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| Biologicals in the
treatment of Ankylosing Spondylitis (AS) and related
diseases |
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Modern methods of gene technology and
biotechnology have provided new treatment options to
fight diseases at their root. Because these medicines
are produced by means of gene technology and are partly
native human substances, they are called biologicals (Enbrel,
Humira, Kineret, Orencia, Remicade and Rituxan).
Some AS therapies, such as non-steroidal
anti-inflammatory drugs and glucocorticoids, work in a
non-specific manner on systems within the body. In
contrast, biologicals target specific molecules in the
immune system that contribute to the AS disease process,
thus aiming to reduce the signs and symptoms of AS and
slow the progression of the disease while minimizing the
non-specific side effects seen with disease-modifying
antirheumatic drugs.
Because any given biological specifically targets only
one of many molecules involved in AS-associated
inflammation, a wide variety of biologicals are being
developed to treat RA. Each of these targets a different
type of molecule involved in the RA disease process.
Some biologicals are genetically engineered to target
cytokines, which are small proteins similar to hormones.
For example, tumour necrosis factor-alpha (TNF-α) and
interleukin-1 (IL-1) are naturally occurring cytokines
that play a major role in the destructive disease
processes of AS. The use of genetically produced
biologicals that inhibit the action of such cytokines
has already proven very successful for the treatment of
this particular disease.
TNF inhibitors (Etanercept (Enbrel),
Infliximab (Remicade), Humira (Adalimumab)
TNF-α served as a target for several of the first
biological agents to be developed and plays an
important role in inflammation and tissue damage. TNF-α
is a soluble protein that is produced mainly by
monocytes and macrophages and can bind to two different
receptors. TNF-α triggers production of other cytokines,
induces endothelial adhesion molecules and hence,
inhibition of TNF-α can have a more global effect on
inflammation than the blockade of other cytokines.
Interleukin inhibitors (Kineret (Anakinra))
Some biologicals are designed to block the activity of
specific types of cytokines called interleukins. The
effects of the two cytokines are often additive or
synergistic. Interleukins are types of cell proteins
that act as 'chemical messengers', causing inflammation
and tissue damage in people with ankylosing spondylitis.
For example, the biological agent called
specifically targets the cytokine called IL-1. IL-1 has
been shown to be a dominant cytokine associated with the
destructive changes characteristic of AS and stimulates
the production of other cytokines that lead to
inflammation. IL-1 also stimulates production of itself,
which drives the inflammatory process forward. Blocking
IL-1 is an important way of reducing the signs and
symptoms of ankylosing spondylitis. Like TNF, IL-1 is a
key pro-inflammatory cytokine in AS with activities that
are very similar to TNF.
T-lymphocyte inhibitor (Orencia (Abatacept))
T-lymphocytes are important cells of the immune system.
Patients with ankylosing spondylitis may have increased
numbers of T-lymphocytes within the joints that are
inflamed. The T-lymphocytes are “activated,” that is,
they multiply and release chemicals that promote the
destruction of tissues surrounding the joints and cause
the signs and symptoms of AS. By attaching to the
protein, abatacept prevents the activation of the
T-lymphocytes and blocks both the production of new
T-lymphocytes and the production of the chemicals that
destroy tissue and cause the symptoms and signs of
arthritis.
B-Cell, CD20 receptor inhibitor (Rituxan
(Rituximab))
Rituxan is an anticancer agent that can also be used
used to treat rheumatoid arthritis when other
biologicals have failed to be effective. The
effectiveness of rituximab is a result of its
temporarily depleting the number of the B-cells, cells
of the immune system which are important in promoting
inflammation in rheumatoid arthritis.
Cautions
All medications have potential side effects whether they
are taken by themselves or in combination with other
herbal, over-the-counter and prescription medications.
It is therefore important for patients to discuss the
benefits and potential side effects of all their
medications with their doctor.
Depending on the biologic prescribed; they are either
given by injection at home or by an intravenous infusion
at a clinic. Side effects occasionally seen with these
medications include mild skin reactions at the injection
site, headaches or dizziness, colds or sinus infections,
and nausea or diarrhea. Your doctor will discuss all of
the other side effects of these medications before he or
she prescribes them.
Biologics work by suppressing your immune system which
can make it slightly harder for you to fight off
infections. Please inform your doctor if you are prone
to frequent infections. It is advisable to stop your
medication and call your doctor if you develop a fever
or if you have or think you have an infection. Before
starting biologics, your doctor should check for other
infections, such as tuberculosis.
Cost
Biologic treatments are costly, and can range anywhere
from $15,000 to over $25,000 per year. Depending on the
type of insurance coverage you have, treatments may be
fully covered or you may be required to share the cost.
Generally, provincial plans or private insurance
companies will require patients to attempt conventional
treatments before they will cover biologics.
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