Monoclonal Antibodies for Arthritis and Other Diseases

Monoclonal antibodies are man-made proteins that replicate antibodies normally produced by the immune system. Part of a class of therapeutic drugs known as biologics, monoclonal antibodies are used in immunotherapy to treat autoimmune (AI) diseases like rheumatoid arthritis (RA), as well as certain cancers, viral infections, gastrointestinal diseases, and more.

What Monoclonal Antibodies Do

In a healthy immune system, antibodies are produced by white blood cells in response to foreign materials, such as bacteria. 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.

Monoclonal antibodies are laboratory-produced antibodies designed to locate and bind to certain molecules, rendering them neutral in a similar way.

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

How Monoclonal Antibodies Are Made

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 -momab.
• Chimeric monoclonal antibodies are a combination of part mouse and part human proteins. 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. Monoclonal antibodies are extensively tested to ensure purity before they are ready for patient use.

Use for AI Arthritis and Other AI Diseases

Certain diseases are autoimmune in nature. They cause symptoms because the body mistakenly launches an attack on healthy tissue as if is a harmful invader.

In RA, for example, antibodies attack joint tissue, causing pain, inflammation, and stiffness. Monoclonal antibodies treat RA by targeting specific proteins involved in this destructive inflammatory process.

Several cytokine proteins have been identified as contributing to the inflammatory process involved in arthritic and other autoimmune conditions. Monoclonal antibodies have been developed to target these proteins.

TNF 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 doesn't adequately bring the disease into remission. They are also used to treat some other non-arthritic conditions, including certain gastrointestinal diseases.

TNF inhibitors include:

• Cimzia (certolizumab pegol): Delivered via subcutaneous injection, Cimzia is approved to treat adult RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS), as well as Crohn's disease.
• Humira (adalimumab): Produced entirely from human proteins, Humira is 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 healthcare provider's office or clinic, Remicade is approved for the treatment of RA, PsA, AS, Crohn’s disease, and UC. 
• Simponi (golimumab): Delivered as either a subcutaneous injection or IV infusion administered in your healthcare provider's office or clinic, Simponi is approved to treat RA, PsA, AS, and UC.
• Enbrel (etanercept): This receptor fusion protein inactivates TNF, and it is approved for treating RA, PsA, AS, polyarticular juvenile idiopathic arthritis (JIA), and plaque psoriasis (PsO).

Interleukin Blockers

Interleukins (IL), a type of cytokine, 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 and polymyalgia rheumatica (PMR).

IL-6 receptor antagonists approved for the treatment of RA or patients who did not respond to one or more disease-modifying antirheumatic drugs (DMARDs) or some patients with polymyalgia rheumatica (PMR) include:

• Actemra (tocilizumab): The first monoclonal antibody biologic targeting IL-6 on the market, it is delivered by subcutaneous injection or IV infusion in the healthcare provider's office or clinic. It is also approved for two types of juvenile arthritis: JIA, systemic juvenile idiopathic arthritis, giant cell arteritis, and systemic sclerosis-associated ILD. 
• Kevzara (sarilumab): Approved in 2017 for the treatment of RA, this monoclonal antibody biologic also targets IL-6. It is given as a subcutaneous injection. It is also approved to treat people with PMR who do not respond well to corticosteroid treatment or who cannot tolerate corticosteroid taper.

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 healthcare provider's office or clinic.
• Prolia (denosumab): This drug inhibits bone resorption by binding and inhibiting receptor activator of nuclear factor kappa B ligand (RANKL). Approved for treating osteoporosis and to increase bone mass In people who are at a high risk of bone fracture, Prolia has been shown to slow articular bone loss associated with rheumatoid arthritis, but it is not approved for this use. It is given as a subcutaneous injection.

Use for Non-Autoimmune Diseases

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

Cancer

In cancer treatment, 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.
• Others help turn the immune system against cancer. In other words, the monoclonal antibodies "mark" the cancer cells by attaching to their surface so that the immune system knows to kill them.

Besides Rituxan, some examples of monoclonal antibodies used for cancer include Avastin (bevacizumab), Herceptin (trastuzumab), and Vectibix (panitumumab).

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 antibody drugs approved for the treatment of Ebola virus disease include Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn) and Ebanga (Ansuvimab-zykl).

Several monoclonal antibody drugs received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) to treat or prevent COVID-19. However, most of the EUAs for these drugs were later revoked due to limited effectiveness against the predominant Omicron variant.

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 are similar.

In the case of autoimmune types of arthritis in particular, some of the side effects of monoclonal antibodies can overlap with those you have come to expect of the disease itself. Don't let that prevent you from bringing them to your healthcare provider's attention if you experience them.

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 healthcare provider:

• 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 healthcare provider if you experience any of the following in the days after monoclonal antibody treatment:

• Chills
• Diarrhea
• Fatigue
• Fever
• Muscle aches and pains
• Nausea
• Vomiting

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 healthcare provider know if you experience any of these symptoms in the days following treatment with monoclonal antibodies:

• Fever
• Nausea
• Headache
• Low blood pressure
• Rash
• Rapid heartbeat
• Trouble breathing

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, this can result in dangerously low blood pressure and lead to multiple organ failure and shock.

Other Side Effects and Warnings

Monoclonal antibodies can cause mild to severe allergic reactions and other concerns, including:

• Congestive heart failure
• Heart attack
• High blood pressure
• Inflammatory lung disease
• Mouth and skin sores that can lead to serious infections