tender joints, swollen joints, global pain, and
a biomarker for inflammation (either erythrocyte
sedimentation rate (ESR) or CRP). Definitions of
remission or low disease activity vary according
to the measure used. For example, with the
DAS28, remission is a score of <2.6 and low
disease activity is ≤3.2. The previous guideline
did not recommend a specific target other than
agreeing a target with the patient. The revised
guideline now recommends that patients with
active RA are treated with the aim of achieving
a target of remission or low disease activity if
remission cannot be achieved (treat-to-target).
This is more challenging than the
recommendation in 2009 and could have resource
implications as patients might have more
treatment and follow up appointments. The
guideline also recommended that clinicians
should consider making the target remission
rather than low disease activity for people with
an increased risk of radiological progression (that
is, those with positive anti-CCP antibodies or
erosions on X-ray at baseline assessment).
blood tests for acute phase response or
rheumatoid factor. The guideline recommends
referral in any patient when:
• The small joints of the hands or feet are affected
• More than one joint is affected or
• There has been a delay of three months or
longer between onset of symptoms and seeking
medical advice.
Referral should be guided by clinical
examination and should not be delayed by
waiting for results of any investigations as they
may be normal especially in early disease. When
positive, anti-cyclic citrullinated peptide (CCP)
antibodies and/or radiographic erosions at
diagnosis in combination with a raised C-reactive
protein (CRP) are indicators of a poor prognosis.
It is recommended that CCP, CRP and X-rays are
arranged at initial diagnosis in secondary care
if they were not undertaken before referral.
The guideline recommends that the
rheumatologist should inform those with risk
factors of a poor prognosis that they have an
increased risk of radiological progression. This
is in order to emphasise the importance of the
patient monitoring their condition and seeking
rapid access to specialist care if disease worsens
or they have a flare.
RA is a clinical
diagnosis and
patients with
synovitis should
be referred
rapidly to a
rheumatologist
independent
of any
investigations
Treat-to-target strategy
Disease activity can be measured by various tools,
such as the DAS28, which is based on a composite
score from clinical assessment of the number of
Pharmacological management
Initial pharmacological management is led by
specialists. Conventional synthetic disease-
modifying anti-rheumatic drugs (csDMARDs) are
differentiated from targeted synthetic (ts)DMARDs
(such as Janus kinase inhibitors) and biologic (b)
DMARDs (including inhibitors of cytokines such
as tumour necrosis factor and interleukin-6),
which were not within the scope of this guideline.
The previous guideline recommended initial
treatment with a combination of two or more
csDMARDs including methotrexate. However, the
evidence for this approach was re-evaluated and
a meta-analysis did not find superiority for any
individual drug. This is surprising to those who
consider methotrexate to be superior although
this is not supported by current data. Extensive
literature review also did not find superiority for
initial combination compared with a step up
strategy. In contrast to the previous
recommendation, the current guideline therefore
recommends initiation with a single csDMARD
(either sulfasalazine, methotrexate, or
leflunomide) and sequentially adding further
drugs in a step-up approach if the target is not
met. Thereafter, if the patient remains with
severe active disease (DAS>5.1) they would be
eligible for a bDMARD. NICE at present do not
have a recommendation for those who have not
met the target of at least low disease activity and
do not have severe active disease; this is currently
under review because of the reduction in the cost
of some drugs following the introduction of
tsDMARDs and biosimilar bDMARDs.
Once a patient has achieved and maintained
their treatment target of remission or low disease
activity for at least a year without glucocorticoids,
the guideline recommends the rheumatologist
should consider cautiously reducing drug doses or
stopping drugs in a step-down strategy but to
return promptly to the previous DMARD regimen
if the treatment target is no longer met.
Frequency of follow up
What has proved challenging for some
rheumatologists was the recommendation in the
2009 guideline to follow patients monthly until
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