What laboratory tests and treatments are used for rheumatoid arthritis (RA) diagnosis and management?

Rheumatoid Arthritis Laboratory Testing

Essential Diagnostic Laboratory Tests

For initial diagnosis of rheumatoid arthritis, order rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA/anti-CCP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count with differential, comprehensive metabolic panel including liver and renal function, and urinalysis. 1

Serologic Testing

• Anti-CCP antibodies have the highest specificity (90%) with moderate sensitivity (60%) for RA diagnosis and should be ordered in all suspected cases 1, 2
• Rheumatoid factor (RF) has lower specificity (70%) but similar sensitivity to anti-CCP and remains an important diagnostic marker 1, 2
• In the 2010 ACR/EULAR classification criteria, serology is scored as: negative RF and ACPA = 0 points, low positive RF or ACPA = 2 points, high positive RF or ACPA = 3 points 1
• Seronegative RA accounts for 20-30% of cases, so negative RF does not exclude the diagnosis 1
• Combined detection of RF and anti-CCP increases diagnostic accuracy to 88.5% 2

Inflammatory Markers

• CRP is preferred over ESR because it is more reliable, not age-dependent, and provides a simple, validated, reproducible test 1, 3
• In the classification criteria, abnormal CRP or ESR = 1 point, normal = 0 points 1
• Critical pitfall: Approximately 40-50% of patients with active RA can have normal acute phase reactants—do not dismiss the diagnosis based solely on normal ESR/CRP 1, 4
• ESR and CRP should be measured at baseline for diagnostic and prognostic purposes 1

Baseline Laboratory Assessment

• Complete blood count with differential to assess for cytopenias before starting treatment and calculate neutrophil-to-lymphocyte ratio 1, 3
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and uric acid levels 1, 3
• Urinalysis as part of standard initial workup 1, 3
• Antinuclear antibodies (ANA) if diagnosis is uncertain to screen for other connective tissue diseases 1
• HLA-B27 only if spondyloarthropathy is being considered based on clinical features 1

Pre-Treatment Screening

Mandatory Infectious Disease Screening Before Biologics

• Tuberculosis screening with tuberculin skin test or interferon-gamma release assay (IGRA preferred over TST in patients with prior BCG vaccination) regardless of risk factors 3, 5
• Hepatitis B surface antigen, surface antibody, and core antibody 3, 5
• Hepatitis C antibody 3, 5
• Annual TB testing is required for patients on biologics who live, travel, or work where TB exposure is likely 3

Pregnancy Considerations

• Pregnancy testing should be considered before starting teratogenic medications such as methotrexate or leflunomide, with mandatory counseling on effective contraception 3

Disease Activity Monitoring

Composite Disease Activity Measures

The ACR recommends 6 validated measures for point-of-care RA disease activity measurement: CDAI, DAS28 (ESR or CRP), PAS, PAS-II, RAPID-3, and SDAI. 6

• DAS28 (Disease Activity Score with 28-joint counts) incorporates ESR or CRP, tender joint count, swollen joint count, and patient global assessment 1, 7

  • Remission: <2.6
  • Low disease activity: ≥2.6 to <3.2
  • Moderate disease activity: ≥3.2 to ≤5.1
  • High disease activity: >5.1 1

• SDAI (Simplified Disease Activity Index) combines clinical assessment and CRP 1, 7

  • Remission: ≤3.3
  • Low disease activity: ≤11
  • Moderate: ≤26
  • High: >26 1

• CDAI (Clinical Disease Activity Index) does not require laboratory tests and relies purely on clinical assessment 1, 7

  • Remission: ≤2.8
  • Low disease activity: ≤10
  • Moderate: ≤22
  • High: >22 1

Frequency of Laboratory Monitoring

• CRP should be repeated at each visit to monitor disease activity 1, 3
• Disease activity should be assessed every 1-3 months during active disease with therapeutic adaptation to reach remission or low disease activity within 3-6 months 3
• Regular follow-up using composite disease activity measures guides treat-to-target strategies 3

Medication Monitoring

DMARD Monitoring Schedule

• For patients on methotrexate, leflunomide, or sulfasalazine: CBC, liver transaminases, and serum creatinine every 2-4 weeks during first 3 months or after dose increases 3
• After initial period: every 8-12 weeks between 3-6 months of stable therapy, then every 12 weeks after 6 months 3
• Patients with comorbidities, abnormal labs, or multiple therapies require more frequent testing 3

Other Medication Monitoring

• Hydroxychloroquine: no routine laboratory monitoring required after baseline labs 3
• NSAIDs: CBC, liver function tests, and renal function tests every 6-12 months 3
• Tocilizumab or tofacitinib: lipid profiles at baseline and monitored periodically 3

Treatment Target and Follow-up

The primary treatment target is remission, defined as absence of signs or symptoms of inflammatory disease activity, or at minimum low disease activity, which should be attained within 6 months. 1, 8

• Measure composite disease activity using SDAI or CDAI at initial visit and every 4-6 weeks during active treatment 1
• If inadequate response after 3 months of methotrexate, consider triple DMARD therapy or adding a biologic agent such as a TNF inhibitor 1
• Baseline imaging with bilateral hand, wrist, and foot X-rays is essential for monitoring structural damage progression 1
• Repeat imaging at 6 months and 12 months to monitor radiographic progression 1