Treatment Options for Scleroderma

Investigational Treatments for Scleroderma

A variety of new treatments are currently being investigated for the treatment of systemic scleroderma in hopes of better controlling symptoms and slowing down the progression of the disease. Examples include:

  • Interferons
  • Tumor necrosis factor alpha blockers
  • Halofuginone
  • Plasmapharesis
  • Photopheresis
  • Autologous stem cell transplantation

Interferons

Interferons are a naturally occurring group of proteins that act as chemical messengers between cells of the immune system. Three types of interferons (alpha, beta, and gamma) have been discovered so far each of which plays an important role in immune-medicated reactions. Currently, interferons are used as immunotherapy for the treatment of some types of cancers and some autoimmune disease.

Recombinant gamma-interferon (e.g., Actimmune) represents a potentially effective therapy for scleroderma because it inhibits excessive production of collagen and may reduce fibrosis of organs in scleroderma. There is some evidence that it may also improve skin softening. In one study, the 5-year survival rate of patients with diffuse scleroderma who were treated with recombinant gamma-interferon was about 85%.

Tumor Necrosis Factor-Alpha Blockers

Drugs that block the action of tumor necrosis factor-alpha (TNF-alpha), a potent immune system mediator of chronic inflammation, are currently being used to treat a variety of chronic inflammatory diseases including Crohn's disease, psoriatic arthritis, and rheumatoid arthritis with good success. Because anti TNF-alpha blocking drugs can reduce or modify the chronic inflammatory response, there is significant interest in evaluating these drugs for the treatment of other chronic inflammatory conditions such as scleroderma. Examples of anti TNF-alpha blockers include:

  • infliximab (Remicade)
  • etanercept (Enbrel)
  • adalimumab (Humira)

Halofuginone

Halofuginone is a drug that specifically inhibits collagen type I synthesis and is, therefore, a potentially effective treatment for systemic scleroderma. In March, 2000 the U.S. Food and Drug Administration (FDA) designated halofuginone as an "orphan drug" - a drug specifically developed to treat a rare disease that affects less than 200,000 people in the United States. Orphan drug designation also provides companies that are developing the drug with financial incentives (e.g., tax breaks) to develop and test the drug and bring it to market. Halofuginone has been shown to reduce collagen synthesis and fibrosis in animal models and shows promise as an antifibrotic drug for the treatment of systemic scleroderma.

Plasmapharesis

Plasmapheresis, also called "plasma exchange", involves removing blood from the patient and separating the plasma (fluid component of blood) from the blood cells. The plasma, containing immunologically active substances, is then discarded and is replaced with artificial plasma (fluid containing salts and proteins). The artificial plasma together with the blood cells is then returned to the patient's body. Plasmapheresis is performed with a continuous flow machine which removes the patient's blood from one arm and, after the plasma has been separated and replaced with artificial plasma, returns the "new" blood through the other arm. Several small studies have reported that regular plasmapharesis treatments may be effective for the treatment of patients with CREST syndrome, particularly in the early stages of the disease. One small study also reported that plasmapharesis appeared to slow down the progression of severe systemic scleroderma.

Photopheresis

Photopheresis, also called extracorporeal photopheresis and photochemotherapy, is a form of immunotherapy that is used to treat skin problems associated with a certain type of cancer called cutaneous T-cell lymphoma. It is also being investigated as a treatment for other types of diseases including scleroderma.

In general, photopheresis is accomplished as follows:

  • A portion of the patient's blood is removed through a vein.

  • The white blood cells are exposed to ultraviolet A light (UVA) and treated with a drug called 8-methoxypsoralen.

  • The blood is then returned to the patient's body through a vein.

The rationale for using photopheresis for the treatment of scleroderma is to attempt to increase the levels of an enzyme called collagenase which breaks down collagen and, thereby, slows down the rate of collagen production. This procedure is still considered experimental and further studies are required to prove the efficacy of photopheresis before it can be used as a standard treatment for scleroderma.

Autologous Stem Cell Transplantation

Stem cells are primitive blood forming cells found in the bone marrow and peripheral blood that eventually develop into mature red blood cells and white blood cells. Autologous stem cell transplantation is an experimental procedure that is being evaluated for the treatment of systemic scleroderma. This procedure involves first removing stem cells from a patient (either from the bone marrow or peripheral blood) and then storing the stem cells in a freezer until they are returned back to the patient. Once the stem cells have been removed and stored, the patient's own immune system is suppressed using powerful drugs know as immunosuppressants. The stored stem cells are then thawed and returned back into the patient by intravenous infusion. Essentially, this treatment is designed to reverse the "autoimmunity" which is thought to be the primary mechanism responsible for the overproduction of collagen that is characteristic for scleroderma. Although autologous stem cell transplantation has been found to slow down or improve the course of severe systemic scleroderma in some patients, it is still considered an experimental treatment and is also associated with a high mortality rate of about 10%.