What is the recommended treatment plan for rheumatoid arthritis?

Treatment of Rheumatoid Arthritis

Start methotrexate 15-25 mg weekly with folic acid supplementation immediately upon diagnosis, escalating rapidly to 25-30 mg weekly within a few weeks, combined with short-term low-dose glucocorticoids (≤10 mg/day prednisone equivalent) 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 patients with active RA and should be initiated at 15-25 mg weekly with folic acid supplementation 1, 2
• Rapidly escalate to the optimal dose of 25-30 mg weekly within a few weeks and maintain this maximal dose for at least 3 months before assessing efficacy 2
• If oral methotrexate is not tolerated or ineffective, switch to subcutaneous administration 2
• Therapy with DMARDs must be started as soon as the diagnosis of RA is made - delaying DMARD initiation leads to irreversible joint damage 1, 2

Glucocorticoid Bridge Therapy

• Add low-dose glucocorticoids (≤10 mg/day prednisone or equivalent) for rapid symptom relief while methotrexate takes effect 1, 2
• Use glucocorticoids at the lowest possible dose and for the shortest possible 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 2

Alternative First-Line DMARDs

• In patients with methotrexate contraindications or early intolerance, use leflunomide or sulfasalazine as part of the first treatment strategy 1

Treatment Targets and Monitoring

Primary Goals

• The primary treatment target is clinical remission, defined as SDAI ≤3.3 or CDAI ≤2.8, or ACR-EULAR Boolean criteria 1, 2
• Low disease activity (SDAI ≤11 or CDAI ≤10) is an acceptable alternative if remission cannot be achieved 1, 2

Monitoring Schedule

• Assess disease activity every 1-3 months during active disease 1
• Aim for >50% improvement within 3 months of initiating therapy 1, 2
• The treatment target must be attained within 6 months 1, 2
• If there is no improvement by 3 months or target not reached by 6 months, therapy must be adjusted 1

Treatment Escalation for Inadequate Response

Patients WITHOUT Poor Prognostic Factors

• Change to another conventional synthetic DMARD strategy 1
• Consider triple therapy with methotrexate + sulfasalazine + hydroxychloroquine 1, 2

Patients WITH Poor Prognostic Factors

Poor prognostic factors include: high rheumatoid factor or anti-CCP antibody levels (especially at high levels), high disease activity, early joint damage, or failure of 2 conventional synthetic DMARDs 1, 2

• Add a biologic DMARD or JAK inhibitor to methotrexate if inadequate response after 3-6 months 1, 2
• TNF inhibitors (infliximab, etanercept, adalimumab, certolizumab pegol, golimumab) are typically first-line biologic agents 1, 2
• Alternative biologics include IL-6 receptor antagonists (tocilizumab), T-cell costimulation modulators (abatacept), or rituximab under certain circumstances 1, 3
• JAK inhibitors (tofacitinib, baricitinib) may be considered 1
• Biologic therapy should be used in combination with methotrexate when possible due to superior efficacy of this combination over biologic monotherapy 1

After First Biologic Failure

• Switch to another biologic DMARD with a different mechanism of action 1, 2
• If a first TNF inhibitor has failed, patients may receive another TNF inhibitor or a biological agent with another mode of action 1
• Allow 3-6 months to fully assess efficacy of any new treatment 2

Special Considerations

Combination DMARD Therapy

• For patients with poor prognostic factors (erosive disease, high rheumatoid factor levels), combination therapy with methotrexate + hydroxychloroquine is more effective than methotrexate monotherapy 2
• Consider adding sulfasalazine for complete triple therapy 2

Safety Monitoring

• Screen for tuberculosis before starting biologic agents or JAK inhibitors 2, 3
• Administer age-appropriate vaccines (including Herpes Zoster vaccine) in patients taking DMARDs or biologics 2
• Obtain baseline complete blood count and liver function tests prior to treatment 3
• Do not initiate methotrexate or biologics in patients with ANC below 2000 per mm³, platelet count below 100,000 per mm³, or ALT/AST above 1.5 times ULN 3

De-escalation Strategy

• If sustained remission is achieved for ≥1 year, consider de-escalation of therapy 2
• Taper and discontinue prednisone first 2
• 15-25% of patients may achieve sustained drug-free remission 2
• In cases of sustained long-term remission, cautious reduction of the conventional synthetic DMARD dose could be considered 1

Critical Pitfalls to Avoid

• Never delay DMARD initiation - this leads to irreversible joint damage 2
• Never undertreat with suboptimal methotrexate doses (<25 mg weekly) - this prevents achieving treatment targets 2
• Never use NSAIDs or corticosteroids alone - these provide only symptomatic relief without disease modification 2
• Never fail to escalate therapy when <50% improvement at 3 months or target not reached at 6 months 2
• Never undertreate patients with poor prognostic factors (erosive disease, high rheumatoid factor levels) - these patients require aggressive combination therapy from the start 2
• Never use high-dose corticosteroids alone - they are not disease-modifying therapy and do not prevent radiographic progression 2