Rheumatoid arthritis

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Understanding this condition

What rheumatoid arthritis is

RA is a systemic autoimmune disease in which synovial inflammation (pannus) drives cartilage and bone erosion via inflammatory cytokines and osteoclast activation. It is frequently seropositive (rheumatoid factor and/or anti-citrullinated protein antibodies) and has extra-articular manifestations. Pathogenesis detail is provided as orientation only and is not sourced on this draft.

Signs and symptoms

Typical presentation is symmetric polyarthritis of the small joints (MCPs, PIPs, wrists, MTPs) with prolonged early-morning stiffness, soft-tissue swelling, and often constitutional symptoms. Persistent synovitis beyond six weeks raises suspicion. Presentation may be atypical (large-joint, palindromic, or seronegative). Not sourced on this draft.

Who gets it, and why

RA affects roughly one in a hundred adults, with a female predominance and a peak onset in mid-adulthood. Risk reflects gene-environment interaction (for example shared-epitope HLA-DRB1 alleles with smoking and other mucosal exposures). Epidemiological figures here are approximate and unsourced on this draft; confirm.

How it is diagnosed

Diagnosis is clinical, supported by serology (RF, anti-CCP), acute-phase reactants (ESR, CRP), and imaging (ultrasound for subclinical synovitis; radiographs for erosions). The ACR/EULAR 2010 classification criteria support case definition in early disease but are classification, not diagnostic, tools. Differential includes psoriatic and other inflammatory arthritides, viral arthritis, and connective-tissue disease. Criteria specifics are summarised separately and are unverified here.

What to expect over time

With early treatment and a treat-to-target approach, a substantial proportion of patients achieve remission or low disease activity and avoid significant erosive damage. Prognostic markers (seropositivity, high acute-phase response, early erosions) inform intensity of therapy. Outcome proportions to be sourced.

Living with and treating it

The goal of treatment

The target is remission or, where remission is not achievable, low disease activity, assessed with a composite measure and reviewed at set intervals with therapy adjusted until the target is sustained. Shared decision-making is central. EULAR 2025 sets sustained remission as the main target, particularly in early disease, with low disease activity an alternative goal in long-standing disease that has already failed one or more DMARD therapies. Where these recommendations say remission, the ACR and EULAR definitions are implied: the Boolean criteria and the index-based criteria (Clinical Disease Activity Index, Simplified Disease Activity Index); the 2022 revision of the Boolean criteria allows a patient global assessment of up to 2 cm rather than 1 cm. EULAR 2025 explicitly discourages DAS28-based remission definitions, because the DAS28 is weighted heavily towards tender joints and acute-phase reactants, and agents that interfere with interleukin-6 signalling (including JAK inhibitors) blunt those reactants and inflate apparent remission rates. On timing, disease activity should be monitored every 1 to 3 months while disease is active; therapy should be adjusted if there is no improvement by at most 3 months after starting treatment, or if the target has not been reached by 6 months. Once the target is sustained, activity monitoring can be less frequent, for example every 6 months or less, provided the person is sufficiently informed about the signs and symptoms of a flare.

Treatments that change the disease

Management is staged: start a csDMARD (methotrexate preferred) with short-term glucocorticoid bridging, then, if the target is not met, add or switch to a bDMARD (for example TNF, IL-6, T-cell, or B-cell directed agents) or a tsDMARD (JAK inhibitor), guided by comorbidity and shared decision-making. NSAIDs are adjuncts for symptom control only. Class choice, sequencing, and safety caveats (for example JAK-inhibitor cardiovascular and malignancy considerations) must be set from primary guidance; unsourced here.

Monitoring and follow-up

Monitoring runs on two tracks. Disease activity: assess every 1 to 3 months while disease is active, adjusting therapy if there is no improvement by at most 3 months or the target is not reached by 6 months, and less often once the target is sustained (about every 6 months or less). Assessment includes clinical examination, especially joint counts, a marker of inflammation such as CRP, and patient-reported information. Drug safety: intervals are agent-specific and are set out on each medication guide rather than restated here, so that one reviewed record drives both the disease guide and the medicine guide. For conventional synthetic DMARDs the ACR schedule, which was defined for rheumatoid arthritis, is a baseline complete blood count, transaminases and creatinine before starting, then every 2 to 4 weeks for the first 3 months, every 8 to 12 weeks from 3 to 6 months, and every 12 weeks beyond 6 months, testing more often after a dose increase. Hepatitis B and C screening applies where risk factors are present. Before a TNF inhibitor, screen for latent tuberculosis with a tuberculin skin test or an interferon-gamma release assay (IGRA preferred after prior BCG vaccination), and for hepatitis B where indicated. See the guide for the specific medicine for its own schedule.

Flares, and what to do

A flare is a period of increased disease activity above the patient's usual controlled state. Management may include short-term glucocorticoid, review of adherence and triggers, and reassessment of the maintenance regimen if flares recur. A flare with fever or a single hot joint warrants exclusion of septic arthritis. Not sourced on this draft.

Living well with RA

Non-drug care complements DMARD therapy: structured exercise and physiotherapy, smoking cessation, weight management, cardiovascular risk-factor optimisation, bone-health attention (especially with glucocorticoid exposure), vaccination per the immunosuppression schedule, and attention to mood and fatigue. Occupational therapy supports joint protection and function. Specific vaccination and bone-protection thresholds to be sourced.

Looking after the rest of you

Comorbidity screening and management are integral: cardiovascular risk (inflammation-driven, warranting active risk-factor management), infection risk on immunosuppression, osteoporosis (glucocorticoid-related), and screening for depression and interstitial lung disease where indicated. The Canadian Rheumatology Association living RA guideline carries this as a practice statement rather than a graded recommendation: people with rheumatoid arthritis should receive preventative care and screening tailored to individual risk factors, with strategies including vaccinations, osteoporosis prevention, physical activity, cardiovascular risk screening, age-appropriate cancer screening, and smoking cessation, tailored to provincial or national guidelines where available. Primary care is often most directly involved in delivering these, while the rheumatologist is often best placed to identify where an individual's risk is elevated. For interstitial lung disease, the ACR 2023 guideline covers rheumatoid arthritis among the systemic autoimmune rheumatic diseases at greatest risk: in people at increased risk it conditionally recommends screening with pulmonary function tests, conditionally recommends screening with HRCT of the chest, and conditionally recommends HRCT plus PFTs over PFTs alone. It conditionally recommends against screening with 6-minute walk distance, chest radiography, ambulatory desaturation testing, or bronchoscopy, and strongly recommends against screening with surgical lung biopsy. Where ILD is established, it conditionally recommends monitoring with PFTs. The guideline does not set a screening interval; cadence remains a clinical judgement.

What to expect at your rheumatology visit

The initial encounter establishes the diagnosis, disease activity, prognostic markers, and comorbidities, initiates therapy, and sets the treat-to-target plan with the patient. Structured follow-up is more frequent during induction and escalation. Orientation content; not sourced.

Verified against Aletaha D, et al. 2010 ACR/EULAR classification criteria (Ann Rheum Dis 2010;69:1580-1588, Table 3). Large joints: shoulders, elbows, hips, knees, ankles. Small joints: MCPs, PIPs, second to fifth MTPs, thumb IPs, wrists. The DIP joints, first CMC, and first MTP joints are excluded. Serology: low-positive is above the upper limit of normal but at most 3 times it; high-positive is more than 3 times the upper limit of normal.

Treatment ladder

1. 1

   First step

   Initiate a csDMARD, methotrexate preferred (strongly recommended over hydroxychloroquine or sulfasalazine, and over a bDMARD or tsDMARD as first therapy; ACR 2021). Short-term glucocorticoid bridging diverges by guideline: EULAR 2025 recommends considering short-term glucocorticoids when initiating or changing DMARDs (grade A), whereas ACR 2021 conditionally favours starting a csDMARD without short-term glucocorticoid and strongly advises against longer-term glucocorticoid. Both minimise exposure to the lowest dose for the shortest time.

   Verified: methotrexate first-line and the glucocorticoid positions against ACR 2021 (Tables 1-2) and EULAR 2025 (recommendation 5). Baseline screening and dosing follow the pretreatment and monitoring guidance ACR 2021 defers to (the 2008/2015 ACR guidelines) and the product monograph, to be sourced.

2. 2

   If the goal is not met

   If the target is not reached after an adequate methotrexate trial, optimise the dose and route (a weekly target of at least 15 mg is conditionally recommended; ACR 2021), then combine or proceed to a bDMARD or tsDMARD; leflunomide or sulfasalazine are alternatives.

   Verified against ACR 2021 (Tables 2-4): methotrexate optimisation, dosing, and step-up.

3. 3

   Advanced treatment

   Add or switch to a bDMARD (for example TNF, IL-6, T-cell, or B-cell directed) or a tsDMARD (JAK inhibitor), with agent choice guided by comorbidity, including cardiovascular and malignancy considerations for JAK inhibitors.

   Verified against ACR 2021 (Table 4): addition of a bDMARD or tsDMARD is conditionally recommended over triple therapy for patients not at target on maximal methotrexate, and switching to a different class is conditionally recommended over the same class. JAK-inhibitor cardiovascular and malignancy considerations per the product safety labelling, to be sourced.

4. 4

   When the disease is well controlled

   With the target sustained for at least 6 months, continuation of DMARDs is conditionally recommended over dose reduction; if tapering, gradual dose reduction is conditionally recommended over gradual discontinuation, and gradual over abrupt (ACR 2021). EULAR tapers glucocorticoid first, then the bDMARD or tsDMARD, then the csDMARD.

   Verified against ACR 2021 (Table 5) and EULAR 2025 (tapering sequence).

Guideline recommendations

Key points

Medication guides

Plain-language guides to the medicines used for this condition. Each has a patient and a clinician view.

• Methotrexate
• Sulfasalazine
• Leflunomide
• TNF inhibitors
• JAK inhibitors
• Glucocorticoids
• NSAIDs

Key numbers

• Approximate adult prevalence on the order of one percent; precise figure and population to be sourced.

References

1. Fraenkel L, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939. https://doi.org/10.1002/acr.24596
2. Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2025 update. Ann Rheum Dis. 2026;85:991-1009. https://doi.org/10.1016/j.ard.2025.08.010
3. Aletaha D, et al. 2010 Rheumatoid Arthritis Classification Criteria: an ACR/EULAR collaborative initiative. Ann Rheum Dis. 2010;69:1580-1588. https://doi.org/10.1136/ard.2010.138461
4. Canadian Rheumatology Association living guidelines for the pharmacological management of rheumatoid arthritis with disease-modifying antirheumatic drug therapy (living guideline). https://rheum.ca
5. 2023 American College of Rheumatology Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Disease. Guideline Summary, Tables 1 and 2. https://rheumatology.org/interstitial-lung-disease-guideline
6. Saag KG, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784. Tables 4 and 6. https://doi.org/10.1002/art.23721
7. Singh JA, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26. Table 3. https://doi.org/10.1002/art.39480