What is the treatment for rheumatoid arthritis?

Treatment of Rheumatoid Arthritis

Start methotrexate immediately at 15 mg weekly with folic acid 1 mg daily as first-line therapy for all newly diagnosed rheumatoid arthritis patients, escalating to 20-25 mg weekly or maximum tolerated dose within 3 months if disease activity persists. 1, 2

Initial Treatment Strategy

First-Line DMARD Therapy

• Methotrexate monotherapy is the preferred initial treatment for most patients with newly diagnosed rheumatoid arthritis, with or without short-term glucocorticoids 1, 2
• Start at 15 mg weekly and escalate to 20-25 mg weekly (or maximum tolerated dose) based on response 1, 2
• Add folic acid 1 mg daily to reduce methotrexate toxicity 1
• Lower doses may be required in elderly patients or those with chronic kidney disease 1

Alternative First-Line Options

• For patients with contraindications to methotrexate, use hydroxychloroquine, sulfasalazine, or leflunomide as alternative conventional synthetic DMARDs 2
• Short-term glucocorticoids (≤1-2 years) may be added during initial treatment or disease flares, but long-term use should be avoided due to risks of cataracts, osteoporosis, and cardiovascular disease 2

Critical Timing for Assessment

• Evaluate disease activity at 3 months using composite measures (SDAI, CDAI, or DAS28) to determine if treatment escalation is needed 1
• More than 75% of patients who achieve low disease activity or remission at 3 months will be in remission at 1 year 1
• If low disease activity is not achieved by 3 months, immediately escalate therapy 1, 2

Treatment Escalation Algorithm

Step 1: Inadequate Response to Methotrexate Monotherapy

• Add sulfasalazine and hydroxychloroquine to methotrexate (triple therapy) as the next step for patients not achieving low disease activity 1, 2
• This combination is preferred over immediate biologic therapy based on cost-effectiveness and comparable efficacy when using tight control strategies 1

Step 2: Persistent Moderate to High Disease Activity

• Add a biologic DMARD or targeted synthetic DMARD if disease activity remains moderate to high despite optimized conventional synthetic DMARDs 1, 2
• Continue methotrexate as background therapy when adding biologics 1, 2

Biologic Selection Strategy

First Biologic Choice:

• TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab, golimumab) are the preferred first biologic agents after conventional DMARD failure 2, 3
• Adalimumab is dosed at 40 mg subcutaneously every other week for rheumatoid arthritis 3
• TNF inhibitors can be used alone or in combination with methotrexate or other non-biologic DMARDs 3

Alternative First Biologics:

• IL-6 receptor antagonists (tocilizumab, sarilumab) are effective as monotherapy or combined with methotrexate 2
• T-cell costimulation modulator (abatacept) is an option for first biologic therapy 2
• JAK inhibitors (tofacitinib, baricitinib) are newer oral targeted synthetic DMARDs with efficacy comparable to biologics 2

Step 3: Inadequate Response to First TNF Inhibitor

• Switch to a different TNF inhibitor (effective in 50-70% of cases) OR switch to a non-TNF biologic with different mechanism of action 2
• Non-TNF options include abatacept, tocilizumab, rituximab, or JAK inhibitors 2

Step 4: Sequential Biologic Failures

• After failure of both a TNF inhibitor and abatacept, switch to rituximab for patients with high disease activity or moderate disease activity with poor prognostic features 2
• Rituximab is indicated specifically for patients who have had inadequate response to one or more TNF antagonists 2, 4
• Rituximab is dosed in combination with methotrexate for moderately to severely active rheumatoid arthritis 4

Biomarker-Guided Treatment Selection

Predicting Response to Specific Biologics

• Patients who are rheumatoid factor positive, anti-CCP positive, or have elevated serum IgG respond better to rituximab 1, 2
• Seronegative patients may respond better to abatacept or tocilizumab 2
• These biomarkers should guide biologic selection after TNF inhibitor failure 2

Treatment Goals and Monitoring

Target Disease Activity

• Aim for remission or low disease activity (CDAI ≤10 or SDAI ≤11) as the primary treatment goal 1, 2
• Use composite disease activity measures (SDAI, CDAI, or DAS28) rather than individual assessments 1
• Monitor disease activity every 1-3 months and adjust therapy if targets are not met 1

Long-Term Goals

• Prevent joint destruction and structural damage 1
• Prevent comorbidities including cardiovascular disease and osteoporosis 1
• Preserve independence, work ability, and quality of life 1

Treatment De-escalation in Sustained Remission

Criteria for Tapering

• Consider cautious de-escalation only after sustained remission for ≥1 year 2, 5
• Approximately 15-25% of patients may achieve sustained drug-free remission 2
• Predictors of successful tapering include shorter symptom duration, absence of rheumatoid factor or anti-CCP antibodies, lower disease activity before remission, and less baseline disability 2

Special Considerations and Safety Monitoring

Pre-Treatment Screening

• Screen all patients for tuberculosis (TST or IGRA) before starting biologic therapy, regardless of risk factors 2, 3, 4
• Screen for hepatitis B and C before initiating biologics; do not use rituximab in untreated chronic hepatitis B 2, 4
• Obtain complete blood counts with differential and platelets before starting therapy 4

Contraindications and Cautions

• Avoid specific biologics in patients with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, or nontuberculous mycobacterial lung disease 2
• TNF inhibitors carry increased risk of serious infections, tuberculosis reactivation, and malignancy including lymphoma 3
• Rituximab carries risks of fatal infusion reactions, hepatitis B reactivation, and progressive multifocal leukoencephalopathy 4

Ongoing Monitoring

• Monitor CBC with differential and platelets at 2-4 month intervals during biologic therapy 2, 4
• Continue monitoring for infections during and after treatment, including possible tuberculosis development in patients who initially tested negative 3

Critical Pitfalls to Avoid

Timing and Escalation Errors

• Delaying DMARD initiation leads to irreversible joint damage and worse long-term outcomes 1
• Inadequate methotrexate dosing (failing to escalate to 20-25 mg weekly) or insufficient trial duration before declaring treatment failure 1, 2
• Failing to adjust therapy when treatment targets are not met at 3-6 month assessments 1, 2

Medication Management Errors

• Long-term glucocorticoid use beyond 1-2 years without appropriate monitoring for adverse effects 2
• Continuing biologic therapy in patients who have achieved sustained low disease activity without meeting criteria for moderate to severe disease 5
• Overlooking comorbidities (hepatitis, tuberculosis, heart failure) that influence treatment selection 2, 3, 4

Strategic Errors

• Using fixed treatment protocols rather than treat-to-target strategies with frequent disease activity monitoring 1
• Failing to refer patients early to rheumatology, as timely intervention reduces disease burden and improves outcomes 1