What is the recommended management approach for rheumatoid arthritis?

Rheumatoid Arthritis Management

Start methotrexate 15-25 mg weekly plus short-term glucocorticoids immediately upon diagnosis, aiming for remission or low disease activity within 6 months, and escalate to biologic DMARDs if this fails in patients with poor prognostic factors. 1

Initial Treatment Strategy

First-Line Therapy

• Initiate methotrexate as the anchor drug at 15-25 mg weekly (oral or subcutaneous) with folic acid supplementation 1, 2
• Rapidly escalate to the optimal dose of 25-30 mg weekly within a few weeks, maintaining this maximal dose for at least 3 months 1
• Add short-term glucocorticoids (≤10 mg/day prednisone equivalent) for rapid symptom control, using the lowest dose for the shortest duration (less than 3 months) 1, 2
• Maximum efficacy of methotrexate may not be seen until 4-6 months in many patients 1

Route of Administration

• Start with oral methotrexate, but switch to subcutaneous administration if there is inadequate response, poor compliance, or gastrointestinal side effects 3
• Subcutaneous administration may improve bioavailability in patients not responding to oral therapy 1

Alternative First-Line Agents (if MTX contraindicated)

• Leflunomide 20 mg daily or sulfasalazine 3-4 g/day (enteric coated) should be used if methotrexate is contraindicated due to hepatic/renal disease or early intolerance 1
• Sulfasalazine is considered safe during pregnancy 1

Treatment Targets and Monitoring

Target Goals

• Primary target: Clinical remission (SDAI ≤3.3 or CDAI ≤2.8, or ACR-EULAR Boolean criteria) 1, 2
• Acceptable alternative: Low disease activity (SDAI ≤11 or CDAI ≤10) 1

Monitoring Schedule

• Assess disease activity every 1-3 months during active disease 2, 4
• Aim for >50% improvement within 3 months 1
• Target must be attained within 6 months 1
• Monitor every 4-8 weeks in the first year, then every 8-12 weeks once stable 2

Mandatory Baseline Investigations

• Complete blood count with differential 2, 3
• Hepatic function tests (transaminases) 2, 3
• Renal function (creatinine with creatinine clearance calculation) 2, 3
• Chest radiograph 3
• Hepatitis B and C serologies 3
• Rheumatoid factor and anti-CCP antibodies 1, 2

Ongoing Monitoring

• Full blood count, serum transaminases, and creatinine at least monthly for first 3 months, then every 4-12 weeks 3

Escalation Strategy for Inadequate Response

Risk Stratification at 3-6 Months

Without poor prognostic factors:

• Switch to or add another conventional synthetic DMARD (leflunomide or sulfasalazine) plus short-term glucocorticoids 1
• Consider triple DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) 1, 2

With poor prognostic factors (high RF/ACPA, high disease activity, early erosions, failure of 2 csDMARDs):

• Add a biologic DMARD or JAK inhibitor to methotrexate 1, 2
• Options include TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), abatacept, tocilizumab, rituximab, or JAK inhibitors (tofacitinib, baricitinib) 1

If First Biologic Fails

• Switch to another biologic DMARD with a different mechanism of action 1
• After inadequate response to TNF inhibitors: consider abatacept, tocilizumab, or rituximab 1
• For seronegative patients (RF and ACPA negative) with inadequate anti-TNF response: prefer abatacept or tocilizumab over rituximab 1
• Allow 3-6 months to fully assess efficacy of any new treatment 1

Special Considerations

Combination Therapy Rationale

• Patients with erosive disease and high rheumatoid factor require aggressive combination therapy from the start 2
• Combination of methotrexate and hydroxychloroquine is more effective than methotrexate monotherapy in patients with poor prognostic factors 2

Glucocorticoid Management

• Taper and discontinue prednisone once remission is achieved 1
• After 1-2 years, long-term corticosteroid risks (cataracts, osteoporosis, fractures, cardiovascular disease) outweigh benefits 1, 2
• For prolonged high-dose steroid use: add calcium 500-1000 mg daily, vitamin D 800-1000 IU daily, and consider bisphosphonate if DEXA shows osteoporosis 2

De-escalation in Sustained Remission

• If sustained remission ≥1 year, consider tapering biologic DMARDs 1
• 15-25% of patients may achieve sustained drug-free remission, particularly those with shorter symptom duration, absence of RF/ACPA, and lower baseline disease activity 1
• Most patients who flare after tapering achieve remission again with treatment resumption without radiologic progression 1

Critical Pitfalls to Avoid

Delayed Treatment

• Delaying DMARD initiation leads to irreversible joint damage 2, 5
• Refer urgently to rheumatology if small joints of hands/feet affected, multiple joints involved, or >3 months symptom duration, even with negative RF and normal acute phase reactants 1

Inadequate Dosing

• Undertreating with suboptimal methotrexate doses (<25 mg weekly) prevents achieving treatment targets 1, 3
• Failing to maintain maximal tolerated methotrexate dose for at least 3 months before declaring treatment failure 1

Symptomatic Treatment Only

• NSAIDs or corticosteroids alone provide only symptomatic relief without disease modification 2
• High-dose corticosteroids alone do not prevent radiographic progression 2

Inadequate Escalation

• Not escalating therapy when <50% improvement at 3 months or target not reached at 6 months 1, 4
• Patients with erosive disease and high RF levels require combination therapy, not monotherapy 2

Monitoring Failures

• Not performing mandatory baseline investigations before starting DMARDs, particularly hepatitis serologies and chest radiograph 3
• Inadequate frequency of blood monitoring (must be at least monthly for first 3 months) 3