What is the recommended treatment for rheumatoid arthritis (RA)?

Treatment of Rheumatoid Arthritis

Start methotrexate (MTX) immediately as first-line therapy for all patients with newly diagnosed rheumatoid arthritis, aiming for a treatment target of remission or low disease activity. 1

Initial Treatment Strategy

First-Line DMARD Therapy

• Methotrexate is the preferred initial DMARD for both early RA (disease duration <6 months) and established RA (disease duration ≥6 months) 1
• Start DMARD therapy as soon as the diagnosis of RA is made—do not delay treatment 1
• If MTX is contraindicated or not tolerated early, use sulfasalazine or leflunomide as alternatives 1, 2

Glucocorticoid Bridging Therapy

• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for patients with moderate or high disease activity when starting DMARDs 1
• Use glucocorticoids for the shortest duration possible (<3 months) as "bridge therapy" until DMARDs take effect 1
• Taper glucocorticoids as rapidly as clinically feasible to minimize long-term toxicity 1

Monitoring and Treatment Escalation

Frequency of Assessment

• Monitor disease activity every 1-3 months in patients with active disease 1
• If no improvement by 3 months after starting treatment, adjust therapy 1
• If treatment target (remission or low disease activity) not reached by 6 months, therapy must be adjusted 1

When to Escalate Treatment

For patients failing MTX monotherapy:

• In patients without poor prognostic factors (e.g., no erosions, low inflammatory markers, seronegative): switch to another conventional synthetic DMARD (csDMARD) strategy 1
• In patients with poor prognostic factors (e.g., high disease activity, erosions, seropositivity): add a biologic DMARD (bDMARD) 1

Biologic DMARD Therapy

Indications for Biologics

• Add biologic therapy for patients with moderate to severely active RA who have inadequate response to MTX and/or other csDMARDs 1, 3
• Biologic therapy should be used in combination with MTX when possible, as this combination is superior to biologic monotherapy 1

First-Line Biologic Options

The following biologics are appropriate first-line options (in combination with MTX) 1:

• TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab)
• Abatacept 3
• Tocilizumab 4
• Rituximab may be used under certain circumstances, though typically reserved for patients who have failed TNF inhibitor therapy 1, 5

Switching Biologics

• If a first biologic fails, switch to another biologic 1
• If a first TNF inhibitor fails, either try another TNF inhibitor or switch to a biologic with a different mechanism of action (abatacept, tocilizumab, rituximab) 1
• Rituximab is indicated for moderately to severely active RA in patients who have had inadequate response to one or more TNF antagonist therapies 5

Targeted Synthetic DMARDs

• Tofacitinib may be considered after biologic treatment has failed 1

Treat-to-Target Strategy

Treatment Goals

• The treatment target should be remission or low disease activity 1
• Use a targeted approach (adjusting therapy based on disease activity measures) rather than a non-targeted approach 1
• Disease activity should be assessed using standardized measures: SDAI >11 or CDAI >10 indicates moderate disease activity requiring treatment intensification 3

Tapering Therapy in Remission

When to Consider Tapering

• If patient achieves persistent remission after tapering glucocorticoids, consider tapering biologic DMARDs, especially if combined with a csDMARD 1
• In cases of sustained long-term remission (≥1 year), cautious reduction of csDMARD dose may be considered 1, 6
• Tapering should only occur after sustained remission, not simply low disease activity 6

Critical Pitfalls to Avoid

• Do not delay DMARD initiation—early treatment with DMARDs is associated with better long-term outcomes and reduced joint damage 7, 8
• Do not use biologic monotherapy when MTX can be combined—combination therapy is more effective 1
• Do not continue long-term glucocorticoids—use only as short-term bridge therapy due to lack of long-term safety data 1
• Do not maintain patients on biologics when they have achieved sustained low disease activity without documented moderate to severe disease—this leads to unnecessary medication exposure and costs 6
• Do not use combination csDMARD therapy in early RA patients with low disease activity—monotherapy is better tolerated and equally effective 1

Special Considerations

Pre-Treatment Screening

• Screen all patients for hepatitis B (HBsAg and anti-HBc) before initiating biologic therapy, particularly rituximab 5
• Screen for tuberculosis before starting biologic therapy 6
• Obtain baseline complete blood counts before starting treatment 5

Comorbidities

• Consider cost, comorbidities, and medication burden when selecting among treatment options 1
• Hepatitis B, hepatitis C, and tuberculosis infections must be addressed before choosing biologic treatments 7