What is the management of rheumatoid arthritis?

Management of Rheumatoid Arthritis

Immediate Actions Upon Suspicion

Refer urgently to a rheumatologist any patient with suspected persistent synovitis, even if rheumatoid factor is negative or acute-phase reactants are normal, particularly when small joints of hands/feet are affected, multiple joints are involved, or symptoms have persisted ≥3 months. 1, 2, 3

Diagnostic Testing

• Test for rheumatoid factor in all patients with suspected RA who have synovitis 1, 2
• Measure anti-cyclic citrullinated peptide (anti-CCP) antibodies if rheumatoid factor is negative and combination therapy is being considered 1, 2, 3
• Obtain baseline laboratory monitoring including CBC, liver enzymes, creatinine, and hepatitis B/C screening before starting treatment 3

First-Line Treatment Strategy

Start methotrexate 15 mg weekly with folic acid 1 mg daily immediately upon diagnosis as the cornerstone of initial therapy. 2, 3, 4

Methotrexate Optimization

• Escalate methotrexate dose to 20-25 mg weekly or maximal tolerated dose if inadequate response after 3 months 2, 3
• Switch to subcutaneous administration if oral route shows inadequate response 3
• Continue concomitant NSAIDs, low-dose glucocorticoids, or analgesics as needed 1, 4

Bridging Glucocorticoid Therapy

• Use short-term glucocorticoids (low to moderately high doses) as bridging therapy during DMARD initiation 2, 3
• Taper glucocorticoids as rapidly as clinically feasible once remission is achieved 2, 3
• Do not continue glucocorticoids beyond 1-2 years due to risks of cataracts, osteoporosis, fractures, and cardiovascular disease 3
• Consider intra-articular glucocorticoid injections for isolated joint inflammation 3

Treatment Goals and Monitoring

The primary goal is achieving clinical remission (SDAI ≤3.3 or CDAI ≤2.8) or low disease activity (SDAI ≤11 or CDAI ≤10). 2, 3

Monitoring Schedule

• Assess disease activity monthly for patients with high/moderate disease activity 2, 3
• Assess every 3-6 months for patients in low disease activity or remission 2, 3
• Adjust treatment at least every 3 months until target is reached 2, 3
• Allow at least 3-6 months to fully assess efficacy of any new treatment 3

Treatment Escalation Algorithm

Step 1: Methotrexate Monotherapy Failure (After 3-6 Months)

Add sulfasalazine and hydroxychloroquine to methotrexate to create triple-DMARD therapy before advancing to biologics. 3

• Triple-DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) is the next step for inadequate methotrexate response 3
• This combination should be tried for 3-6 months before declaring failure 3

Step 2: Triple-DMARD Therapy Failure

Switch to biologic agents, starting with TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, or infliximab) combined with methotrexate. 2, 3, 5

• TNF inhibitors should be combined with methotrexate for optimal efficacy 2
• Adalimumab dosing: 40 mg subcutaneously every other week 5
• Patients not taking concomitant methotrexate may benefit from increasing adalimumab to 40 mg weekly or 80 mg every other week 5

Step 3: First TNF Inhibitor Failure

Switch to an alternative mechanism of action rather than another TNF inhibitor when possible. 3

For Seropositive Patients (RF+ or ACPA+):

• Consider rituximab (anti-CD20), abatacept (CTLA4:Ig), or tocilizumab (anti-IL-6R) 2, 3
• Rheumatoid factor positive patients and those with anti-citrullinated protein antibodies respond favorably to rituximab 3

For Seronegative Patients:

• Preferentially use abatacept or tocilizumab rather than rituximab 3
• Seronegative patients with inadequate anti-TNF response show better outcomes with these agents 3

Step 4: Multiple Biologic Failures

• Consider alternative biologics with different mechanisms: abatacept, rituximab, tocilizumab, or anakinra 2, 3
• For refractory severe RA or when biologics are contraindicated, consider azathioprine, cyclosporine A, or in exceptional cases, cyclophosphamide 2

Alternative First-Line DMARDs

When methotrexate is contraindicated or not tolerated, use leflunomide, sulfasalazine, or injectable gold as alternative first-line DMARDs. 2

Remission and De-escalation Strategy

For patients achieving sustained remission ≥1 year, consider careful de-escalation of therapy, as 15-25% may achieve sustained drug-free remission. 3

Predictors of Successful Drug-Free Remission:

• Shorter symptom duration 3
• Absence of rheumatoid factor/ACPA 3
• Lower baseline disease activity 3
• Less baseline disability 3

De-escalation Approach:

• Consider tapering biologic DMARDs first in patients on combination therapy 2
• In cases of sustained long-term remission, cautiously reduce synthetic DMARD dosage 2
• Most patients experiencing flare-up after 3-6 months achieve remission again with treatment resumption without radiologic progression 3

Non-Pharmacological Management

Implement thermal modalities, joint protection techniques, activity pacing, regular aerobic and resistance exercise programs, appropriate splinting/orthoses, and assistive devices to address mechanical symptoms from structural joint damage. 2, 3

Distinguishing Inflammatory vs. Mechanical Symptoms

Inflammatory Symptoms (Respond to Anti-Inflammatory Therapy):

• Morning stiffness lasting ≥1 hour 6
• Symmetric polyarthritis with joint swelling 6
• Systemic manifestations (fatigue, low-grade fever) 6

Mechanical Symptoms (Require Physical Interventions):

• Joint instability and deformity 3, 6
• Limited range of motion not responsive to anti-inflammatory treatment 3, 6
• Pain with weight-bearing or specific movements rather than at rest 6
• These symptoms will not improve with anti-inflammatory therapy alone and require different management approaches 6

Multidisciplinary Team Components:

• Patient education about disease pathophysiology, self-management skills, and joint protection principles 2
• Occupational therapy for joint protection instruction and prescription of assistive devices, orthotics, and splints 2
• Dynamic exercise programs incorporating both aerobic exercise and progressive resistance training 2
• Involvement of rheumatologists, nurses, physical and occupational therapists, and psychologists 2

Critical Pitfalls to Avoid

Do not delay referral based on normal inflammatory markers or negative rheumatoid factor, as early aggressive treatment prevents irreversible joint damage. 3

• Do not use inadequate methotrexate doses; escalate to 20-25 mg weekly before declaring treatment failure 3
• Do not continue ineffective therapy beyond 3 months without escalation 3
• Do not fail to distinguish inflammatory from mechanical symptoms, as mechanical symptoms require different management approaches and won't respond to anti-inflammatory therapy alone 3, 6
• Do not overlook the importance of treat-to-target strategy with frequent monitoring and rapid treatment adjustments 3

Special Monitoring Considerations for Biologics

TNF Inhibitor Safety (Adalimumab Example):

• Screen for latent tuberculosis before initiating therapy and during treatment 5
• Initiate treatment for latent TB prior to starting TNF inhibitors 5
• Monitor closely for serious infections including invasive fungal infections (histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis) 5
• Consider empiric anti-fungal therapy in at-risk patients who develop severe systemic illness 5
• Be aware of increased risk of lymphoma and other malignancies, particularly hepatosplenic T-cell lymphoma in patients receiving concomitant azathioprine or 6-mercaptopurine 5
• Discontinue if patient develops serious infection or sepsis 5