What is the stepwise treatment protocol for Rheumatoid Arthritis (RA)?

Stepwise Treatment Protocol for Rheumatoid Arthritis

The stepwise treatment protocol for rheumatoid arthritis begins with methotrexate as first-line therapy, followed by combination conventional DMARDs if inadequate response occurs, and then progresses to biologic or targeted synthetic DMARDs for persistent moderate to high disease activity. 1

Initial Treatment Approach

• Treatment with disease-modifying antirheumatic drugs (DMARDs) should be started as soon as the diagnosis of RA is made to prevent joint damage and disability 2
• Methotrexate (MTX) should be part of the first treatment strategy in patients with active RA, optimized to 15-25 mg weekly as tolerated 2, 1
• For patients with contraindications or intolerance to MTX, alternative first-line DMARDs include leflunomide, sulfasalazine, or hydroxychloroquine 2
• Low-dose glucocorticoids should be considered as part of the initial treatment strategy for up to 6 months in combination with DMARDs, but should be tapered as rapidly as clinically feasible 2, 1
• Treatment should aim at reaching a target of remission or low disease activity as soon as possible in every patient 2

Monitoring and Treatment Adjustment

• Monitoring should be frequent in active disease (every 1-3 months); if there is no improvement by at most 3 months after treatment initiation or the target has not been reached by 6 months, therapy should be adjusted 2
• Disease activity should be measured using validated instruments such as the Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI) 2, 1
• For patients with persistent low disease activity (SDAI ≤11 or CDAI ≤10) despite MTX monotherapy, consider optimization of DMARD therapy 2

Treatment Escalation for Inadequate Response to Initial Therapy

• If the treatment target is not achieved with the first DMARD strategy and poor prognostic factors are absent, consider switching to another conventional synthetic DMARD strategy 2
• For patients with moderate disease activity (SDAI >11 to ≤26 or CDAI >10 to ≤22) despite optimized MTX, consider:
  • Adding sulfasalazine and hydroxychloroquine (triple therapy) 2
  • Switching to subcutaneous MTX if oral MTX was used initially 2
• When poor prognostic factors are present or there is persistent moderate to high disease activity despite conventional DMARDs, consider adding a biologic DMARD 2
• First-line biologic options include:
  • TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) 2, 3
  • T-cell costimulation modulator (abatacept) 2, 4
  • Biologic DMARDs should typically be combined with MTX for optimal efficacy 2

Treatment for Inadequate Response to First Biologic

• If a first biologic DMARD has failed, patients should receive another biologic DMARD 2
• If a first TNF inhibitor therapy has failed, patients may receive:
  • Another TNF inhibitor (up to 2 trials) 2
  • A biologic with another mechanism of action: abatacept, tocilizumab (IL-6 receptor antagonist), or rituximab (anti-CD20) 2
• Rituximab may be particularly effective in seropositive patients (positive rheumatoid factor or anti-citrullinated protein antibodies) 2, 1
• For seronegative patients with inadequate response to TNF inhibitors, abatacept or tocilizumab may be preferred 2
• Tofacitinib (JAK inhibitor) may be considered after biological treatment has failed 2

Treatment in Remission or Low Disease Activity

• If a patient is in persistent remission after having tapered glucocorticoids, consider tapering biologic DMARDs, especially if combined with a conventional synthetic DMARD 2
• In cases of sustained long-term remission (≥1 year), cautious reduction of conventional synthetic DMARD dose could be considered 2, 1
• For patients in remission, continue current DMARD regimen, taper/discontinue prednisone, and if sustained remission ≥1 year, consider de-escalation of therapy (≤1 trial) 2

Common Pitfalls and Considerations

• Delaying DMARD initiation can lead to irreversible joint damage and worse long-term outcomes 1
• Inadequate methotrexate dosing (less than 15-25 mg weekly) or insufficient duration of treatment trial (less than 3-6 months) before concluding treatment failure 2, 1
• Long-term glucocorticoid use without appropriate monitoring for adverse effects 1
• Failure to adjust therapy when treatment targets are not met 2, 1
• Overlooking comorbidities that may influence treatment selection, such as hepatitis, tuberculosis, or heart failure 1
• Patients starting biologic therapy should be screened for tuberculosis and hepatitis B/C 1

This stepwise approach to RA treatment emphasizes early intervention, treat-to-target strategy, and appropriate escalation of therapy to achieve remission or low disease activity, which has been demonstrated to improve long-term outcomes and quality of life for patients with RA 1, 5.