What are the recommended tests and treatments for diagnosing and managing rheumatoid arthritis?

Rheumatoid Arthritis Testing

Test for rheumatoid factor (RF) in all patients with suspected rheumatoid arthritis who present with synovitis, and add anti-cyclic citrullinated peptide (anti-CCP) antibody testing if RF is negative or when considering combination therapy. 1

Diagnostic Laboratory Testing Algorithm

Initial Serologic Testing

• Rheumatoid Factor (RF): Offer RF testing to all patients with suspected RA who have synovitis, recognizing that 30-40% of RA patients may be RF-negative 1, 2
• Anti-CCP Antibodies: Measure anti-CCP in RF-negative patients and when combination therapy is being considered 1
• Anti-CCP has higher specificity (90%) for RA than RF and provides important prognostic information 3
• High-positive RF or anti-CCP (>3 times upper limit of normal) carries more diagnostic weight than low-positive results in classification criteria 3

Inflammatory Markers at Baseline

• ESR and CRP: Obtain at baseline for both diagnostic and prognostic purposes 3
• These acute-phase reactants help assess disease activity and guide treatment decisions 3

Baseline Assessment Panel

• Complete blood count with differential and platelet counts 4
• Hepatic enzymes 4
• Renal function tests 4
• Chest X-ray 4

Imaging Studies

Plain Radiography

• Obtain X-rays of hands, wrists, and feet at baseline to predict development of RA and disease persistence 3
• Repeat X-rays within 1 year if disease persists 3
• Early radiographic features include soft tissue swelling and juxtaarticular osteoporosis 5

Advanced Imaging When Indicated

• Ultrasound or MRI may detect subclinical inflammation when clinical examination is inconclusive 3
• Ultrasonography can show synovial thickening even within finger joints in early disease 5

Critical Referral Criteria

Refer urgently for specialist evaluation even with normal acute-phase response or negative RF if: 1, 2

• Small joints of hands or feet are affected
• More than one joint is affected
• Delay of 3 months or longer between symptom onset and seeking medical advice

Common Pitfall to Avoid

Do not delay referral based on negative RF or normal inflammatory markers—seronegative RA exists in 30-40% of patients and early specialist evaluation is crucial for preventing irreversible joint damage 2, 6

Prognostic Value of Testing

• Dual positivity (RF + anti-CCP) and high antibody levels are associated with higher risk of persistent and erosive disease 2
• Anti-CCP antibodies provide significant prognostic information beyond diagnosis 3
• CRP levels correlate with clinical assessment and radiographic changes 5

Monitoring During Treatment

Frequency of Laboratory Monitoring

• Hematology: at least monthly 4
• Renal and liver function: every 1-2 months 4
• More frequent monitoring during initial therapy, dose changes, or periods of increased risk (e.g., dehydration) 4

Disease Activity Measures

• Monitor with composite disease activity measures (DAS28, SDAI, or CDAI) every 4-6 weeks after treatment initiation 3
• Target is remission or low disease activity within 6 months 1, 3, 6

Treatment Approach Based on Testing

First-Line Therapy

• Methotrexate is first-line therapy at optimal dose of 25 mg weekly in combination with glucocorticoids 6
• 40-50% of patients reach remission or low disease activity with this regimen 6

Escalation Strategy

• If methotrexate fails, add biologic agents (TNF inhibitors) or Janus kinase inhibitors in combination with methotrexate 6
• Sequential application of targeted therapies allows up to 75% of patients to reach treatment target over time 6
• Rituximab may be particularly effective in seropositive patients (RF+ and anti-CCP+) 3

Hepatotoxicity Monitoring

• Liver function tests at baseline and every 4-8 weeks during methotrexate therapy 4
• Pretreatment liver biopsy for patients with excessive alcohol consumption, persistently abnormal baseline liver tests, or chronic hepatitis B or C 4
• Persistent liver function abnormalities may precede fibrosis or cirrhosis in RA patients 4