How should a flare of rheumatoid arthritis be managed in an adult already on disease‑modifying antirheumatic therapy?

Management of Rheumatoid Arthritis Flare in Patients Already on DMARD Therapy

When a patient on disease-modifying antirheumatic therapy experiences a flare, immediately optimize the current DMARD regimen by escalating methotrexate to 25–30 mg weekly (oral or subcutaneous), add short-term low-dose glucocorticoids (≤10 mg/day prednisone-equivalent for <3 months), and if inadequate response persists after 3 months or target is not reached by 6 months, add a biologic DMARD or JAK inhibitor. 1

Immediate Assessment and Optimization

Verify Current DMARD Adequacy

• Confirm that methotrexate dose is optimized at 20–25 mg weekly before declaring treatment failure; most patients are undertreated with suboptimal doses. 2
• If oral methotrexate at 20–25 mg weekly is ineffective or poorly tolerated, switch to subcutaneous administration before escalating to biologic therapy, as bioavailability improves significantly. 2, 3
• Maintain the maximal tolerated methotrexate dose for at least 3 months to fully assess efficacy before making further therapeutic changes. 2

Add Glucocorticoid Bridge Therapy

• Initiate low-dose prednisone ≤10 mg/day (or equivalent) immediately to provide rapid symptom control while optimizing DMARD therapy. 1, 2
• Limit glucocorticoid duration to less than 3 months and use the lowest effective dose, as prolonged use beyond 1–2 years causes cumulative toxicity including osteoporosis, fractures, cataracts, and cardiovascular disease that outweighs benefits. 1, 2
• Taper and discontinue prednisone as soon as disease control is achieved with DMARD optimization or escalation. 1

Define Treatment Targets and Timeline

Establish Remission Goals

• The primary therapeutic target is ACR-EULAR remission: SDAI ≤3.3, CDAI ≤2.8, or Boolean criteria (tender joint count ≤1, swollen joint count ≤1, CRP ≤1 mg/dL, patient global assessment ≤1 on 0–10 scale). 1, 2
• If remission is unattainable, low disease activity is an acceptable alternative: SDAI ≤11 or CDAI ≤10. 1
• Persistent ACR-EULAR remission is associated with the lowest risk of flares, while tapering in low disease activity (including less stringent remission states) carries higher flare risk and is not recommended. 1

Monitor Disease Activity Rigorously

• Assess disease activity every 1–3 months during active disease using validated composite measures (DAS28, SDAI, or CDAI). 1, 2
• Expect ≥50% improvement in disease activity within the first 3 months of any therapeutic intervention. 1, 2
• The treatment target must be reached within 6 months; failure to achieve this mandates escalation. 1, 2

Escalation Strategy for Inadequate Response

Patients Without Poor Prognostic Factors

• Add conventional synthetic DMARDs in combination (triple therapy: methotrexate + sulfasalazine + hydroxychloroquine) if biologic therapy is not immediately indicated. 1, 2
• Under tight control conditions, combination csDMARD therapy achieves comparable outcomes to immediate biologic escalation in patients lacking poor prognostic markers. 1

Patients With Poor Prognostic Factors

• Poor prognostic factors include: high rheumatoid factor or anti-CCP titers, high baseline disease activity, early erosive changes on imaging, or failure of two csDMARDs. 2
• Add a biologic DMARD or JAK inhibitor to methotrexate when inadequate response persists after 3–6 months of optimized csDMARD therapy. 1, 2
• TNF-α inhibitors (adalimumab, etanercept, infliximab, certolizumab pegol, golimumab) are preferred first-line biologic agents for most patients. 1, 2, 3
• Alternative biologic classes include: IL-6 receptor antagonists (tocilizumab), T-cell costimulation modulators (abatacept), and rituximab in selected cases. 1, 2
• JAK inhibitors (tofacitinib, baricitinib) are acceptable options when biologics are unsuitable or after biologic failure, with proven efficacy superior to placebo and comparable to methotrexate. 1
• Biologic agents should be combined with methotrexate whenever possible, as combination therapy demonstrates superior efficacy compared with biologic monotherapy. 2, 3

After First Biologic Failure

• Switch to a biologic with a different mechanism of action if the initial biologic (including a TNF inhibitor) fails, as registry data and observational studies suggest better efficacy than using a second agent from the same class. 1
• After failure of a first TNF inhibitor, either another TNF inhibitor or a different biologic class may be employed, though switching mechanism of action is now preferred based on recent evidence. 1
• Allow 3–6 months to fully assess the efficacy of any newly introduced biologic or targeted synthetic DMARD before making further changes. 1, 2

Critical Pitfalls to Avoid

Undertreatment Errors

• Do not continue suboptimal methotrexate doses (<20–25 mg weekly) when disease activity persists, as this prevents achieving treatment targets and allows progressive joint damage. 2
• Do not delay DMARD escalation when there is <50% improvement at 3 months or target not reached at 6 months, as small increases in joint damage accumulate over years and lead to irreversible disability. 1, 2
• Do not rely on NSAIDs or corticosteroids alone for flare management, as they provide only symptomatic relief without disease modification and permit unchecked joint destruction. 2, 4

Glucocorticoid Misuse

• Do not continue systemic corticosteroids beyond 1–2 years, as cumulative adverse effects (fractures, cataracts, cardiovascular disease, osteoporosis) outweigh any symptomatic benefit. 1, 2
• Do not use high-dose corticosteroids as sole therapy, as they do not halt radiographic progression despite providing symptom relief. 1, 2

Monitoring Failures

• Do not taper therapy in low disease activity states (including less stringent remission definitions), as this carries higher risk of flares compared with persistent ACR-EULAR remission. 1
• Flares after biologic DMARD tapering are associated with progression of joint damage, especially when leading to long-term increase in disease activity, though short-lived flares may not cause radiographic progression. 1