RA is a chronic, inflammatory, systemic disease of unkown etiology characteriezed by a symmetric arthrolpathy and variable symptoms outside the joints.
Prevalence between 0.3-2%
prevalence 2.5x higher in women
RA can occur at any age, but peak is between 30-60
worldwide distribution All races affected
some native populations have prevalence as high as 5-6%
family history: first degree relative gives 16x increase in risk
Anti-CCP is a new, sensitive test.
Inflammatory process distinguished from degenerative osteoarthritis in a number of ways,
Hours of morning stiffness
many joints often involved, with symmetry
swelling and warmth in joint
reheumatoid nodules which are squishy, rather than hard like in OA
Boutenierre's and swan-neck deformities can occur over the years.
Approximately 75% of people with RA have a positive RF, though in early disease, the RF can be negative. High levels tend to suggest aggressive disease
Antibodies to cyclic citrillated peptides - proteins that contain citrulline are the target of an autoantibody that is highly specific (up to 97%)for RA. Sensitivities are 50-70%. They can be elevated in early disease when RF is still negative. Antibodies are detected via ELISA.
X-ray
pan carpal disease can result in subluxation of all bones in the joint.
Host susceptibility, likley in interaction with environmental factors, leads to an immune response and chronic inflammation.
Synovium is critical in disease initiation and progression. Synovium in RA undergoes massive tissue proliferation, with high cellularity. The intima undergoes hyperplasia and becomes 5-6 cells thick, while the sub-intima becomes filled with lymphopid cell aggregates. These cells are nearly immuno-competent, with B, T, plasma, and antigen presenting cells.
These cells can directly invade adjacent tissues, including cartilage and bone, resulting in radiographic erosiions, as well as mkae circulating factors: cytokines, prostaglandins, MMPs, etc
Cytokines include:
T-Cells
macrophages/type A synoviocytes
Goals of treatment include slowing progression, treating pain, and preserving function.
RA options: MTX still first-line
Clinical question
Which disease-modifying antirheumatic drugs are more effective and safer for rheumatoid arthritis?
Bottom line
Research guiding the choice of disease-modifying antirheumatic drugs
(DMARDs) for the treatment of rheumatoid arthritis (RA) is incomplete,
and current recommendations are generally made on the basis of
short-term studies and extrapolated studies rather than on the evidence
from any head-to-head comparisons. There is no clear advantage of the
dramatically more expensive new drugs over methotrexate regarding
benefit or adverse effects, though they may offer a benefit when
combination therapy is needed. Specific conclusions regarding
individual and combination treatments are listed in the synopsis below.
(LOE = 1a)
Study design: Systematic review
Funding: Government
Allocation: N/A
Setting: Various (meta-analysis)
Synopsis
Despite an RA prevalence of 2 million patients in the United States
alone, comparative studies that evaluate the relative benefit of
different DMARDs as initial therapy or different combinations are
scant. The researchers conducting this systematic review identified
controlled trials and prospective cohort studies by searching 4
databases, including the Cochrane Library. Two researchers
independently selected studies for inclusion and the results were
abstracted and then validated by a third researcher. They relied on
meta-analyses if already available but did not otherwise combine the
data. The research included the synthetic DMARDs leflunomide,
methotrexate, and sulfasalazine, and also the uber-expensive biologic
antitumor necrosis factor (anti-TNF) agents adalimumab, etanercept, and
infliximab. Most studies were of relatively short duration and enrolled
highly selected populations. Here are their results (with extrapolation
across studies when no direct comparisons exist): Single drug
treatment: - Overall data of low to moderate quality did not identify a
major difference among the synthetic DMARDs, though leflunomide may
offer a slight benefit over sulfasalazine. Rates of adverse effects and
discontinuation rates were similar among the 3 drugs. - Current
research shows no difference among the anti-TNF agents and there is
insufficient study of relative harms to draw any conclusions. As a
group, the anti-TNF agents seem to produce better response than
anakinra. - The anti-TNF agents show no benefit over methotrexate with
regard to clinical outcomes, though they may be more likely to prevent
radiographic progression in patients with early RA (number needed to
treat = 8). Combination therapy: - Starting with combination therapy
with combination synthetic DMARDs offers greater benefits than single
drug or step-up therapy. - Adding prednisone to 1, 2, or 3 synthetic
DMARDS improves clinical response rates and slows progression as
compared with single drug therapy. - Adding methotrexate to anti-TNF
therapy improves clinical response, functional capacity, and quality of
life as compared with either methotrexate alone or anti-TNF treatment
alone..The effect is not the same when sulfasalazine is added to
anti-TNF treatment. - Adding anakinra to etanercept offers no
additional benefit. Combination anti-TNF agents increase adverse
effects.
etanercept
infliximab
Mortality rates in people with RA are higher, though people die of the same types of events.
What's the difference between a rheumatologist and an urologist? In rheumatology, morning stiffness is a bad thing.