What is the recommended treatment for inflammatory arthritis?

Treatment for Inflammatory Arthritis

Methotrexate 15-25 mg weekly is the first-line treatment for inflammatory arthritis, with rapid escalation to the maximum tolerated dose within 4-8 weeks, targeting remission or low disease activity assessed every 3 months. 1, 2

Initial Treatment Strategy

• Start methotrexate immediately at 15 mg/week orally and rapidly escalate to 20-25 mg/week (or maximum tolerated dose) within 4-8 weeks 1, 2
• Continue NSAIDs, analgesics, and/or glucocorticoids for symptomatic relief during DMARD initiation 1, 3
• For patients with high disease activity and poor prognostic features, initiate methotrexate without prior NSAID trial 3
• Methotrexate has the best efficacy/toxicity ratio among conventional DMARDs and serves as the anchor treatment 1, 4, 5

Disease Activity Monitoring and Treatment Targets

• Measure disease activity every 3 months using SDAI (Simplified Disease Activity Index) or CDAI (Clinical Disease Activity Index) 1, 2
• Target remission (SDAI ≤3.3 or CDAI ≤2.8) or low disease activity (SDAI ≤11 or CDAI ≤10) 1, 2
• Continue current regimen if target is achieved; taper and discontinue prednisone if in sustained remission 1

Treatment Escalation at 6-12 Months

If Target NOT Attained (SDAI >11 or CDAI >10):

For moderate disease activity (SDAI 11-26):

• Add sulfasalazine + hydroxychloroquine (triple therapy) OR switch to subcutaneous methotrexate 1

For persistent moderate-to-high disease activity:

• Add TNF inhibitor (adalimumab, etanercept) as first biologic option 1, 6
• Alternative: Add abatacept (CTLA4:Ig) 1
• After inadequate response to ≥1 TNF inhibitor: Add tocilizumab (anti-IL-6R) or rituximab (anti-CD20) 1, 2

The 2021 American College of Rheumatology guideline strongly supports this stepwise approach, with TNF inhibitors and abatacept as approved first-line biologics 1. Methotrexate should be continued with biologics to reduce immunogenicity and improve efficacy 2.

Beyond 12 Months: Refractory Disease

• Optimize methotrexate to 20-25 mg/week subcutaneously before declaring treatment failure 1, 2
• Consider intra-articular glucocorticoid injections for isolated joint inflammation 1
• Switch to alternative biologic with different mechanism of action if current biologic fails 1, 2
• For seronegative patients (RF-negative) with inadequate anti-TNF response: prefer abatacept or tocilizumab over rituximab 1
• For seropositive patients (RF-positive, anti-CCP positive): rituximab is highly effective 1

Special Populations

Pulmonary disease:

• Methotrexate is conditionally recommended even with mild, stable lung disease, but inform patients of increased pneumonitis risk 1

Heart failure (NYHA Class III-IV):

• Use non-TNF biologics (abatacept, tocilizumab, rituximab) instead of TNF inhibitors 1

Progressive subcutaneous nodules on methotrexate:

• Switch to non-methotrexate DMARD 1

Critical Timing Considerations

• Allow 3-6 months to fully assess efficacy of any new DMARD or biologic before switching 1, 2
• Continuing NSAID monotherapy beyond 2 months in active arthritis is inappropriate 3
• Patients with persistent moderate-to-high disease activity beyond 1 year are at substantial risk of progression and require aggressive treatment escalation 1

Common Pitfalls to Avoid

• Do not use inadequate methotrexate doses (<20 mg/week) before declaring failure 1, 2
• Do not switch to oral methotrexate to subcutaneous route without first optimizing oral dosing 1
• Do not use anakinra (IL-1 inhibitor) as it is less effective than other biologics 1
• Do not abruptly discontinue DMARDs in patients at target; gradual discontinuation is preferred over abrupt cessation 1
• Do not fail to assess cardiovascular, renal, and gastrointestinal risks before prescribing NSAIDs 3