Initial Treatment for Rheumatoid Arthritis
Methotrexate should be started immediately as first-line therapy once RA is diagnosed, combined with short-term low-dose glucocorticoids as bridging therapy. 1, 2
First-Line Treatment Strategy
Start methotrexate as the anchor drug as soon as RA diagnosis is confirmed—do not delay treatment. 1, 2 The optimal dose is 25 mg weekly (oral or subcutaneous), combined with folic acid supplementation. 3, 4
Glucocorticoid Bridging Therapy
Add short-term low-dose glucocorticoids (≤10 mg/day prednisone equivalent) when initiating methotrexate to provide rapid symptom control while waiting for methotrexate to take effect. 1, 2 These should be tapered as rapidly as clinically feasible, ideally within 6 months. 1
Alternative First-Line Options (When Methotrexate is Contraindicated)
If methotrexate cannot be used due to contraindications or early intolerance:
- Leflunomide is the preferred alternative, with similar clinical efficacy and radiographic outcomes to methotrexate. 1, 5, 2
- Sulfasalazine is another acceptable option. 1, 5, 2
Treatment Target and Monitoring Strategy
Aim for remission or low disease activity as the treatment target in every patient using a treat-to-target approach. 1, 2, 4
Monitoring Schedule
- Assess disease activity every 1-3 months during active disease using tender/swollen joint counts, patient and physician global assessments, ESR, and CRP. 1, 2
- If no improvement by 3 months after starting treatment, therapy must be adjusted. 1, 2
- If treatment target not reached by 6 months, therapy must be escalated. 1, 2, 4
Treatment Escalation Algorithm
Without Poor Prognostic Factors
If methotrexate monotherapy fails and poor prognostic factors are absent:
- Switch to or add another conventional synthetic DMARD (such as sulfasalazine or hydroxychloroquine). 1, 2
- The most common combination is methotrexate + sulfasalazine + hydroxychloroquine (triple therapy). 2
With Poor Prognostic Factors Present
If poor prognostic factors exist (high disease activity, positive rheumatoid factor/anti-CCP, early erosions):
- Add a biologic DMARD or JAK inhibitor to methotrexate. 1, 2
- Options include TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), IL-6 inhibitors (tocilizumab, sarilumab), abatacept, or JAK inhibitors. 1, 2
- Biologic DMARDs should be combined with methotrexate whenever possible, as combination therapy shows superior efficacy over biologic monotherapy. 2, 6
Evidence Supporting Early Intensive Treatment
The 2007 EULAR guidelines demonstrated that initial intensive treatment provides better clinical and radiographic outcomes than DMARD monotherapy, particularly in patients with severe disease. 1 Studies including TICORA, PREMIER, and ASPIRE showed that achieving remission or low disease activity is associated with arrest of radiographic progression and better physical function. 1
More recent 2019 EULAR recommendations (highest quality evidence) confirm methotrexate as first-line therapy with level 1a evidence and strength A recommendation. 1
Critical Pitfalls to Avoid
- Delayed treatment escalation is the most common error—do not wait beyond 3 months without improvement or 6 months without reaching target before adjusting therapy. 2, 3
- Inadequate methotrexate dosing—ensure patients receive optimal doses (up to 25 mg weekly) before declaring treatment failure. 3, 4
- Failure to use glucocorticoid bridging—this provides rapid symptom control and may improve long-term radiographic outcomes. 1, 2
- Not screening for infections before starting biologic therapy, particularly tuberculosis and hepatitis B. 6