EULAR guideline on RA
(2022 revised)
Dr Faheem Ul Hasan
MBBS, MPH (Epidemiology, NIPSOM)
PG trainee, Indoor Medicine, MARMCH
Glossary and definitions
Term Definition
Poor prognostic factors Persistently moderate/high disease activity (despite csDMARD)
High APR levels
High swollen joint counts
RF and/or ACPA presence (especially at high levels)
Early erosions
Failure of ≥ 2 csDMARD
Glossary and Definition
Term Definition
Low dose glucocorticoids ≤ 7.5 mg/day prednisolone equivalent
Short term Upto 3 months
Tapering Dose reduction or spacing
May include cessation (tapering to 0)
Discontinuation, cessation, Stopping a particular drug
Stopping
Glossary and definitions
Term Definition
Disease activity states
Remission, sustained remission ACR-EULAR defined
Low disease activity, sustained LDA Validated composite disease activity measure
Moderate, High disease activity Validated composite disease activity measure
Glossary and definitions
DMARD nomenclature
Synthetic csDMARDs Methotrexate, Leflunomide, Sulfasalazine, Hydroxychloroquine
tsDMARDs Tofacitinib, Upadacitinib, filgotinib, baricitinib
Biological Biological TNFi: infliximab, adalimumab, etanercept, golimumab, certolizumab
originator IL-6Ri: sarilumab, tocilizumab
DMARDs Co-stimulation-i:abatacept
Anti-CD20: rituximab
Biosimilar Adalimumab, Etanercept, Infliximab, Rituximab
DMARDs
In a Nutshell
• 5 overarching principles
• 11 recommendations
Overarching principles
A Treatment of patients with RA should aim at the best care on a shared decision
between the patient and the rheumatologist
B Treatment decisions are based on disease activity, safety issues and other patient
factors, such as comorbidities and progression of structural damage
C Rheumatologist are the specialists who should primarily care for patients with RA
D Patients require access to multiple drugs with different modes of action to address the
heterogeneity of RA; they may require multiple successive therapies throughout life
E RA incurs high individual, medical and societal costs, all of which should be considered
in its management by the treating rheumatologist
Recommendation-1
• Therapy with DMARDs should be started as soon as the diagnosis
of RA is made
compelling clinical Dx
not necessarily full classical picture of RA
debate about management of suspected RA or pre-RA
Recommendation-2
• Treatment should be aimed at reaching a target of sustained
remission or low disease activity in every patient
remission main target in early disease
low disease activity in established RA
undertreatment- a major problem
confounding factors is an issue
attention to every single item in addition to global score before
adapting therapy
ACR/EULAR defined remission criteria
• Index-based definition • Boolean based definition
SDAI ≤ 3.3 TJC ≤ 1
CDAI ≤ 2.8 SJC ≤ 1
(at any time point) CRP ≤ 1 mg/dL
PGA ≤ 2 (on a 0-10 scale)
(at any time point)
Sustained Remission
• Fulfilling index-based or Boolean based remission for ≥ 6 months
Low Disease activity
Indices Score
SDAI >3.3 to ≤11
CDAI >2.8 to ≤10
DAS28 2.6 to 3.2
SDAI and CDAI
• SDAI • CDAI
simplified disease activity clinical disease activity
index index
TJC+SJC+PGA+EGA+CRP TJC+SJC+PGA+EGA
0-100 0-76
DAS 28
DAS28
Recommendation-3
• Monitoring should be frequent in active disease (every 1-3
months); if there is no improvement by at most 3 months after
the start of treatment or the target has not been reached by 6
months, therapy should be adjusted.
Recommendation-4
• MTX should be part of the first treatment strategy.
No preference regarding route of administration in MTX
Opt for sulfasalazine/leflunomide instead if….
Conventional triple therapy with HCQ strongly discouraged
HCQ as monotherapy if at allearly, mild disease and without
poor prognostic factors when other 3 csDMARDs not applicable
initial dose and loading dose of csDMARDs as before
Dosing of csDMARDs
Drugs Initial Dose Dose escalation Maintenance dose/
Maximum dose
MTX 15mg/wk 25mg/wk 25mg/wk
SSZ 500mg/day 500mg weekly/twice 2000-4000 mg/day
weekly
Leflunomide 20mg/day 20mg/day 20mg/day
HCQ not recommended unless compelled
Recommendation-5
• In patients with a contraindication to MTX (or early intolerance),
leflunomide or sulfasalazine should be considered as part of the
(first) treatment strategy.
Methotrexate essentials
Contraindicaton Side Effects
Chronic hepatitis (any form) Gastric irritation, stomatitis,
Significant kidney dysfunction nausea, vomiting, malaise
(most common)
(eGFR <30 mL/min/1.73m
square) Cytopenias
Pregnancy Hepatotoxicity
Hypersensitivity pneumonitis
Teratogenic
Recommendation-6
• Short term GCs should be considered when initiating or changing csDMARD,
in different dose regimens and routes of administration, but should be
tapered and discontinued as rapidly as clinically feasible.
role in bridge therapy and transient flare
in real life, chronic GC therapy seen upto 60% patients
inability to discontinue GC due to persistently active disease imply absence of
“sufficient effectiveness” of current DMARD
any dependence on GC for > 4 months indicates “definitive failure of
respective DMARD”
Glucocorticoids in bridging therapy of RA
• During initiating or changing csDMARDs
• Either single parenteral dose (i.e. IM methylprednisolone) or oral
regimen with a predefined tapering and discontinuation scheme
not spanning > 3 months
• Should be discontinued rapidly in case of bDMARD or tsDMARD
initiation
Glucocorticoids in RA flare
• Local injections preferable in mono or oligoarticular transient
flare
• Persistent, polyarticular flare should begs reassessment of DMARD
Chronic GC in RA – Points to ponder
• Self medication in high doses and abrupt reduction further
flaring jeopardise success rate of additional options
• Resource poor settings and financial accessibility is an issue
• Low dose GC over 2 years not only efficacious but also beneficial
in elderly patients. Major safety concerns occurred > 5 years of
use (GLORIA trial)*
*long term data pending
Recommendation-7
• If the treatment target is not achieved with the first csDMARD
strategy, in the absence of poor prognostic factors, other
csDMARDs should be considered.
remains unchanged
conventional triple therapy not advocated but also not strongly
recommended against
Recommendation-8
• If the treatment target is not achieved with the first csDMARD
strategy, when poor prognostic factors are present, a bDMARD
should be added; JAK inhibitors may also be considered, but
pertinent risk factors* must be taken into account.
Phase II considerations
Poor prognostic factors • MACE RF: Age >65,
current/past smoking, DM,
• RF/ACPA, esp at high levels
HTN, obesity
• High disease activity • Malignancy RF: Current/past
• Early joint damage history of malignancy,
• Failure of ≥ 2 csDMARDs • Thomboembolic RF: MI, HF,
COCP, HRT,
Recommendation-9
• bDMARDs and tsDMARDs* should be combined with a csDMARD;
in patients who can not use csDMARD as co-medication, IL-6
pathway inhibitors and tsDMARDs may have some advantages
compared with other bDMARDs.
once the patient at this stage, they usually have tolerated MTX
well, so no need to stop the drug due to intolerance
MTX can be reduced to as low as 10 mg weekly
Recommendation-10
• If a bDMARD or tsDMARD has failed, treatment with another
bDMARD or a tsDMARD should be considered; if one TNF or IL-6
receptor inhibitor therapy has failed, patients may receive an
agent with another mode of action or a second TNF or IL-6
receptor inhibitor.
sarilumab proved efficacious in case tocilizumab failed
efficacy and safety data of using a JAKi after a failed JAKi is still
missing (research agenda)
failed multiple b/tsDMARD diffiucult-to-treat RA
Recommendation-11
• After glucocorticoids have been discontinued and a patient is
in sustained remission, dose reduction of DMARDs
(bDMARDs/tsDMARDs and/or csDMARDs) may be considered.
no difference in clinical outcome when either a bDMARD or csDMARD
was tapered first
no preferred tapering sequence, but left to the discretion of patients
and rheumatologist
stopping bDMARDs and/or csDMARDs leads to flare in most patients
Recommendation-11 (continued)
• Most patients who flared after dose reduction, can be brought
back into a good disease state after re-introduction of the original
dose.
Criticisms
• Management of Pre-RA
• Optimum management of refractory RA (this population is
increasing in number)
Some research agenda
• Frequency of chronic GCs in RA patients in resource poor countries
and way of mitigation
• Effectiveness and safety profiles of repeated IM glucocorticoids
• MACE and malignancy risk in pan-JAKi vs selective JAKi
Take home message
• Treat-to-target strategy
• Short term GC
• Conventional triple therapy discouraged (when HCQ included)
• Dose reduction or interval increase in sustained remission
• bDMARD preferred over JAKi in patients with RF for malignancy or
MACE
• Contextual consideration
? Is Pre-RA
• Seven parameters
symptoms of MCP joints
morning stiffness >60 min
1st degree relative
difficulty making fist
(+) squeeze test of MCP joints
most severe symptom in early morning
symptom duration <1 year
