition to treating inflammatory autoimmune diseases like RA, monoclonal antibodies are used to treat cancer and certain infectious diseases.

Cancer

In cancer treatments, monoclonal antibodies are targeted to attack specific types of cancer cells depending on the type of malignancy. They work in two ways. Some therapeutics kill cancer cells directly, while others help turn the immune system against cancer.

Viral Infections

Monoclonal antibodies can be used as passive immunotherapy. Unlike vaccines that trigger a long-term immune response, monoclonal antibodies treat active viral infections by directly targeting that specific virus. They have been used to treat HIV, ebola, and influenza.

Monoclonal antibodies are also being explored as a treatment for COVID-19. In September 2020, Regeneron Pharmaceuticals' monoclonal antibody cocktail REGN-COV2 entered phase 3 trials testing its efficacy in treating the virus responsible for the global pandemic.

The drug, which contains two different monoclonal antibodies that attack the spiked proteins of the novel coronavirus, was administered to U.S. President Donald J. Trump in early October 2020 prior to FDA approval under a compassionate use exemption.

Side Effects of Monoclonal Antibodies

Monoclonal antibodies can have some serious side effects and risks. Individual side effects can vary from drug to drug, but many share similar side effects and warnings. These include:

Needle Site Reactions

The most common side effect of monoclonal antibody treatment involves irritation or infection at the injection site. If you experience any of these side-effects where you received your injection or infusion, tell your doctor:

  • Itchiness
  • Pain
  • Redness
  • Rash
  • Soreness
  • Swelling

Flu-Like Symptoms

Monoclonal antibodies are intended to trigger the immune system and, in doing so, the body may respond with flu-like symptoms. Talk to your doctor if you experience any of the following in the days after monoclonal antibody treatment:

Cytokine Release Syndrome

Cytokines are immune substances with a wide array of functions in the body. A sudden increase in their levels following monoclonal antibody treatment can cause troubling side effects. Let your doctor know if you experience any of these symptoms in the days following treatment with monoclonal antibodies:

Capillary Leak Syndrome

Some monoclonal antibodies can cause fluid and proteins to leak out of tiny blood vessels and flow into surrounding tissues, Known as capillary leak syndrome, it can result in dangerously low blood pressure and lead to multiple organ failure and shock.

Other Side Effects and Warning

Monoclonal antibodies can cause mild to severe allergic reactions and other side effects. These can include:

When to Call 9-1-1

Monoclonal antibody therapy can cause a life-threatening allergic reaction known as anaphylaxis. If you suspect you or someone you are with is experiencing an anaphylactic reaction, seek immediate medical help. Symptoms of anaphylaxis include:

  • Dizziness or fainting
  • Itching, hives, redness, or swelling of the skin
  • Mouth itching or swelling of the lips or tongue
  • Tight or itchy throat, trouble swallowing, or swelling of the back of the throat
  • Shortness of breath, coughing, wheezing, chest pain or tightness
  • Sneezing, stuffy nose, runny nose
  • Vomiting, diarrhea, or stomach cramps
  • Weak pulse
Was this page helpful?
Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. NIH: National Cancer Institute. Monoclonal antibodies. Updated September 24, 2019.

  2. American Cancer Society. Monoclonal antibodies and their side effects. Updated December 27, 2019.

  3. Mallbris L, Davies J, Glasebrook A, Tang Y, Glaesner W, Nickoloff BJ. Molecular Insights into Fully Human and Humanized Monoclonal Antibodies: What are the Differences and Should Dermatologists Care? J Clin Aesthet Dermatol. 2016;9(7):13–5.

  4. Tanaka T, Hishitani Y, Ogata A. Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of tocilizumab with tumor necrosis factor inhibitors. Biologics. 2014;8:141-53. doi:10.2147/BTT.S37509

  5. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26. doi:10.1002/art.39480

  6. American Academy of Rheumatology. Certolizumab Pegol (Cimzia). Updated February 2020.

  7. U.S. National Library of Medicine: Medline Plus. Adalimumab injection. Updated September 28, 2020.

  8. American College of Rheumatology. Infliximab (Remicade). Update February 2020.

  9. U.S. National Library of Medicine: MedlinePlus. Golimumab injection. Updated September 28, 2020.

  10. Justiz Vaillant AA, Qurie A. Interleukin. StatPearls [Internet]. Updated 2020 Aug 30.

  11. American College of Rheumatology. Tocilizumab (Actemra). Updated March 2019.

  12. American College of Rheumatology. Sarilumab (Kevzara). Updated March 2019.

  13. American College of Rheumatology. Rituximab (Rituxan and MabThera). Updated March 2019.

  14. Chiu YG, Ritchlin CT. Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis. Expert Opin Biol Ther. 2017;17(1):119-128. doi:10.1080/14712598.2017.1263614

  15. American College of Rheumatology. Denosumab (Prolia). Updated June 2018.

  16. Pelegrin M, Naranjo-Gomez M, Piechaczyk M. Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing Agents? Trends Microbiol. 2015;23(10):653-665. doi:10.1016/j.tim.2015.07.005

  17. AminJafari A, Ghasemi S. The possible of immunotherapy for COVID-19: A systematic review. Int Immunopharmacol. 2020;83:106455. doi: 10.1016/j.intimp.2020.106455

  18. Regeneron. Recovery COVID-19 phase 3 trial to evaluate Regeneron's REGN-COV2 investigational antibody cocktail in the UK. Updated September 14, 2020.

  19. Davey M, Sample I. Donald Trump receiving Covid-19 treatment yet to be peer-reviewed. The Guardian. Updated October 2, 2020.

  20. U.S. National Library of Medicine: MedlinePlus. Anaphylaxis. Updated September 28, 2020.