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Rheumatoid Arthritis:Emerging Treatments

Rheumatoid Arthritis:Emerging Treatments

Rheumatoid arthritis (RA) affects 1% of
adults during their most productive
years and can result in significant disability.
The goals of therapy are to reduce
pain, limit joint destruction, and
preserve function.

In recent years, the armamentarium
of agents that combat RA has greatly
expanded. New biologic therapies
that specifically target the immune response
are now available. Although disease-
modifying antirheumatic drugs
(DMARDs) such as methotrexate remain
the standard of care, these newer
agents can be added to the regimen
when monotherapy fails.

In this article, I offer general
guidelines for selecting the safest and
most effective regimens for your patients
with RA. I also describe how to
make best use of the newer therapies.

OVERVIEWEpidemiology.Women are affected
by RA about 3 times as often as
men. The presence of estrogen receptors
on synovial cells and T cells suggests
an important hormonal relationship.
Estrogens influence both T-cell
survival and cytokine production.1
This relationship between estrogen
and immune disease may explain the
increased prevalence of RA in women.

RA appears to be genetically
linked, with higher concordance in
monozygotic than dizygotic twins.2
One genotype of HLA-DRB chains appears
to be a marker for RA.3 Approximately
10% of patients with RA have an
affected first-degree relative.

Pathophysiology. RA is characterized
by synovial inflammation and
progressive erosion of cartilage and
bone. The process begins with the activation
of T cells, which results in proliferation
of synovial cells, activation of
proinflammatory cells from the bone
marrow, and secretion of cytokines (including
interleukin [IL]-1 and tumor
necrosis factor α [TNF-α]) by macrophages
and fibroblast-like synovial
cells.4 Many therapies for RA-including
corticosteroids and TNF and IL-1
antagonists-directly inhibit proinflammatory
cytokine activities.

Disease progression. Symptoms
of RA typically develop between the
third and sixth decades of life. Significant
joint abnormality and disability
occur within the first few years of disease.
5,6 Eighty-three percent of patients
with RA experience joint-space narrowing,
and 67% have joint erosions with-
in the first 2 years (Figure).2 After 5
years, joint erosions can be seen radiographically
in 73% of patients.7 After 18
years, all patients have joint-space narrowing,
97% have joint erosions, and
41% have malalignment.7

Economic impact. Patients with
RA begin to incur significant costs
early in the course of illness. A study of
patients with newly diagnosed active
RA that evaluated costs during the first
6 months of illness showed that medical
costs averaged $200 a month.8,9 Patients
lost an average of 3.8 workdays
monthly, at an indirect cost of $281.10
Eighteen percent became work-disabled
during the first 6 months of illness.
Work disability increased to
about 60% after 10 years of illness.10

  Table 1 –American College of Rheumatology classification
criteria for acute rheumatoid arthritis*
Morning stiffness of joints lasting ≥ 1 h
Soft tissue swelling or fluid at 3 or more joints
Swelling or fluid in hand joints
Simultaneous arthritic changes in symmetric joints
Subcutaneous nodules
Positive serum rheumatoid factor
Joint erosions or decalcification on radiographs
 

*A positive diagnosis requires 4 of the above criteria. Criteria 1 - 4 must be present for at least 6 weeks.
Adapted from Arnett FC et al. Arthritis Rheum. 1988.11

INITIAL EVALUATION

The American College of Rheumatology
(ACR) classification criteria (Table
1) can help guide clinical diagnosis.11
Laboratory testing is also useful in diagnosis,
as well as in assessing prognosis
and in monitoring the response to therapy.
Rheumatoid factor-autoantibodies
found in most patients with RA-may
also be present in other rheumatologic
conditions (eg, lupus erythematosus and
Sjgren syndrome) and infectious illnesses
(eg, malaria and rubella). A high
rheumatoid factor titer in patients with
RA is associated with more aggressive
disease, greater joint destruction, and
greater functional disability.12,13 The Creactive
protein (CRP) level and erythrocyte
sedimentation rate (ESR) are markers
of the acute phase response. Elevations
in CRP level and ESR also correlate
with bone destruction.14

Evaluation includes an assessment
of comorbid illness and lifestyle
factors that may aggravate RA (Algorithm).
Frequently associated comorbid
conditions that may be exacerbated
by either the pathophysiologic
mechanisms that underlie RA or by its
treatment include infection, renal insufficiency,
cardiovascular disease,
chronic pulmonary disease, peptic
ulcer disease, and lymphoproliferative
disease.15,16 Psychological distress also
increases disability associated with RA;
symptoms of anxiety, depression, and
hopelessness need to be identified and
treated.17-19

Cigarette smoking is associated
with an increased risk of RA. Longer
duration of smoking is linked to
greater risk, and heavier use is associated
with more serious symptoms and
bony erosions.20-22 Obesity is also a risk
factor, since adipose tissue releases
proinflammatory substances, including
IL-6, TNF-α, and CRP.23

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