An Overview of Biologics for Lupus Treatment

In the past 10 years, a new class of drug called biologics (sometimes called biological medical therapy) has led to new, successful treatments for lupus and other inflammatory diseases. Biologics for lupus include Benlysta (belimumab) as well as many biologics being tested in clinical trials.

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Systemic lupus erythematosus (often referred to as SLE or lupus) is an autoimmune disease that leads to inflammation in the body’s connective tissue. Autoimmune diseases develop when the body’s immune system accidentally starts attacking healthy parts of the body instead of an invader. The joints, skin, blood vessels, and various organs are usually most impacted by lupus.

Additional types of lupus revolve around the various organs that are most impacted, including: 

  • Lupus nephritis is when the immune system’s reaction damages the kidneys, impacting about one-third of lupus patients. 
  • Cutaneous lupus is when the symptoms of lupus manifest mostly in the skin as rashes or sores on the face, ears, neck, arms, and legs. 
  • CNS lupus is when the symptoms of SLE manifest in the central nervous system (CNS)—the brain, spinal cord, and nerves. This can lead to seizures or stroke.

Biologics are being tested for many of these forms of lupus, but the only approved biologic treatment for lupus, Benlysta, is approved only for SLE and lupus nephritis.

This article will define the types of biologics being tested to treat lupus, the specific drugs used for lupus treatment, and the benefits and risks of these types of treatments. 

What Are Biologics?

Biologics are a type of treatment new to the market over the last few decades. These drugs are genetically engineered proteins based on the body’s natural proteins and use live systems to manufacture them. Biologics target specific areas of the immune system that cause inflammation.

Biologics are usually created by cells grown in the lab. They can also be isolated directly from humans or grown in animals. Traditional “small molecule” drugs are created in the lab with chemicals, not using living things to grow them.

Biologics have many names. They may be called “biologic therapy,” “biological therapy,” “biologicals,” or “biopharmaceuticals.” They include a large class of drugs made up of many different types. 

The types of biologics that are approved and being tested for treating lupus fall into three specific categories. 

The largest category is antibody-based therapies. Antibodies are a special type of protein, which are large molecules made up of amino acids. They naturally occur in our bodies, created by the immune system to act as natural defenses against infection.

They have special arms with sections that are custom-made to match up with specific proteins on invaders like viruses and bacteria. When antibodies bind to these invaders, they send signals to the rest of the body to attack the invaders. These custom arms can be made in the lab to attach to and mark many different proteins, not just those from germs.

Three specific technologies are being used to treat lupus:

  • Monoclonal antibodies are traditional whole antibodies, very much like those in our bodies naturally.
  • Antibody fragments are pieces of that whole antibody broken into new components that can give the drug different properties. They usually retain the customized arms but may remove the main body of the antibody proteins or recombine the pieces in a different structure.
  • Bispecific antibody therapies take two different custom arms and combine them into one antibody molecule. 

Most of the antibody therapies being tested for lupus work by turning down the number of B-cells in the body. B-cells are immune cells that make the autoantibodies that cause illness in lupus. Others work by turning down other parts of the immune system involved in lupus.

Two other types of biologics in testing for lupus are:

  • Recombinant proteins are produced by bacteria or cells that have been genetically engineered to create large quantities of that protein.
  • Cell therapies, including stem cells, may be used.

How Biologics Can Be Used to Treat Lupus

So far, the only approved biologic to treat lupus is Benlysta. Benlysta is a monoclonal antibody that inhibits B-cell survival. It is used to treat lupus patients who have autoantibodies (antibodies that attack the body). It was approved by the Food and Drug Administration (FDA) on March 9, 2011.

In lupus and other related conditions, the immune system itself stops working properly. Biologics and other drugs aim to get it working normally again by turning certain cells and proteins of the system up or down. 

Before Benlysta was approved in 2011, there had been a 50-year lull in new treatments for lupus. The only approved drugs for SLE had been Plaquenil (hydroxychloroquine), prednisone (a corticosteroid used to reduce inflammation), and aspirin.

These and other drugs that had been used off-label for lupus are general immune system dampeners. They suppress the entire immune system, not just the parts that act up. 

But biologics like Benlysta are targeted treatments. They can turn down just specific parts of the immune system that lead to inflammation or specific autoimmune responses that lead to other symptoms of lupus. 

Benlysta, specifically, turns down a protein that stimulates B-cells. B-cells are a type of white blood cell that make antibodies. In lupus, these cells attack and damage the body’s healthy tissues instead of hunting down viruses or bacteria.

Off-Label Biologics and Clinical Trials

In "off-label" use, a biologic approved by the FDA for other conditions might be prescribed for lupus, although rheumatologists (doctors who diagnose and treat autoimmune diseases) rarely do so. Patients with various forms of lupus might be enrolled in clinical trials of biologics approved for other conditions or not yet approved for any condition.

Rituxan (rituximab) is a monoclonal antibody approved to treat blood cancers, rheumatoid arthritis, and several other conditions. It is used (rarely) off-label for systemic lupus erythematosus.

It works similarly to Benlysta and is being tested for long-term treatment of systemic lupus to prevent flare-ups, times when disease symptoms are present. Original clinical trials of Rituxan weren’t successful in meeting their goals but did meet secondary goals and seem to show effectiveness in certain subsets of lupus patients.

Anifrolumab is a monoclonal antibody treatment specifically designed for lupus that was recently FDA-approved after completing its phase 3 clinical trials.

Clinical Trials

In clinical trials, treatments are given to patients and the effects and safety of the treatments are studied. Phase 1 trials focus on safety. Phase 2 trials check for effectiveness. Phase 3 trials compare the safety and effectiveness with standard treatments. After these, the drug may be evaluated for FDA approval.

Biologics approved for other conditions that are being studied in clinical trials for patients with various forms of lupus include:

  • Ultomiris (ravulizumab-cwvz) is a monoclonal antibody biologic. It is approved to treat paroxysmal nocturnal hemoglobinuria (a rare, life-threatening blood disease) and atypical hemolytic uremic syndrome (an extremely rare blood disease).
  • Cosentyx (secukinumab) is an FDA-approved monoclonal antibody for the treatment of the autoimmune diseases plaque psoriasis (affects the skin), ankylosing spondylitis (affects the spine), and psoriatic arthritis (affects the joints). It’s currently in phase 2 trials for the treatment of discoid lupus erythematosus, a type of cutaneous lupus, and phase 3 trials for lupus nephritis.
  • Tremfya (guselkumab) is a monoclonal antibody that treats plaque psoriasis and psoriatic arthritis. It’s currently in phase 2 trials for lupus nephritis.
  • Darzalex (daratumumab) is a monoclonal antibody used to treat a cancer called multiple myeloma. It’s being tested against lupus nephritis in phase 2 clinical trials.
  • Itolizumab is a monoclonal antibody in phase 1 trials for lupus nephritis and SLE. It was actually approved for “restricted emergency use” against COVID-19 in 2020 and has been used against plaque psoriasis in India.
  • Narsoplimab (OMS721) is a monoclonal antibody that currently has FDA breakthrough therapy and orphan drug designations for multiple other conditions. It is currently being tested for its effectiveness in treating lupus nephritis.

New biologics for lupus that have not been approved yet but are being tested in clinical trials include:

  • Iscalimab (CFZ533) is a monoclonal antibody being tested against SLE and lupus nephritis that is currently in early-stage clinical trials.
  • Ianalumab (VAY736) is a monoclonal antibody in early trials for the treatment of SLE and lupus nephritis.
  • VIB7734 is a monoclonal antibody. It is currently in phase 2 trials.
  • Efavaleukin alfa (AMG 592) is a biologic created by fusing a protein called interleukin-2 to the unchangeable part of a monoclonal antibody that interacts with the rest of the immune system. It’s being tested for the treatment of inflammation and graft-versus-host disease.
  • Rozibafusp alfa is a bispecific antibody linked to a short protein. It’s being tested for treatment of lupus in phase 2b studies.
  • LY3471851 (NKTR-358) is a recombinant protein version of the immune system protein interleukin-2. It’s in phase 2 clinical trials in lupus.
  • ALPN-101 is an engineered antibody fragment. It is currently in phase 2 trials.
  • Dapirolizumab pegol is an antibody fragment. It is currently in phase 3 studies for SLE.
  • CS20AT04 is a stem cell–based therapy that may reduce the production of autoantibodies through the anti-inflammatory effect and immune function control. It’s being tested for efficacy in SLE in phase 2 clinical trials.
  • BIIB059 is a monoclonal antibody. It is in phase 3 studies for SLE.​​

Benefits and Risks of Biologics for Lupus

When used in addition to traditional lupus therapies, Benlysta has shown to be safe and effective at helping decrease symptoms of lupus without increasing side effects. It can even help lupus patients use fewer steroids like prednisone. These corticosteroids can lead to bone loss and organ damage when used for a long time. 

There are risks from these drugs, specifically side effects, including the potential for an allergic reaction. It’s also possible they just won’t work well for you. Many clinical trials of biologics for lupus have failed to show the desired effects.

Treatment Procedures of Benlysta for Lupus

There are two ways to take Benlysta. You can get it as an infusion through a vein at a clinic, or you can use a self-injecting device to administer the dose at home.

If you get the drug as an intravenous (IV) infusion, you’ll need to go to an infusion clinic, hospital, or doctor’s office. Your healthcare provider will place a needle into a vein in your arm connected to a tube that will drip the medicine slowly for about an hour. 

When you first start Benlysta infusions, you’ll go in every two weeks for the first three infusions. From then on, you’ll only need to go in once every four weeks. 

If you choose to administer your injections at home, you’ll likely need some training from your doctor to ensure you’re doing it right. 

You can choose either prefilled syringes of the drug or an autoinjector, which looks like a pen and automatically injects the medication when pressed against the skin. Your autoinjector prescription will need to be filled by a special pharmacy and kept refrigerated before use.

The injector delivers the antibody drug under the skin while you're at home. Prefilled syringes require you to insert a needle and press down the plunger to administer the medication, but they may be cheaper. 

You’ll need to inject the medicine either into your abdomen or your thighs. Doses should be given once a week, every week. You’ll need a sharps container for safe disposal. 

For many people, self-injecting is easier and more convenient than going to a clinic. Others prefer the IV route if they’re fearful of needles, squeamish about self-injecting, or don’t want to do it every week.

Whichever way you choose to take Benlysta, you may experience side effects. These include:

  • Headache
  • Pain in the arms or legs
  • Trouble sleeping
  • Digestive symptoms (nausea, diarrhea, vomiting, stomach pain)
  • Cold-like symptoms (runny nose, stuffiness, coughing) 

These side effects are typically mild, but it’s possible that you could sustain an allergic reaction that makes it hard to breathe. If that happens, call 911 immediately.

You’ll likely continue with your regular treatments while taking Benlysta. It may take weeks or months for the drug to start working. At that point, you can discuss with your doctor the option of going without some of your other drugs.

Summary

Benlysta is a biologic drug approved for use in lupus. It is given by infusion or injection. Many other biologic drugs approved for other conditions or in development are being studied in clinical trials to see if they are effective and safe for use in lupus.

A Word From Verywell

Lupus can be a difficult disease to manage. Talk to your doctor about the risk and benefits of using biologics to treat your lupus. Many people find relief using Benlysta, though there are side effects. Your doctor may suggest you enroll in a clinical trial of other biologics being developed and tested.

Frequently Asked Questions

  • Can biologics be used as a treatment for lupus erythematosus?

    Many biologics have been developed to treat inflammatory and autoimmune disorders. Only Benlysta is approved for lupus.

  • What are the most common types of biologics for lupus?

    The only approved biologic for lupus, Benlysta, is a monoclonal antibody that inhibits B-cells that produce antibodies that attack the body. Rarely, doctors prescribe Rituxan off-label. It is also a monoclonal antibody.

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