How should rheumatoid arthritis be treated and managed, including lifestyle measures, NSAIDs, glucocorticoids, conventional synthetic disease‑modifying antirheumatic drugs (e.g., methotrexate), and biologic or targeted synthetic disease‑modifying antirheumatic drugs?

Rheumatoid Arthritis Treatment and Management

Immediate Treatment Initiation

Start methotrexate immediately upon diagnosis of rheumatoid arthritis at 7.5-10 mg weekly, rapidly escalate to 20-25 mg weekly within 4-6 weeks, and add short-term low-dose glucocorticoids as bridging therapy for up to 6 months. 1, 2

• Therapy with DMARDs must begin as soon as the diagnosis is made—do not delay treatment 1
• The optimal methotrexate dose is 25-30 mg weekly with folate supplementation, recognizing that maximum effect requires 4-6 months 1
• Subcutaneous methotrexate may be used if oral dosing causes intolerable side effects 3

Treatment Target and Monitoring Strategy

Aim for sustained remission or low disease activity as the treatment target in every patient, with mandatory reassessment every 1-3 months during active disease. 1

• If no improvement occurs by 3 months after treatment initiation, therapy must be adjusted immediately 1, 2
• If the treatment target is not reached by 6 months, escalate therapy 1
• Use validated composite measures (DAS28, SDAI, or CDAI) to assess disease activity 4, 2

First-Line Treatment Alternatives

If methotrexate is contraindicated or not tolerated early, use leflunomide or sulfasalazine as the first-line conventional synthetic DMARD. 1, 2

• Leflunomide 20 mg daily is the preferred alternative after methotrexate failure in patients without poor prognostic factors 5
• Sulfasalazine is another acceptable alternative, though combinations of sulfasalazine with leflunomide (except with methotrexate) have not been well studied 1

Glucocorticoid Use

Add low-dose glucocorticoids at treatment initiation in combination with conventional synthetic DMARDs, but taper as rapidly as clinically feasible within 6 months. 1

• Glucocorticoids can be administered in different dose regimens and routes (oral, intramuscular, intra-articular) 1
• Short-term glucocorticoids should be considered when initiating or changing conventional synthetic DMARDs 1
• All glucocorticoids must be tapered and discontinued before considering tapering of other DMARDs 4, 2

Escalation to Biologic or Targeted Synthetic DMARDs

Add a biologic DMARD (TNF inhibitor, abatacept, tocilizumab, or rituximab) or JAK inhibitor combined with methotrexate if the treatment target is not achieved with first-line conventional synthetic DMARDs and poor prognostic factors are present. 1, 2

Poor Prognostic Factors Include:

• High levels of rheumatoid factor or anti-citrullinated protein antibodies 1
• Very high disease activity 1
• Early joint damage on imaging 1

Biologic DMARD Options:

• TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or approved biosimilars) are preferred first-line biologics 1, 2
• Non-TNF biologics include abatacept, tocilizumab, sarilumab, and rituximab (under certain circumstances such as history of lymphoma or demyelinating disease) 1
• JAK inhibitors (targeted synthetic DMARDs) may be considered, particularly after biologic failure 1, 2

Combination Therapy Requirements:

• Biologics and JAK inhibitors should be combined with a conventional synthetic DMARD (preferably methotrexate) 1, 3
• In patients who cannot use conventional synthetic DMARDs as comedication, IL-6 pathway inhibitors and JAK inhibitors may have advantages over other biologics 1

Management After Biologic Failure

If a first biologic DMARD or JAK inhibitor fails, switch to another biologic DMARD or JAK inhibitor; after TNF inhibitor failure, either use another TNF inhibitor or switch to a biologic with a different mechanism of action. 1, 2

• Multiple successive drug options are often needed to reach the therapeutic goal—this is expected and does not represent treatment failure 1
• Cycling between drugs is sometimes necessary as early as every 3 months if improvement is insufficient 1
• A different drug from the same class can still be efficacious after failure of the first agent 1

Treatment Tapering in Remission

In patients achieving persistent remission for at least 6 months, taper in the following sequence: first glucocorticoids, then biologics/JAK inhibitors, and finally conventional synthetic DMARDs. 4, 2

Glucocorticoid Tapering:

• Taper glucocorticoids first and discontinue completely before considering other medication reductions 4

Biologic/JAK Inhibitor Tapering:

• Consider tapering biologics or JAK inhibitors after achieving persistent remission and after glucocorticoids are discontinued, especially if combined with a conventional synthetic DMARD 1
• Tapering can involve dose reduction or prolongation of intervals between applications 1

Conventional Synthetic DMARD Tapering:

• Methotrexate tapering should only occur after persistent remission for at least 6 months and after glucocorticoids and biologics are tapered 4
• Reduce methotrexate dose by 50% initially rather than stopping completely 4
• Monitor disease activity every 1-3 months during tapering; if disease activity increases, immediately return to the previous effective dose 4

Absence of Poor Prognostic Factors

If the treatment target is not achieved with first-line conventional synthetic DMARD therapy and poor prognostic factors are absent, switch to another conventional synthetic DMARD strategy before adding biologics. 1, 5

• This may include switching to leflunomide or sulfasalazine monotherapy 5
• Combination therapy with multiple conventional synthetic DMARDs can be considered 1

Special Considerations

Treatment decisions must be made through shared decision-making between patient and rheumatologist, considering disease activity, structural damage progression, comorbidities, and safety issues. 1

• Rheumatologists are the specialists who should primarily care for rheumatoid arthritis patients 1
• Economic costs (individual, societal, and medical) should be considered in management decisions 1
• Continuing a partially failing DMARD can be as costly as switching to another DMARD 1

Common Pitfalls to Avoid

• Do not delay DMARD initiation while waiting for definitive diagnosis—early treatment within months of presentation prevents irreversible joint damage 3, 6
• Do not use NSAIDs or glucocorticoids as monotherapy—these control symptoms but do not prevent disease progression 7, 8
• Do not continue ineffective therapy beyond 3-6 months—this leads to preventable disability 1, 2
• Do not taper medications in the wrong sequence—always taper glucocorticoids first, then biologics, then conventional synthetic DMARDs 4, 2
• Do not attempt tapering with remission duration less than 6 months or in patients still requiring glucocorticoids 4