This document provides guidelines from the 2021 American College of Rheumatology for the treatment of rheumatoid arthritis. It discusses the diagnostic criteria and pathogenesis of rheumatoid arthritis. It recommends methotrexate monotherapy as first-line treatment for patients with moderate to high disease activity. It provides guidance on modifying or switching treatment for patients not achieving treatment targets. It also offers recommendations for treating specific patient populations and managing safety concerns.

1. By dr wafa sheikh
Consultant family medicine
2021 American College of Rheumatology Guideline
for the Treatment of Rheumatoid Arthritis
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Rheumatoid arthritis
•Rheumatoid arthritis is a chronic inflammatory disorder
characterised by a chronic polyarthritis that primarily affects the peripheral joints and related
periarticular tissues.
• It usually starts as an insidious symmetric polyarthritis, often with non-specific systemic
symptoms.
• Diagnostic criteria include arthritis lasting longer than 6 weeks (although evidence suggests
that 12 wks is more specific), positive rheumatoid factor, and radiological damage.
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Rheumatoid arthritis
• INCIDENCE/PREVALENCE
• Prevalence ranges from 0.5-1.5% of the population in industrialised countries.
• Rheumatoid arthritis occurs more frequently in women than men (ratio 2.5 : 1).
• The annual incidence in women was recently estimated at 36/100 000 and in men at 14/100
000.
• AETIOLOGY/RISK FACTORS
• The evidence suggests that the cause is multifactorial in people with genetic susceptibility.
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4. 2010 American College of Rheumatology/European
league against Rheumatism classification criteria for RA
1-Patient who has al least one with definite clinical synovitis
2-With synovitis no better explain by other disease
Classification criteria for RA(score based algorithm add score of category A through D Score
A score more or equal 6 out of 10 (definite RA )
A Joint involvement
One large joint 0
2-10 large joint 1
1-3 small joint (with or without involvement of large joint) 2
4-10 joints 3
More than 10 joints(at least one small joint) 5
B Serology at least one test result needed for the classification
Negative RF and ACPA 0
at least one test result needed for the classification 2
High positive RF and positive ACPA 3
C Acute phase reactant at least one test result needed for the classification
Normal CRP and Normal ESR 0
Abnormal CRP and Normal ESR 1
D. Duration of symptoms
<6 weeks 0
> or = 6 weeks 1
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Deforming arthritis characterized by ulnar deviation and swan
neck deformities & Swelling of the metacarpophalangeal joints .
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7. Refer to the Specialist
• Refer for specialist opinion any adult with suspected persistent synovitis of
undetermined cause.
• Refer urgently (even with a normal acute-phase response, negative anti-cyclic
citrullinated peptide [CCP] antibodies or rheumatoid factor) if any of the following
apply:
• The small joints of the hands or feet are affected
• More than one joint is affected
• There has been a delay of 3 months or longer between onset of symptoms and
seeking medical advice. [2009, amended 2018]
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8. • As soon as possible after establishing a Diagnosis of RA:
• Measure anti-CCP antibodies, unless already measured to inform diagnosis
• X-ray the hands and feet to establish whether erosions are present, unless X-
rays were performed to inform diagnosis
• Measure functional ability using the Health Assessment Questionnaire
(HAQ), to provide a baseline for assessing the functional response to
treatment. [2018]
• If anti-CCP antibodies are present or there are erosions on X-ray:
• Advise the person that they have an increased risk of radiological progression
rapid access to specialist care if disease worsens or they have a flare. [2018]
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Radiological changes
• Plain Radiographs
• To be detected by plain radiography, erosions must have
eroded through the cortex of the bone around the margins of
the MCP and PIP joint & can be identified by plain radiography
in 15 to 30 percent of patients in the first year of the disease.
• Magnetic Resonance Imaging (MRI)
• A more sensitive technique than plain radiography .
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Normal
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• Tenosynovitis & synovitis
• Synovial cysts
• Displaced/ ruptured tendons
• Bony erosions ***Hallmark***
Lateral view of the elbow in a
patient with rheumatoid arthritis
(RA) reveals
soft tissue swelling and
osteopenia with destruction of the
elbow joint.
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Radiology
• Marginal cortical erosions
• Subluxation/dislocation lesser MPJ
• Joint space narrowing
• Well marginated spur
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Laboratory markers Rheumatoid Arthritis (RA)
• Rheumatoid factor titers rarely change with disease activity,
and are not useful for following patients with RA, although whether
or not a patient's rheumatoid factor is positive is helpful in
determining prognosis .
• Anti-cyclic citrullinated peptide (CCP) Antibodies , a post-
translationally modified amino acid created by deimination of
arginine residues, may be as sensitive and more specific than
assays for RF for the diagnosis of RA. may be a better predictor
of progression to erosive joint disease than RF titers early in the
course of RA .
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17. Clinical Evidence Rheumatoid Arthritis
Beneficial
• Antimalarials
• Early intervention with DMARDs
• Methotrexate
• Minocycline
• Short term low dose oral corticosteroids
• Sulfasalazine
Likely to be beneficial
• Auranofin (less effective than other
DMDRDs)
• Leflunomide (long term safety unclear)
• Treatment with several disease modifying
antirheumatic drugs combined
• Tumour necrosis factor antagonists (long
term safety unclear)
Trade off between benefits and harms
• Azathioprine
• Ciclosporin
• Cyclophosphamide
• Long term low dose oral corticosteroids
• Parenteral gold
• Penicillamine
systematic reviews & subsequent RCTS has
found that these drugs significantly reduces
disease activity and joint inflammation, improves
functional status, and may decrease the rate of
radiological progression but Common and
potentially serious adverse effects limit the
usefulness of these drugs.
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18. Recommendations for DMARD-naive patients with
moderate-to-high disease activity (Table 2)
• DMARD monotherapy Methotrexate is strongly recommended over
hydroxychloroquine or sulfasalazine for DMARD naive patients with
moderate-to-high disease activity
• Methotrexate is conditionally recommended over leflunomide for
DMARD-naive patients with moderate-to-high disease activity
• Methotrexate monotherapy is strongly recommended over bDMARD
or tsDMARD monotherapy for DMARD-naive patients with moderate-
to-high disease activity
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19. Recommendations for DMARD-naive patients with
moderate-to-high disease activity (Table 2)
• Methotrexate monotherapy is conditionally recommended over dual
or triple csDMARD therapy for DMARD-naive patients with moderate-to-
high disease activity
• Methotrexate monotherapy is conditionally recommended over
methotrexate plus a tumor necrosis factor (TNF) inhibitor for DMARD-
naive patients with moderate-to-high disease activity
• Methotrexate monotherapy is strongly recommended over
methotrexate plus a non–TNF inhibitor bDMARD or tsDMARD for
DMARD-naive patients with moderate-to-high disease activity
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20. Recommendations for DMARD-naive patients with
moderate-to-high disease activity (Table 2)
• Glucocorticoids Initiation of a csDMARD without short-term
(<3month) glucocorticoids conditionally recommended over initiation of
csDMARD with short term glucocorticoid DMARDS-naïve patient with
moderate to high disease activity .
• Initiation of a csDMARD without longer-term (≥3 months)
glucocorticoids is strongly recommended over initiation of a csDMARD
with longer-term glucocorticoids for DMARD-naive patients with
moderate-to-high disease activity.
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21. Recommendations for DMARD-naive patients with low
disease activity (Table 2)
• Hydroxychloroquine is conditionally recommended over other
csDMARDs, sulfasalazine is conditionally recommended over
methotrexate, and methotrexate is conditionally recommended over
leflunomide for DMARD naive patients with low disease activity .
• Methotrexate monotherapy is conditionally recommended over the
combination of methotrexate plus a bDMARD or tsDMARD .
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22. Recommendations for administration of methotrexate
(Table 3)
• Oral methotrexate is conditionally recommended over subcutaneous
methotrexate for patients initiating methotrexate
• Initiation/titration of methotrexate to a weekly dose of at least 15 mg within
4 to 6 weeks is conditionally recommended over initiation/ titration to a
weekly dose of
• A split dose of oral methotrexate over 24 hours or weekly subcutaneous
injections, and/or an increased dose of folic/folinic acid, is conditionally
recommended over switching to alternative DMARD(s) for patients not
tolerating oral weekly methotrexate
• A split dose of oral methotrexate over 24 hours or weekly subcutaneous
injections, and/or an increased dose of folic/folinic acid, is conditionally
recommended over switching to alternative DMARD(s) for patients not
tolerating oral weekly methotrexate.
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23. Recommendations for treatment modification in patients
treated with DMARDs who are not at target (Table 4)
• Treat-to-target
• A treat-to-target approach is strongly recommended over usual care for
patients who have not been previously treated with bDMARDs or
tsDMARDs
• A treat-to-target approach is conditionally recommended over usual
care for patients who have had an inadequate response to bDMARDs or
tsDMARDs
• A minimal initial treatment goal of low disease activity is conditionally
recommended over a goal of remission
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24. Recommendations for treatment modification in patients
treated with DMARDs who are not at target (Table 4)
• Modification of DMARD(s) Addition of a bDMARD or tsDMARD is
conditionally recommended over triple therapy (i.e., addition of sulfasalazine
and hydroxychloroquine) for patients taking maximally tolerated doses of
methotrexate who are not at target
• Switching to a bDMARD or tsDMARD of a different class is conditionally
recommended over switching to a bDMARD or tsDMARD belonging to the
same class for patients taking a bDMARD or tsDMARD who are not at target
• Use of glucocorticoids Addition of/switching to DMARDs is conditionally
recommended over continuation of glucocorticoids for patients taking
glucocorticoids to remain at target
• Addition of/switching to DMARDs (with or without intraarticular [IA]
glucocorticoids) is conditionally recommended over the use of IA
glucocorticoids alone for patients taking DMARDs who are not at target.
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25. Recommendations for tapering/discontinuing DMARDs (Table 5)
• Gradual discontinuation of sulfasalazine is conditionally
recommended over gradual discontinuation of hydroxychloroquine for
patients taking triple therapy who wish to discontinue a DMARD.
• Gradual discontinuation of methotrexate is conditionally
recommended over gradual discontinuation of the bDMARD or
tsDMARD for patients taking methotrexate plus a bDMARD or tsDMARD
who wish to discontinue a DMARD .
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26. Recommendations for specific patient populations (Table 6)
• Subcutaneous nodule
• Methotrexate is conditionally recommended over alternative
DMARDs for patients with subcutaneous nodules who have moderate-to
high disease activity .
• Switching to a non-methotrexate DMARD is conditionally
recommended over continuation of methotrexate for patients taking
methotrexate with progressive subcutaneous nodules.
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27. Recommendations for specific patient populations (Table 6)
• Heart failure
• Addition of a non–TNF inhibitor bDMARD or tsDMARD is conditionally
recommended over addition of a TNF inhibitor for patients with New
York Heart Association (NYHA) class III or IV heart failure and an
inadequate response to csDMARDs .
• Switching to a non–TNF inhibitor bDMARD or tsDMARD is conditionally
recommended over continuation of a TNF inhibitor for patients taking a
TNF inhibitor who develop heart failure.
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28. Recommendations for specific patient populations (Table 6)
• Pulmonary disease Methotrexate is conditionally recommended over
alternative DMARDs for the treatment of inflammatory arthritis for
patients with clinically diagnosed mild and stable airway or parenchymal
lung disease, or incidental disease detected on imaging, who have
moderate-to-high disease activity
• Lymphoproliferative disorder Rituximab is conditionally recommended
over other DMARDs for patients who have a previous
lymphoproliferative disorder for which rituximab is an approved
treatment and who have moderate-to-high disease activity
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29. Recommendations for specific patient populations (Table 6)
• Hepatitis B infection Prophylactic antiviral therapy is strongly recommended
over frequent monitoring of viral load and liver enzymes alone for patients
initiating rituximab who are hepatitis B core antibody positive (regardless of
hepatitis B surface antigen status)
• Prophylactic antiviral therapy is strongly recommended over frequent
monitoring alone for patients initiating any bDMARD or tsDMARD who are
hepatitis B core antibody positive and hepatitis B surface antigen positive
• Frequent monitoring alone of viral load and liver enzymes is conditionally
recommended over prophylactic antiviral therapy for patients initiating a
bDMARD other than rituximab or a tsDMARD who are hepatitis B core
antibody positive and hepatitis B surface antigen negative
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30. Recommendations for specific patient populations (Table 6)
• Nonalcoholic fatty liver disease (NAFLD) Methotrexate is conditionally
recommended over alternative DMARDs for DMARD-naive patients with
NAFLD, normal liver enzymes and liver function tests, and no evidence
of advanced liver fibrosis who have moderate-to-high disease activity.
• Persistent hypogammaglobulinemia without infection In the setting of
persistent hypogammaglobulinemia without infection, continuation of
rituximab therapy for patients at target is conditionally recommended
over switching to a different bDMARD or tsDMARD.
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31. Recommendations for specific patient populations (Table 6)
• Previous serious infection Addition of csDMARDs is conditionally
recommended over addition of a bDMARD or tsDMARD for patients
with a serious infection within the previous 12 months who have
moderate-to-high disease activity despite csDMARD monotherapy
• Addition of/switching to DMARDs is conditionally recommended over
initiation/dose escalation of glucocorticoids for patients with a serious
infection within the previous 12 months who have moderate-to-high
disease activity
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32. • Nontuberculous mycobacterial (NTM) lung disease
• Use of the lowest possible dose of glucocorticoids (discontinuation if
possible) is conditionally recommended over continuation of
glucocorticoids without dose modification for patients with NTM lung
disease .
• Addition of csDMARDs is conditionally recommended over addition of a
bDMARD or tsDMARD for patients with NTM lung disease who have
moderate-to-high disease activity despite csDMARD monotherapy .
• Abatacept is conditionally recommended over other bDMARDs and
tsDMARDs for patients with NTM lung disease who have moderate-to
high disease activity despite csDMARDs .
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Recommendations for specific patient populations (Table 6)
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33. Initial pharmacological management Conventional
Disease-Modifying Anti-Rheumatic drugs
• For adults with newly diagnosed active RA:
• Offer first-line treatment with DMARDs monotherapy using oral
methotrexate, leflunomide or sulfasalazine as soon as possible and ideally
within 3 months of onset of persistent symptoms.
• Consider hydroxychloroquine for first-line treatment as an alternative to oral
methotrexate, leflunomide or sulfasalazine for mild or palindromic disease.
• Consider short-term bridging treatment with glucocorticoids (oral,
intramuscular or intra-articular) when starting a new DMARDs. [2018]
Rheumatoid arthritis in adults: management (NICE 2021).
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34. dr wafa sheikh 34
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35. Rheumatoid arthritis in adults: management(NICE) 2018
NICE guideline Published: 11 July 2018
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Rheumatoid arthritis
Prognosis :
• The course of rheumatoid arthritis is variable and unpredictable.
• Some people experience flares and remissions, and others a progressive
course.
• Over the years, structural damage occurs, leading to articular deformities and
functional impairment.
• About half of people will be unable to work within 10 years.
• Rheumatoid arthritis shortens life expectancy.
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37. Thank you
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