What is the best strategy for managing a rheumatoid arthritis (RA) flare in a patient already on a disease-modifying antirheumatic drug (DMARD)?

Managing Rheumatoid Arthritis Flares in Patients Already on DMARDs

For a patient experiencing an RA flare while already on a DMARD, add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) as immediate bridging therapy while simultaneously escalating DMARD therapy based on disease activity assessment and prognostic factors. 1, 2

Immediate Flare Management Strategy

Step 1: Add Bridging Glucocorticoid Therapy

• Initiate low-dose glucocorticoids (≤10 mg/day prednisone equivalent) immediately to control acute inflammation while adjusting the underlying DMARD strategy 1, 2
• Glucocorticoids should be tapered as rapidly as clinically feasible, ideally within 6 months, as they provide symptomatic relief but carry significant long-term toxicity 1, 2
• The EULAR guidelines emphasize that glucocorticoids combined with synthetic DMARDs show compelling evidence for superiority regardless of whether added to monotherapy or combination DMARD regimens 1

Step 2: Assess Disease Activity and Prognostic Factors

Evaluate the patient within 1-3 months to determine if DMARD escalation is needed 1, 2

Key prognostic factors to assess include:

• Presence of rheumatoid factor (RF) or anti-citrullinated peptide antibodies (ACPA), especially at high levels 1
• Very high disease activity state 1
• Early erosive disease or radiographic progression 1

DMARD Escalation Algorithm

If Patient is on Methotrexate Monotherapy:

For patients WITH poor prognostic factors:

• Add a biologic DMARD (bDMARD) to methotrexate immediately rather than switching to another conventional synthetic DMARD 1, 3
• First-line biologic options include TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, or tocilizumab, all combined with methotrexate 1, 4
• The combination of methotrexate with a bDMARD enhances efficacy and reduces development of neutralizing antibodies 2

For patients WITHOUT poor prognostic factors:

• Switch to leflunomide 20 mg daily or sulfasalazine as the next conventional synthetic DMARD before considering biologics 1, 4, 3
• Reassess disease activity at 3 months; if no improvement, escalate to biologic therapy 3
• If treatment target not reached by 6 months, change treatment strategy to include biologics 1, 3

If Patient is Already on Combination Therapy or Has Failed Multiple DMARDs:

For patients who have failed their first TNF inhibitor:

• Switch to either another TNF inhibitor OR a biologic with a different mechanism of action (abatacept, rituximab, or tocilizumab) 1
• Evidence suggests a tendency for non-TNFi biologics to be more effective than switching to another TNFi after first TNFi failure 5
• All currently used biologics and targeted synthetic DMARDs are more effective than placebo in patients who previously failed bDMARDs 5

For patients who have failed multiple biologics:

• Consider tofacitinib (JAK inhibitor) after biological treatment has failed 1
• Note that effectiveness generally decreases in patients who have failed a higher number of bDMARDs 5
• A subsequent bDMARD with a previously untargeted mechanism of action is somewhat more effective 5

Critical Monitoring Timeline

The treat-to-target approach requires strict adherence to monitoring intervals: 1, 2

• At 1-3 months: Assess disease activity; if no improvement, therapy MUST be adjusted immediately 1, 2
• At 3 months maximum: If no improvement is seen, this is the absolute deadline for treatment adjustment 1, 3
• At 6 months: If treatment target (remission or low disease activity) has not been reached, the treatment strategy must be changed 1, 3

Common Pitfalls to Avoid

• Do not continue ineffective therapy beyond 3 months without adjustment – this delays disease control and allows progressive joint damage 1, 2
• Do not use glucocorticoids as monotherapy – they must be combined with DMARDs and are only bridging therapy 2
• Do not neglect to optimize methotrexate dosing before declaring treatment failure – ensure the patient is on 20-25 mg weekly with folic acid supplementation 2, 6
• Do not delay biologic therapy in patients with poor prognostic factors – early aggressive treatment prevents disability 1

Special Considerations for Comorbidities

When escalating therapy, account for specific contraindications: 2

• Heart failure (NYHA class III or IV): Use non-TNF inhibitor biologics instead of TNF inhibitors 2
• Previous lymphoproliferative disorder: Rituximab is preferred over other DMARDs 2
• Hepatitis B infection: Provide prophylactic antiviral therapy when initiating rituximab or other biologics 2
• Nontuberculous mycobacterial lung disease: Add conventional synthetic DMARDs over biologics; if biologics needed, use abatacept 2
• Recent serious infection (within 12 months): Addition of/switching to DMARDs is preferred over glucocorticoid escalation 2

Non-Pharmacological Adjuncts

While adjusting pharmacological therapy, incorporate: 5

• Exercise interventions to improve functional disability, pain, and fatigue 5
• Psychological and educational interventions to improve self-management and goal setting 5
• These interventions specifically address non-inflammatory complaints that may persist despite optimal DMARD therapy 5