What are biologic drugs?

Biologics are called immunomodulatory drugs as they act by modulating the immune system. They are a newer type of injectable drugs and are manufactured proteins.

They act by focusing on the specific function of the immune system, which leads to autoimmune diseases such as psoriasis and rheumatoid arthritis.

A biological drug is made from a living organism (human, animal, or microorganism) or its products with the help of biology.

Biologic products may contain proteins, genes, or altered human hormones, which can act on the human immune system and can either suppress or activate it. They can also change the natural biological intracellular and cellular actions.

Biologic drugs act quickly and bring on periods of remission that make the symptoms go away. Doctors may prescribe biologics on a long-term basis to maintain periods of remission,

The disadvantages of biologics include the heavy expense that can run into several thousands of dollars a year and the limited availability.

Uses of Biologics

Biologic drugs belong to the most advanced medical therapy and are effectively used to treat a variety of conditions.

They have revolutionized the treatment of malignant conditions, reversed the symptoms of autoimmune diseases such as psoriasis and rheumatoid arthritis.

Besides, they have given hope to people with rare diseases. The FDA of the United States has approved biologics for the treatment of more than 800 rare diseases.

Medical uses of biologic drugs include:

  • Various types of cancers. Biologic therapies use your body’s immune system to treat cancer with immunotherapy or to lessen treatment side effects.
  • Rheumatoid arthritis (RA). Biologic drugs are a newer form of treatment for rheumatoid arthritis. They are usually advised in combination with methotrexate or another disease-modifying antirheumatic drug (DMARD) when DMARDs have not been effective on their own.
  • Psoriasis. Biologic drugs have proved to be quite effective in the treatment of moderate to severe psoriasis, which has not responded to traditional therapy.
  • Psoriatic arthritis. They are also useful in treating psoriatic arthritis. Being relatively new, their long-term effects are still to be ascertained.
  • Crohn’s disease and ulcerative colitis. Biologics are prescribed to people with moderate to severe Crohn’s or Colitis when other treatments have failed to give the desired results. Gut inflammation flare-ups in Crohn’s and Colitis are caused by the immune system going into overdrive. Biologic drugs act to block the overactivity of the immune system, which reduces inflammation and improves symptoms. In other words, biologics target and suppress the inflammation response that can trigger the flares in these conditions.
  • Ankylosing spondylitis. Biologics are useful for improving the back pain and stiffness of ankylosing spondylitis by reducing inflammation, improving physical activity, and reducing fatigue.
  • Multiple sclerosis (MS). In MS, biologics reduce chronic brain inflammation that damages the myelin or protective membrane around the nerves. They have proven effective at improving the quality of life of many patients.
  • Systemic lupus erythematosus (SLE). In SLE, biologics may enhance therapeutic efficacy when combined with standard therapies.
  • Diabetic retinopathy. The main biologics used in diabetic retinopathy are called ranibizumab (Lucentis) and aflibercept (Eylea). They stop the condition in your eyes from getting worse, and may also improve your vision.
  • Osteoporosis. The United States Food and Drug Administration approved Denosumab (Prolia), a biologic drug, for the treatment of postmenopausal osteoporosis in the year 2010. Patients experienced a significant increase in bone mineral density and a reduced risk for new vertebral fractures
  • Bronchial asthma. By targeting antibodies, inflammatory molecules, or cell receptors, biologics disrupt the pathways that lead to inflammation and are responsible for asthma symptoms.
  • Human immunodeficiency virus (HIV). Though the evidence is limited, biologic agents may have a favorable effect on CD4 and HIV viral counts when used with accompanying HAART (Highly Active Antiretroviral Therapy).

Different types of biologic drugs

Various types of biological drugs and their therapies include:

  • Blood or its products such as platelets
  • Steroid hormone therapies help control metabolism, inflammation, and immune functions, regulate salt and water balance, and develop sexual characteristics.
  • Vaccines are given to prevent infectious diseases. Each disease has a specific vaccine.
  • Antitoxins: An antitoxin is a specific antibody manufactured to neutralize a specific toxin (such as to treat a snakebite)
  • Recombinant proteins are a novel grouping of genes that forms DNA. (examples include insulin or erythropoietin)
  • Interleukins are a subset of cytokines, which are modulators of cell behavior and used to treat certain infections and cancers)
  • Tendons, ligaments, or other materials used for transplantation
  • Monoclonal antibodies (like those used to treat autoimmune diseases and cancer)
  • Stem cell therapies are used to transplant blood stem cells to treat diseases and conditions of the blood and immune system (such as for certain cancers or genetic diseases)
  • Gene therapy replaces a faulty gene or adds a new gene to treat a wide variety of diseases, such as cancer, heart disease, diabetes, hemophilia, and AIDS.

Mechanism of action

Traditional systemic drugs influence the entire immune system. Biologics impact specific parts of the immune system.

In psoriasis disease, they target a specific type of immune cell called a T-cell and block its action. They also block the proteins of the immune system namely tumor necrosis factor-alpha (TNF-alpha), interleukin 17-A, or interleukins 12 and 23.

These are the cells and proteins that play an important role in developing psoriasis and psoriatic arthritis (PsA) symptoms.

Biologic drugs examples

The following are some examples of biological drugs and their mechanism of action.

1. Alefacept (Amevive, Orencia)

Alefacept is indicated for the treatment of moderate to severe chronic plaque psoriasis by the intramuscular route.

Mechanism of action. Alefacept acts in two ways:

  1. Firstly, it blocks the leukocyte-function-associated antigen (LFA)-3 from interacting with CD2. This inhibits cytokine secretion and the activation and multiplication of the T lymphocyte cells.
  2. Secondly, alefacept induces programmed cell death (apoptosis) of activated memory T cells.

This drug, therefore, acts by decreasing the increased number of activated T cells, which is the main cause of psoriasis symptoms. This drug falls in the category of biologics called T-cell blockers.

2. Etanercept (Enbrel)

This medication is used alone or in combination with an immunosuppressant (such as methotrexate) to treat certain types of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and skin psoriasis.

Mechanism of action

TNF (Tumor necrosis factor) is a naturally occurring cytokine that is responsible for the inflammatory and immune response, which results in the joint pathology seen in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Etanercept inhibits the binding of TNF to cell surface TNF receptors, rendering TNF biologically inactive.

3. Infliximab (Remicade)

Infliximab is used to treat rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and severe skin psoriasis (chronic plaque psoriasis).

Mode of action

Infliximab works by blocking the actions TNF (tumor necrosis factor-alpha), which helps to decrease inflammation and slow down the response of the immune system. This slows or stops the damage from the disease and brings about an improvement in the symptoms.

4. Efalizumab (Raptiva)

Efalizumab was used in the treatment of moderate to severe plaque psoriasis.

Mode of action

This drug acts by blocking the activation of T cells and their migration to the skin. It has however been withdrawn by the manufacturer in 2009.

The company withdrew this drug because of the potential risk of developing progressive multifocal leukoencephalopathy (PML), a progressive neurologic disease caused by a virus that affects the central nervous system.

How are biologics used?

Biologics are administered by injection either by intravenous, intramuscular, or subcutaneous routes. Some biologics can be self-taken at home but intramuscular and intravenous injections are administered at the dermatologist’s office.

  • Amevive is administered by an intramuscular injection by a doctor.
  • Certain biological drugs such as Enbrel are injected into the legs, arms, or abdomen. This, the patient or his family member can do at home.
  • Stelera is given through an I.V. drip by the doctor.

Side effects of biologics

Though derived from natural sources, biologics can cause serious side effects due to their immunosuppressant action (suppression of the immune system of the body).

Such side effects due to immunity suppression are:

  • There is a concern for serious infections and malignancies with these drugs.
  • Mild reactions at the injection site – redness and tenderness.
  • Recurrence of tuberculosis in a patient on these drugs and with a history of TB
  • Other respiratory tract infections can set in due to the suppressed immune system.

Some common side effects include:

  • headache
  • fever with or without chills
  • hives or rash
  • stomach pain
  • back pain
  • nausea
  • cough or sore throat
  • difficulty in breathing
  • fall in blood pressure

Serious side effects that may occur include:

  • certain blood disorders resulting in bruising and bleeding
  • neurological symptoms such as numbness, weakness, tingling,
  • visual disturbances, such as blurred vision, double vision, or even partial blindness
  • lymphoma
  • liver toxicity
  • anaphylactic allergic reactions

Precautions and contraindications for biologics

The following are conditions in which biologic drugs should not be used.

  • Hypersensitivity
  • A compromised immune system
  • Presence of an active infection in the body
  • Biologics are not to be used in cancer patients or in persons with a history of cancer.
  • Precaution should be exercised in patients with infection of hepatitis B or C, tuberculosis, and HIV.
  • A patient who is to start on this therapy must undergo screening tests for the above infections.
  • It is suspected that there may be an increased association of lymphomas in patients on biologics.