What is the treatment for rheumatoid arthritis?

Treatment of Rheumatoid Arthritis

Start methotrexate 15-25 mg weekly immediately upon diagnosis as first-line therapy, combined with short-term low-dose glucocorticoids (≤10 mg/day prednisone) for rapid symptom control, with the goal of achieving remission or low disease activity within 6 months. 1, 2

Initial Treatment Strategy

First-Line DMARD Therapy

• Methotrexate is the anchor drug for all newly diagnosed rheumatoid arthritis patients, optimized to 20-25 mg weekly or maximum tolerated dose within the first few weeks 1, 2
• Add folic acid supplementation to reduce methotrexate toxicity 2
• Maintain maximal methotrexate dose (25-30 mg weekly) for at least 3 months before concluding treatment failure 2
• For patients with contraindications to methotrexate (liver disease, significant alcohol use, pregnancy), alternative conventional synthetic DMARDs include leflunomide, sulfasalazine, or hydroxychloroquine 1

Adjunctive Glucocorticoid Therapy

• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) at diagnosis for rapid symptom relief while methotrexate takes effect 1, 2
• Use the lowest possible dose for the shortest duration (less than 3 months) 1, 2
• Taper and discontinue prednisone once remission is achieved 2
• After 1-2 years, long-term corticosteroid risks (cataracts, osteoporosis, fractures, cardiovascular disease) outweigh benefits 3, 1, 2

Treatment Targets and Monitoring

Define Your Goals

• Primary target: Clinical remission defined as SDAI ≤3.3 or CDAI ≤2.8 1, 2
• Acceptable alternative: Low disease activity (SDAI ≤11 or CDAI ≤10) 1, 2
• Use validated composite measures (SDAI, CDAI, or DAS28) rather than individual parameters to guide treatment decisions 3

Monitoring Schedule

• Assess disease activity every 1-3 months during active disease 1, 2
• Expect >50% improvement within 3 months 2
• Target must be attained within 6 months 1, 2
• If these benchmarks are not met, escalate therapy immediately 1, 2

Treatment Escalation for Inadequate Response

When Methotrexate Monotherapy Fails

• For patients with poor prognostic factors (high rheumatoid factor, anti-CCP antibodies, erosive disease), add combination DMARD therapy 1, 2
• Triple therapy: Add sulfasalazine and hydroxychloroquine to methotrexate 1, 2
• This combination is more effective than methotrexate monotherapy, particularly in patients with poor prognostic factors 2

Biologic DMARD Escalation

• If moderate to high disease activity persists despite optimized conventional synthetic DMARDs, add a biologic DMARD or JAK inhibitor 1, 2
• First-line biologic options include TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab, golimumab) 1, 4
• Alternative biologics: IL-6 inhibitors (tocilizumab, sarilumab), T-cell costimulation modulator (abatacept), or anti-CD20 antibody (rituximab) 1
• JAK inhibitors (tofacitinib, baricitinib) are oral targeted synthetic DMARDs with efficacy comparable to biologics 1

Biomarker-Guided Selection

• Patients who are rheumatoid factor positive or anti-CCP positive may respond better to rituximab 1
• Seronegative patients may respond better to abatacept or tocilizumab 1
• IL-6 inhibitors (tocilizumab, sarilumab) are effective as monotherapy if methotrexate cannot be continued 1

When First Biologic Fails

• Switching to a different TNF inhibitor may be effective in 50-70% of cases 1
• Switching to a non-TNF biologic with a different mechanism of action is also appropriate 1
• Allow 3-6 months to fully assess efficacy of any new treatment before switching 2

Special Considerations Before Starting Biologics

Mandatory Screening

• Screen for tuberculosis (TST or IGRA) before initiating any biologic therapy 1, 4
• Screen for hepatitis B and C 1, 4
• Do not use biologics in untreated chronic hepatitis B 1
• Patients with history of lymphoproliferative malignancy, recent solid malignancy (within 5 years), or melanoma require special consideration 1, 4

Contraindications and Cautions

• Avoid TNF inhibitors in patients with heart failure (NYHA Class III/IV) 1
• Exercise caution in patients with previous serious infections, nontuberculous mycobacterial lung disease, or recurrent infections 1, 4
• Discontinue biologic therapy if serious infection or sepsis develops 4

Treatment De-escalation in Sustained Remission

• For patients in sustained remission (typically 6-12 months), consider cautious de-escalation of therapy 1, 2
• Approximately 15-25% of patients may achieve sustained drug-free remission 1, 2
• Predictors of successful drug-free remission include: shorter symptom duration before treatment, absence of rheumatoid factor or anti-CCP antibodies, lower disease activity before remission, and less baseline disability 3

Critical Pitfalls to Avoid

• Delaying DMARD initiation leads to irreversible joint damage and worse long-term outcomes 3, 1, 2
• Undertreating with suboptimal methotrexate doses (<20-25 mg weekly) prevents achieving treatment targets 1, 2
• Not escalating therapy when <50% improvement at 3 months or target not reached at 6 months 1, 2
• Using NSAIDs or corticosteroids alone provides only symptomatic relief without disease modification 2, 5
• Long-term glucocorticoid use without appropriate monitoring for adverse effects (osteoporosis, cardiovascular disease, cataracts) 3, 1, 2
• Overlooking comorbidities that influence treatment selection (tuberculosis, hepatitis, heart failure, previous malignancy) 1, 4
• Inadequate duration of treatment trial before concluding treatment failure (allow at least 3 months for methotrexate, 3-6 months for biologics) 3, 2