What is the treatment guideline for rheumatoid arthritis?

Treatment Guideline for Rheumatoid Arthritis

First-Line Treatment Strategy

Methotrexate should be initiated immediately upon diagnosis as the first-line DMARD for most patients with rheumatoid arthritis, rapidly escalated to 20-25 mg weekly (or maximum tolerated dose), and combined with short-term low-dose glucocorticoids as bridging therapy. 1, 2

Initial DMARD Selection and Dosing

• Start methotrexate at 7.5-10 mg weekly and rapidly escalate to 20-25 mg weekly within 4-6 weeks, as this represents the optimal therapeutic dose 2, 3
• Prescribe folic acid supplementation with all methotrexate therapy to reduce side effects 3, 4
• Consider subcutaneous administration if higher doses are needed or gastrointestinal side effects occur, as subcutaneous methotrexate shows superior bioavailability (85% ACR20 response) compared to oral administration (77%) 3, 5
• For patients with contraindications to methotrexate, use leflunomide, sulfasalazine, or hydroxychloroquine as alternative first-line conventional synthetic DMARDs 2, 6

Bridging Glucocorticoid Therapy

• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) when starting DMARDs in patients with moderate or high disease activity 1, 2
• Limit glucocorticoid duration to less than 3 months and taper as rapidly as clinically feasible to minimize long-term adverse effects including cataracts, osteoporosis, and cardiovascular disease 1, 2
• Use glucocorticoids at the lowest possible dose and shortest duration to optimize the benefit-risk ratio 1

Treat-to-Target Approach

Monitor disease activity every 1-3 months using validated measures (SDAI, CDAI, or DAS28) and escalate therapy if the treatment target is not achieved within 3-6 months. 1, 2

• The treatment target should be remission or low disease activity 1, 2
• If no improvement occurs by 3 months, adjust therapy immediately 3
• If the target is not reached by 6 months, escalate treatment 3

Treatment Escalation Algorithm

For Inadequate Response to Methotrexate Monotherapy

If methotrexate monotherapy fails after 3 months in patients with moderate-to-high disease activity, add a biologic DMARD (preferably a TNF inhibitor) or targeted synthetic DMARD in combination with methotrexate. 1, 2

• TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol) are the preferred first biologic agents 2, 3
• Biologic therapy should be used in combination with methotrexate when possible, as this combination demonstrates superior efficacy over biologic monotherapy 1
• Alternative first-line biologics include IL-6 inhibitors (tocilizumab, sarilumab), which are effective as monotherapy or in combination with methotrexate 2
• JAK inhibitors (tofacitinib, baricitinib) represent another option for patients with inadequate response to conventional synthetic DMARDs 2, 7

For Inadequate Response to First Biologic

If a TNF inhibitor fails, switch to either a different TNF inhibitor (effective in 50-70% of cases) or to a non-TNF biologic with a different mechanism of action. 2

• Non-TNF biologic options include:
  • Abatacept (T-cell costimulation modulator) 2
  • Tocilizumab or sarilumab (IL-6 receptor antagonists) 2
  • Rituximab (anti-CD20 antibody) 2
• After sequential failure of both a TNF inhibitor and abatacept, rituximab is recommended for patients with high disease activity 2

Biomarker-Guided Selection

• Patients who are rheumatoid factor positive, anti-CCP antibody positive, or have elevated serum IgG may respond better to rituximab 2
• Seronegative patients may respond better to abatacept or tocilizumab 2

Treatment in Special Populations

Heart Failure (NYHA Class III or IV)

• Use non-TNF inhibitor biologics or targeted synthetic DMARDs instead of TNF inhibitors, as TNF inhibitors can worsen heart failure 1, 3
• If a patient develops heart failure while taking a TNF inhibitor, switch to a non-TNF biologic or targeted synthetic DMARD 1

Hepatitis B Infection

• Strongly recommend prophylactic antiviral therapy (not just monitoring) for patients initiating rituximab who are hepatitis B core antibody positive, regardless of surface antigen status 1
• Strongly recommend prophylactic antiviral therapy for patients initiating any biologic or targeted synthetic DMARD who are both hepatitis B core antibody positive and surface antigen positive 1
• For patients initiating biologics other than rituximab who are hepatitis B core antibody positive but surface antigen negative, frequent monitoring of viral load and liver enzymes is conditionally recommended over prophylactic therapy 1

Previous Lymphoproliferative Disorder

• Rituximab is conditionally recommended over other DMARDs for patients with a previous lymphoproliferative disorder for which rituximab is an approved treatment 1, 2

Serious Infection History

• For patients with serious infection within the previous 12 months, addition of or switching to DMARDs is conditionally recommended over initiation or dose escalation of glucocorticoids 3

Nontuberculous Mycobacterial Lung Disease

• Add conventional synthetic DMARDs over biologics or targeted synthetic DMARDs 3
• If biologics are needed, abatacept is conditionally recommended over other options 3

Monitoring Requirements

Baseline Assessment

• Complete blood count with differential and platelet counts 4
• Hepatic enzymes and renal function tests 4
• Chest X-ray 4
• Tuberculosis screening (TST or IGRA) before initiating biologics or JAK inhibitors 1, 2
• Hepatitis B and C screening before initiating biologics 1, 2

Ongoing Monitoring

• Hematology at least monthly 4
• Renal function and liver function every 1-2 months 4
• Disease activity assessment every 1-3 months using validated measures 2, 3
• More frequent monitoring during dose changes or periods of increased risk 4

Treatment Tapering

For patients in sustained remission (at least 6 months of low disease activity or remission), consider cautious de-escalation of therapy through shared decision-making. 8, 2

• Taper glucocorticoids first before considering DMARD tapering 8
• Taper biologics before tapering conventional synthetic DMARDs 8
• Monitor disease activity frequently (every 1-3 months) during tapering 8
• Approximately 15-25% of patients may achieve sustained drug-free remission, particularly those with shorter symptom duration, absence of rheumatoid factor or anti-CCP antibodies, lower disease activity before remission, and less baseline disability 2

Common Pitfalls to Avoid

• Delaying DMARD initiation leads to irreversible joint damage and worse long-term outcomes 2, 7
• Using inadequate methotrexate dosing (less than 20-25 mg weekly) or insufficient duration of treatment trial (less than 3 months at optimal dose) before concluding treatment failure 2, 9
• Prescribing methotrexate without folic acid supplementation, leading to unnecessary side effects 3, 4
• Continuing long-term glucocorticoid use beyond 1-2 years without appropriate monitoring for adverse effects including cataracts, osteoporosis, and cardiovascular disease 2
• Failing to adjust therapy when treatment targets are not met within 3-6 months 2, 3
• Overlooking comorbidities that influence treatment selection, such as hepatitis B (requiring prophylactic antivirals with rituximab), tuberculosis (requiring screening before biologics), or heart failure (avoiding TNF inhibitors) 1, 2
• Mistaken daily use of methotrexate instead of weekly dosing, which has led to fatal toxicity—prescriptions should not be written on a PRN basis 4
• Using TNF inhibitors in patients with NYHA class III or IV heart failure, as this can worsen heart failure 1
• Failing to monitor disease activity regularly and adjust therapy accordingly 2, 3