Biologic Agents and the Treatment of Autoimmune Disorders

Recombinant DNA Technology

Many biologic agents are created using recombinant (r) DNA technology. rDNA technology starts with DNA, which houses all the genetic information that is needed to create a life. It is made up of two information-rich strands that coil around each other, creating its familiar double helix shape. rDNA is a DNA molecule that is produced in a laboratory by combining one strand of one DNA with another strand from a different DNA, thereby creating a new strand of DNA. In medicine, rDNA can be used to develop drugs or vaccines and to reproduce important human hormones and proteins.

Biologic Agents and the Treatment of Autoimmune Disorders

In autoimmune disorders, the immune system is overactive and destroys not only foreign substances, but also the body’s own tissues. The goal of biologic therapy is to slow or block specific components of the immune system and halt tissue destruction.

Autoimmune disorders treated with biologic agents include:

• Psoriasis: a chronic skin disorder that not only causes skin lesions, but also problems with the joints, fingernails and toenails, genitals, and inside of the mouth. In psoriasis, certain immune cells become overactive, which results in psoriatic lesions developing on the skin and arthritis symptoms developing in the joints. A review published in the Journal of the American Academy of Dermatology looked at the biologic agent infliximab (Remicade) and found that infliximab therapy was helpful in patients with severe psoriasis. In addition, a new biologic agent called ustekinumab (Stelara) was recently approved by the FDA to treat moderate to severe psoriasis.
• Rheumatoid arthritis (RA): a chronic inflammation of the lining of the joints that results in pain, stiffness, swelling, damage, and loss of function. In RA, the immune system initiates chronic inflammation of the lining of the joints.
• Multiple sclerosis (MS): a chronic debilitating disease in which patches of white matter in the central nervous system become inflamed and destroy the insulation (myelin) of the nerve fibers in the brain and spinal cord. In MS, antibodies and white blood cells are responsible for the attack on the myelin sheath that surrounds nerves in the brain and spinal cord, causing inflammation and injury to the sheath and the nerves. A study published in European Neurology studied efficacy, safety, and tolerance of IFN-beta and azathioprine (Imuran; an immunosuppressive agent) combined in patients with relapsing-remitting MS. This study was not a randomized controlled trial, and instead followed patients over time. The researchers found that patients had fewer relapses during the combined treatment period than they did before combined therapy, leading researchers to recommend the drug combination.

Side Effects of Biologic Agents

Because biological agents are very specific in their targets and more precise and predictable, they tend to produce fewer side effects and undesirable consequences than traditional medicines, which are manufactured through synthetic chemical means.

Side effects depend on many factors such as the type of biologic, dosage, route of administration, schedule, and how your body reacts to the biologic agents. Some of the most common side effects of biologic therapies are:

• Flu-like symptoms (fever, chills, muscle and joint aches)
• Loss of appetite
• Nausea and/or vomiting
• Fatigue
• Redness, rash, and/or pain at injection site
• Headache
• Possible allergic reaction to mouse protein with monoclonal antibodies
• Possible reactivation of latent tuberculosis infections with TNF inhibitors (suppress a particular type of immune cell, thereby blocking the inflammation process)
  • Persons who begin treatment with anti-TNF agents should be tested for tuberculosis and treated with anti-tuberculous therapy if found to have latent infection (usually defined as a “positive” tuberculosis skin test).
  • Possibly lymphoma
  • Lupus-like syndrome

A Step Forward in Medicine

Biologic agents are a clear advancement in drug therapy. These newer agents have mechanisms of action targeted toward specific components of the immune system, which enables biologic agents to provide more reliable outcomes with fewer limiting side effects than the more traditional drugs. Many biologic agents have been approved by the FDA (see the following table), and many more are under development.

  * In April 2009, the manufacturer of efalizamab (Raptiva) voluntarily decided to remove it from the market. The medication has been linked to a rare brain infection that can be life-threatening. If you are currently taking Raptiva, talk to your doctor about other treatments.