What are the steps to manage a rheumatoid arthritis (RA) flare-up?

Managing Rheumatoid Arthritis Flare-Ups

Immediately initiate low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for rapid symptom control while simultaneously escalating your DMARD therapy. 1

Immediate Flare Control

Administer glucocorticoids through the most appropriate route:

• Oral prednisone ≤10 mg/day for generalized polyarticular flares 2, 1
• Intramuscular injection for patients with adherence concerns or gastrointestinal intolerance 1
• Intra-articular injection when only 1-2 joints are predominantly involved 1

Critical timing: Taper glucocorticoids as rapidly as clinically feasible once disease control is achieved, ideally within 3 months. 2, 1 Never continue glucocorticoids beyond 3 months at doses >10 mg/day due to cumulative toxicity including osteoporosis, cardiovascular disease, and cataracts. 1

Assess Current Disease Activity and Treatment Adequacy

Measure disease activity immediately using validated composite measures:

• SDAI (Simplified Disease Activity Index) or CDAI (Clinical Disease Activity Index) are preferred 1, 3
• DAS28-CRP is acceptable but less stringent 2, 1

Define your treatment target:

• Primary goal: Clinical remission (SDAI ≤3.3 or CDAI ≤2.8) 1, 3
• Acceptable alternative: Low disease activity (SDAI ≤11 or CDAI ≤10) for patients with long-standing disease 1, 3

Optimize or Escalate DMARD Therapy

If Patient Is on Methotrexate Monotherapy:

First, ensure methotrexate is truly optimized:

• Increase to 20-25 mg weekly (oral or subcutaneous) if not already at this dose 1, 3
• Switch to subcutaneous administration if oral dosing at maximum tolerated dose proves inadequate 3

If methotrexate is already optimized, add combination therapy:

• Add triple conventional synthetic DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) as an evidence-based alternative before advancing to biologics 1, 3
• OR proceed directly to biologic therapy if poor prognostic factors are present (positive RF/anti-CCP, very high disease activity, early joint damage, or failure of ≥2 conventional DMARDs) 1

If Patient Is Already on Combination Conventional Synthetic DMARDs:

Proceed directly to biologic therapy rather than adjusting conventional DMARDs further. 1

First-line biologic options:

• TNF inhibitor + methotrexate (adalimumab, certolizumab, etanercept, golimumab, or infliximab) - TNF inhibitors have superior efficacy when combined with methotrexate compared to monotherapy 1, 4
• IL-6 inhibitor (tocilizumab or sarilumab) - may be preferred if methotrexate cannot be used as comedication 1

If First Biologic Has Failed:

Switch to a biologic with a different mechanism of action rather than cycling within the same class:

• After TNF inhibitor failure: Switch to abatacept, rituximab, or tocilizumab 2, 1, 3
• After non-TNF biologic failure: Consider TNF inhibitor if patient is TNF-naive 2

Note: Switching to a non-TNF biologic may provide better outcomes than switching to a second TNF inhibitor, though either approach is acceptable. 1 Expected response rate to a second TNF inhibitor is 50-70%. 1

Monitoring Schedule During Active Flare

Reassess disease activity every 1-3 months during active disease using the same validated measure (SDAI, CDAI, or DAS28). 1, 3

Treatment adjustment timeline:

• If no improvement by 3 months: Adjust therapy immediately 1, 3
• If treatment target not reached by 6 months: Escalate therapy 1, 3

Critical pitfall to avoid: Do not continue ineffective therapy beyond 3 months hoping for delayed response—this allows irreversible joint damage to progress. 1, 3

Laboratory Monitoring When Escalating DMARDs

For methotrexate, leflunomide, or sulfasalazine:

• First 3 months: Check CBC, liver transaminases, and creatinine every 2-4 weeks 2
• 3-6 months: Every 8-12 weeks 2
• Beyond 6 months: Every 12 weeks 2

More frequent monitoring is required if abnormal laboratory results develop, multiple therapies are used, or comorbidities are present. 2

Special Considerations

For RF-positive patients: Rituximab is particularly effective and should be strongly considered if TNF inhibitors fail. 3, 4

Flares after biologic tapering are associated with progression of joint damage, especially when leading to long-term increase in disease activity. 2 Therefore, do not attempt tapering during an active flare—first achieve sustained remission. 2

Sustained remission (not just low disease activity) is required before considering any treatment de-escalation, as low disease activity carries higher risk of flares. 2