PRIMEVIEW

RHEUMATOID ARTHRITIS
For the Primer, visit doi:10.1038/nrdp.2018.1
In most patients, the
pathogenesis of RA begins EPIDEMIOLOGY
Rheumatoid arthritis (RA) is a MECHANISMS years before clinical disease
The modified
chronic, inflammatory, autoimmune proteins is evident
disorder that primarily affects the joints. can trigger an The average prevalence of RA is estimated at
Although this disorder was associated with immune response 0.5–1.0% globally. Genetic factors account for
irreversible joint damage and physical and autoantibody 60% of the risk of developing RA. Variants in
disability in the past, remission is now an formation
the human leukocyte antigen genes (the shared
achievable goal for the majority of patients
epitope) in particular have been shown to be
owing to advances in early diagnosis, new
associated with RA, but >100 risk variants with
drugs and improved treatment strategies.
a weaker association have been identified.
Other important risk factors include female
sex, which increases the risk by twofold, and
MANAGEMENT smoking, particularly in those who are positive
for the shared epitope.
The current treatment strategy for RA is based Stressors An additional
on a treat-to-target approach, which requires trigger hit, such as
Synovial
tight monitoring of the disease activity and post‑translational immune complex
inflammation, BMI
prompt correction of treatment when the target modifications (especially formation, complement
damage to the
is not reached. The current treatment target is citrullination) at mucosal activation or a
sites in susceptible
cartilage and bone
remission or, at the very least, low disease activity. microvascular insult, is
individuals erosion are the likely required to
Disease-modifying antirheumatic drugs (DMARDs) cardinal signs
are able to interfere with the inflammatory develop symptomatic
of RA BMI
disease
process. Methotrexate, a conventional synthetic
DMARD, in combination with short-term, low-
dose glucocorticoids is able to achieve remission
in ~25% of patients with early RA.
When an insufficient response is DIAGNOSIS
Curiously,
achieved, targeted DMARDs —
all targeted
either biological or synthetic
DMARDs are
agents — can be given, No diagnostic criteria exist for RA, but the
equally effective and
usually in combination with an agent with different classification criteria proposed by the ACR/EULAR
methotrexate. In case of immunogenicity but the can inform clinical diagnosis. The classification
Synoviocytes
non‑response, another same mode of action criteria include symptom duration, number and
expand
agent should be used. can be effective in distribution of the joints involved and serological
and produce
non‑responders parameters such as presence of autoantibodies
various cytokines
and proteases, and (that is, rheumatoid factor and anti-citrullinated
adaptive immune protein antibodies) and acute phase reactants
cells infiltrate the (such as C-reactive protein and erythrocyte
synovium sedimentation rate). Importantly, RA does not
QUALITY OF LIFE exclusively affect joints;
TNF
IL-6R The superior clinical outcomes of biological the most common cause of

CD80/CD86 Individuals with RA report a
CD20 lower quality of life (QOL)
than those with type 2 diabetes
JAKs
mellitus, myocardial infarction
$
and hypertension. QOL improves
with lower disease activity,
but decreases with the number
of failed therapies.
DMARDs might offset their high costs, which premature death in individuals
has already decreased in come countries with RA is cardiovascular
with the introduction of biosimilars disease followed by interstitial
lung disease.

Written by Liesbet Lieben; designed by Laura Marshall Article number: 18002; doi:10.1038/nrdp.2018.2; published online 8 Feb 2018
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