What is rheumatoid arthritis and its latest management regimen?

Rheumatoid Arthritis: Definition and Latest Management

Definition

Rheumatoid arthritis is a chronic, progressive autoimmune disease characterized by inflammation principally in synovial joints, resulting from an incompletely understood pathophysiological mechanism that leads to pain, disability, and potential systemic complications if left untreated. 1, 2

• The disease affects over 400,000 people in the United Kingdom alone and represents the most common autoimmune, destructive, inflammatory arthritis in adults 1, 3
• RA manifests with symmetric polyarthritis, joint swelling, and morning stiffness lasting 1 hour or longer 2
• Systemic manifestations include fatigue and low-grade fever 2
• Without prompt treatment, permanent joint damage, rheumatoid vasculitis, and other severe complications can develop 4

Latest Management Regimen

Early Recognition and Urgent Referral

Refer urgently to a rheumatologist anyone with suspected persistent synovitis, even with normal acute-phase response or negative rheumatoid factor, particularly when small joints of hands/feet are affected, more than one joint is involved, or there has been a delay of three months or longer between symptom onset and seeking medical advice. 1

• Test for rheumatoid factor in all patients with suspected RA who have synovitis 1
• Measure anti-cyclic citrullinated peptide (anti-CCP) antibodies if rheumatoid factor is negative and combination therapy is being considered 1

First-Line Treatment Strategy

Start methotrexate 15 mg weekly with folic acid 1 mg daily immediately upon diagnosis as the cornerstone of initial therapy. 5, 6, 3

• Methotrexate should be part of the first treatment strategy in all newly diagnosed RA cases 5, 6, 7
• Increase methotrexate dose to 20-25 mg weekly or maximal tolerated dose if inadequate response, then switch to subcutaneous administration if needed 1
• Baseline laboratory monitoring must include CBC, liver enzymes, creatinine, and hepatitis B/C screening 5
• NSAIDs, low-dose glucocorticoids, and aspirin may be continued concomitantly, though increased toxicity risk exists 6

Treatment Goals and Monitoring

The primary goal is achieving clinical remission (SDAI ≤3.3 or CDAI ≤2.8) or low disease activity (SDAI ≤11 or CDAI ≤10), with disease activity assessed monthly for high/moderate activity and every 3-6 months for low activity/remission. 1, 2, 5

• Treatment must be adjusted at least every 3 months until target is reached 2
• Any new treatment should be tried for at least 3-6 months to fully assess efficacy 1
• Regular assessment includes tender/swollen joint counts, pain scales, and functional status 5

Treatment Escalation Algorithm

For patients with inadequate response to methotrexate monotherapy after 3-6 months, initiate triple-DMARD therapy by adding sulfasalazine and hydroxychloroquine to optimize methotrexate. 1

• Triple-DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) is the next step before biologics 1
• Hydroxychloroquine dosage: 200-400 mg daily (not exceeding 5 mg/kg actual weight to reduce retinopathy risk) 8
• Sulfasalazine is added as part of the triple-DMARD regimen 1

Biologic and Targeted Synthetic DMARDs

If triple-DMARD therapy fails, switch to biologic agents, starting with anti-TNF inhibitors (up to 2 trials), then alternative mechanisms including abatacept (CTLA4:Ig), tocilizumab (anti-IL-6R), rituximab (anti-CD20), or anakinra (IL-1ra). 1, 7

• Rheumatoid factor positive patients, those with anti-citrullinated protein antibodies, or elevated serum IgG respond favorably to rituximab 1
• Seronegative patients with inadequate anti-TNF response should receive abatacept or tocilizumab rather than rituximab 1
• When switching biologics, preferably choose one with an alternative mechanism of action 1

Glucocorticoid Management

Use short-term glucocorticoids as bridging therapy during DMARD initiation, then taper and discontinue once remission is achieved, as long-term use (beyond 1-2 years) increases risks of cataracts, osteoporosis, fractures, and cardiovascular disease. 1, 9

• Intra-articular glucocorticoid injections for isolated joint inflammation 1
• Taper/discontinue prednisone once remission is achieved 1

Remission and De-escalation

For patients achieving sustained remission ≥1 year, consider careful de-escalation of therapy, as 15-25% may achieve sustained drug-free remission, though most will require resumption of treatment without radiologic progression. 1

• Continue current DMARD regimen if in remission 1
• Shorter symptom duration, absence of rheumatoid factor/ACPA, lower baseline disease activity, and less baseline disability predict successful drug-free remission 1
• Most patients experiencing flare-up after 3-6 months achieve remission again with treatment resumption without radiologic progression 1

Non-Pharmacological Management

Implement thermal modalities, joint protection techniques, activity pacing, regular aerobic and resistance exercise programs, appropriate splinting/orthoses, and assistive devices to address mechanical symptoms from structural joint damage. 2

• Mechanical symptoms (joint instability, deformity, limited range of motion, weight-bearing pain) require physical interventions beyond anti-inflammatory therapy 2
• Rest and physiotherapy should be continued throughout treatment 6

Critical Pitfalls to Avoid

• Do not delay referral based on normal inflammatory markers or negative rheumatoid factor, as early aggressive treatment prevents irreversible joint damage 1
• Do not use inadequate methotrexate doses; escalate to 20-25 mg weekly before declaring treatment failure 1, 3
• Do not continue ineffective therapy beyond 3 months without escalation 2, 3
• Do not fail to distinguish inflammatory from mechanical symptoms, as mechanical symptoms require different management approaches and won't respond to anti-inflammatory therapy alone 2
• Do not use long-term glucocorticoids beyond 1-2 years due to significant adverse effects 1
• Do not overlook the importance of treat-to-target strategy with frequent monitoring and rapid treatment adjustments 2, 3