What is the treatment for a patient with Rheumatoid Arthritis (RA)?

Treatment of Rheumatoid Arthritis

Start methotrexate 15-25 mg weekly immediately upon diagnosis, combined with short-term low-dose glucocorticoids (≤10 mg/day prednisone equivalent for <3 months), and escalate to biologic DMARDs if remission or low disease activity is not achieved within 3-6 months. 1, 2

Initial Treatment Strategy

First-Line Therapy

• Methotrexate is the anchor DMARD and should be initiated at 15 mg weekly, rapidly escalating to 20-25 mg weekly within a few weeks as tolerated 1, 2
• Add folic acid supplementation to reduce methotrexate toxicity 2
• Combine with short-term glucocorticoids (≤10 mg/day prednisone or equivalent) for rapid symptom control while waiting for methotrexate to take effect, but limit duration to less than 3 months 1, 2
• After 1-2 years, long-term corticosteroid risks (cataracts, osteoporosis, fractures, cardiovascular disease) outweigh benefits 1, 2

Alternative First-Line DMARDs (if methotrexate contraindicated)

• Leflunomide, sulfasalazine, or hydroxychloroquine can be used as alternatives 1, 3

Treatment Targets and Monitoring

Disease Activity Goals

• Primary target: Clinical remission (SDAI ≤3.3 or CDAI ≤2.8) 1, 2, 4
• Acceptable alternative: Low disease activity (SDAI ≤11 or CDAI ≤10) 1, 2, 4

Monitoring Schedule

• Assess disease activity every 1-3 months during active disease 1, 2
• Expect >50% improvement within 3 months of starting treatment 2
• Target must be attained within 6 months or therapy must be changed 1, 2

Escalation Strategy for Inadequate Response

At 3 Months: If Inadequate Response to Methotrexate Monotherapy

Option 1: Optimize Methotrexate

• Increase dose to 25-30 mg weekly (maximum tolerated dose) 1, 2
• Switch to subcutaneous administration if oral dosing is inadequate, as SC methotrexate has improved bioavailability at higher doses 1, 4, 5

Option 2: Add Conventional DMARDs (Triple Therapy)

• Add hydroxychloroquine + sulfasalazine to methotrexate for triple-DMARD therapy 1, 4
• This is particularly appropriate for patients with moderate disease activity (SDAI >11 to ≤26) 1

Option 3: Add Biologic DMARD

• For patients with poor prognostic factors (high rheumatoid factor, anti-CCP antibodies, erosive disease, high disease activity), add a biologic agent 1, 2
• TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab, golimumab) are first-line biologic options 1, 6, 7
• TNF inhibitors should be combined with methotrexate when possible due to superior efficacy over monotherapy 1
• Infliximab must be used in combination with methotrexate, not as monotherapy 1

At 6 Months: If Target Not Reached

For patients on DMARD monotherapy or combination therapy:

• Switch to or add a biologic DMARD (TNF inhibitor, abatacept, or rituximab) 1

For patients already on a TNF inhibitor:

• Switch to an alternative biologic with a different mechanism of action rather than cycling within the same class 1, 4
• Options include: another TNF inhibitor (≤2 trials), abatacept (CTLA4:Ig), tocilizumab (anti-IL-6 receptor), or rituximab (anti-CD20) 1, 4
• Rituximab is particularly effective in seropositive patients (rheumatoid factor positive) 1, 4
• For seronegative patients with inadequate TNF inhibitor response, prefer abatacept or tocilizumab over rituximab 1

Beyond the First Year

For persistent moderate-to-high disease activity:

• Discontinue current biologic and start triple-DMARD therapy (methotrexate + hydroxychloroquine + sulfasalazine), OR 1
• Switch to alternative biologic agent with different mechanism of action 1, 4
• Allow 3-6 months to fully assess efficacy of any new treatment before making further changes 1, 2

Special Considerations

Concomitant Medications

• NSAIDs, salicylates, and analgesics may be continued during DMARD therapy for symptomatic relief 6, 8
• Gold salts and corticosteroids can be used safely with methotrexate 8
• Avoid combining with other biologic DMARDs (anakinra, abatacept) or other TNF blockers due to increased infection risk without added benefit 7

Remission and De-escalation

• Once remission is achieved, taper and discontinue prednisone 1, 2
• After sustained remission ≥1 year, consider de-escalation of therapy (≤1 trial) 1
• 15-25% of patients can achieve sustained drug-free remission 2
• If tapering biologics, do so cautiously and preferably when combined with a conventional DMARD 1

Critical Pitfalls to Avoid

Delayed Treatment

• Delaying DMARD initiation leads to irreversible joint damage 2, 9, 10
• Treatment must begin immediately upon diagnosis 1, 2

Suboptimal Dosing

• Undertreating with methotrexate doses <20-25 mg weekly prevents achieving treatment targets 2
• Failure to switch to subcutaneous methotrexate when oral dosing is inadequate 1, 4, 5

Inadequate Monitoring and Escalation

• Not escalating therapy when <50% improvement at 3 months or target not reached at 6 months 2
• Continuing ineffective therapy for more than 6 months before changing to an alternative mechanism 4

Inappropriate Medication Use

• Using NSAIDs or corticosteroids alone without DMARDs provides only symptomatic relief without disease modification 2
• High-dose corticosteroids alone do not prevent radiographic progression 2
• Prolonged corticosteroid use beyond 1-2 years without clear benefit 1, 2, 4

Poor Prognostic Factor Recognition

• Undertreating patients with erosive disease, high rheumatoid factor levels, or high disease activity who require aggressive combination therapy from the start 2

Adjunctive Management

Non-Pharmacologic Interventions

• Hand therapy exercises for patients with hand involvement 3
• Joint protection techniques and splinting/orthoses for affected joints 3
• Structured exercise program through physical therapy 2
• Occupational therapy for work modifications if needed 2

Bone Protection

• Calcium 500-1000 mg daily and vitamin D 800-1000 IU daily for patients on prolonged corticosteroids 2
• Consider bisphosphonate if DEXA shows osteoporosis 2

Pre-Treatment Screening

• Test for latent tuberculosis before initiating biologics and periodically during therapy 6, 7
• Complete age-appropriate vaccinations prior to starting biologics 6
• Avoid live vaccines during biologic therapy 7
• Screen for hepatitis B, hepatitis C, and assess for comorbidities 2, 9