What is the typical treatment for rheumatoid arthritis?

Treatment of Rheumatoid Arthritis

Start methotrexate 15-25 mg weekly as first-line therapy, escalate to subcutaneous administration if needed, and add biologic DMARDs (preferably TNF inhibitors initially) only after optimizing methotrexate to maximum tolerated dose for patients with moderate to severe disease activity. 1, 2

Initial Treatment Strategy

• Begin with methotrexate monotherapy at 15-25 mg/week as the anchor DMARD for all newly diagnosed RA patients 1, 3
• Methotrexate can be used alone or combined with other non-biologic DMARDs, glucocorticoids, NSAIDs, or analgesics 4
• Administer folic acid supplementation to reduce gastrointestinal and hematological adverse effects 3

Baseline Laboratory Requirements Before Starting Treatment

• Obtain complete blood count (CBC) and liver function tests prior to initiating therapy 5
• Do not start treatment if absolute neutrophil count (ANC) <2000/mm³, platelets <100,000/mm³, or ALT/AST >1.5× upper limit of normal 5
• Test for latent tuberculosis before starting any DMARD therapy and initiate treatment for latent TB if positive 5, 4

Disease Activity Monitoring and Treatment Targets

• Measure disease activity every 1-3 months using validated indices: SDAI or CDAI 2, 6
• Primary target is remission: SDAI ≤3.3 or CDAI ≤2.8 1, 2, 6
• Alternative acceptable target is low disease activity: SDAI ≤11 or CDAI ≤10 1, 2, 6
• Moderate to high disease activity (SDAI >11 or CDAI >10) requires aggressive treatment escalation 2

Methotrexate Optimization Before Declaring Treatment Failure

This is the most critical step that is frequently missed in clinical practice.

• Increase methotrexate dose to 20-25 mg/week (or maximum tolerated dose) before considering treatment failure 1, 2
• Switch from oral to subcutaneous methotrexate if inadequate response at higher oral doses, as subcutaneous administration has superior bioavailability at doses >15 mg/week 1, 7
• Allow 3-6 months to fully assess efficacy of any new treatment modification 1

Common Pitfall to Avoid

• Do not underdose methotrexate—must reach 20-25 mg/week before concluding inadequate response 2
• Subcutaneous methotrexate can improve disease control and potentially avoid or delay the need for expensive biologic therapy 7

Bridging Therapy with Glucocorticoids

• Administer short-term systemic glucocorticoids at ≤10 mg/day prednisone equivalent for <3 months to bridge until DMARD optimization takes effect 2
• For single-joint involvement, use intra-articular glucocorticoid injection for targeted relief 1, 2
• Critical warning: Do not use long-term glucocorticoids (>1-2 years) as adverse effects (osteoporosis, cataracts, cardiovascular disease) outweigh benefits 2, 6

Treatment Escalation Algorithm for Inadequate Response

If Methotrexate Monotherapy Fails After Optimization (6-12 Months)

For SDAI >11 to ≤26 (moderate disease activity):

• Option 1: Add sulfasalazine + hydroxychloroquine to create triple-DMARD therapy 1, 2
• Option 2: Add a biologic DMARD rather than continuing to adjust conventional DMARDs 2

For persistent moderate to high disease activity:

• Add TNF inhibitor (adalimumab, etanercept, infliximab, etc.) 1, 4
• Add abatacept (CTLA4-Ig, T-cell costimulation modulator) 1
• Add tocilizumab (anti-IL-6 receptor monoclonal antibody) after inadequate response to at least one TNF inhibitor 1, 5
• Add rituximab (anti-CD20) after inadequate response to at least one TNF inhibitor, particularly effective in RF-positive patients 1, 6

Biologic Switching Strategy for Treatment Failures

• Switch to a different mechanism of action rather than trying another TNF inhibitor after first TNF inhibitor failure 2
• For seronegative patients (RF-negative) with inadequate response to TNF inhibitors, prefer abatacept or tocilizumab over rituximab 1
• For seropositive patients (RF-positive), rituximab is particularly effective and should be strongly considered 1, 6

Critical Pitfall to Avoid

• Do not switch within the same biologic class after first failure—change mechanism of action instead 2

Treatment Beyond the First Year

• Continue current DMARD regimen if remission is achieved 1
• Taper and discontinue prednisone once remission is attained 1
• If sustained remission ≥1 year, consider de-escalation of therapy (≤1 trial) 1, 8
• For patients with persistently moderate to high disease activity despite treatment, increase MTX to 20-25 mg/week or switch to subcutaneous administration 1

For Patients on Biologic Therapy with Inadequate Response

• Option 1: Discontinue biologic agent and start triple-DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) 1
• Option 2: Switch to alternative biologic agent with different mechanism of action 1, 2

Contraindications and Safety Monitoring

TNF Inhibitors (Adalimumab, Etanercept, etc.)

• Black box warning: Increased risk of serious infections including tuberculosis, invasive fungal infections, and opportunistic infections 4
• Black box warning: Lymphoma and other malignancies, including hepatosplenic T-cell lymphoma, particularly in adolescent and young adult males receiving concomitant azathioprine or 6-mercaptopurine 4
• Discontinue if serious infection or sepsis develops 4

Tocilizumab (IL-6 Receptor Antagonist)

• Black box warning: Serious infections that may lead to hospitalization or death 5
• Test for latent tuberculosis before use and during therapy (except in COVID-19 patients) 5
• Do not use concomitantly with other biological DMARDs due to increased immunosuppression risk 5

Reassessment Timeline

• Reassess disease activity every 1-3 months during active disease 2, 6
• If no improvement by 3 months after treatment change, adjust therapy—do not wait for 6-month maximal effect before acting 2, 6
• Continue monitoring even after achieving target to detect flares early 2