What is the recommended treatment for Enthesitis-related arthritis (ERA)?

Treatment Recommendations for Enthesitis-Related Arthritis (ERA)

For patients with enthesitis-related arthritis (ERA), TNF inhibitors are strongly recommended as the treatment of choice when NSAIDs are insufficient, as they are more effective than conventional DMARDs for controlling enthesitis and preventing disease progression. 1

Initial Assessment and Classification

• ERA is a specific subtype of juvenile idiopathic arthritis (JIA) characterized by:

  • Arthritis and enthesitis (inflammation at tendon-to-bone insertion sites)
  • Often HLA-B27 positive (in approximately 60% of cases) 2
  • Predominantly affects males
  • May involve sacroiliitis and axial disease
  • Asymmetric oligoarthritis or polyarthritis, predominantly of lower limbs 3

• Key clinical features to evaluate:

  • Number and pattern of affected joints (particularly lower limb involvement)
  • Presence of enthesitis (tenderness/swelling at entheseal sites)
  • Inflammatory back pain or sacroiliitis
  • Extra-articular manifestations (uveitis, inflammatory bowel disease) 4

Treatment Algorithm

First-Line Therapy

1. NSAIDs
   • Strongly recommended as initial therapy for active enthesitis 1
   • Continue for up to 2 months if effective 1
   • If inadequate response after 2 months, escalate therapy

Second-Line Therapy (for inadequate response to NSAIDs)

1. TNF inhibitors

   • Conditionally recommended over methotrexate or sulfasalazine for patients with active enthesitis despite NSAID treatment 1
   • More effective for enthesitis than conventional DMARDs
   • Consider earlier for patients with:
     • High disease activity
     • Axial involvement/sacroiliitis
     • Multiple sites of enthesitis

2. Sulfasalazine

   • Alternative option for patients with contraindications to TNF inhibitors
   • Particularly for peripheral arthritis component of ERA 1
   • Less effective for enthesitis and axial disease

3. Methotrexate

   • May be considered for patients with predominant peripheral arthritis
   • Limited efficacy for enthesitis and axial disease

Adjunctive Therapies

• Corticosteroid injections

  • Conditionally recommended for sacroiliac joints in active sacroiliitis 1
  • Consider for persistent, localized enthesitis

• Physical therapy

  • Conditionally recommended for all ERA patients 1
  • Particularly important for those with axial involvement or functional limitations

• Bridging oral glucocorticoids

  • Short course (<3 months) conditionally recommended during initiation or escalation of therapy 1
  • Most useful for high disease activity, limited mobility, or significant symptoms

TNF Inhibitor Selection and Combination Therapy

• Adalimumab + methotrexate combination shows superior drug survival compared to adalimumab monotherapy or etanercept-based regimens 5
• Adalimumab has longer median time to treatment discontinuation (4.9 years) compared to etanercept (2 years) 5
• HLA-B27 positivity is associated with better response to TNF inhibitors 5

Monitoring and Prognostic Factors

• Disease activity monitoring:

  • Clinical Juvenile Arthritis Disease Activity Score (cJADAS-10)
  • Regular assessment of enthesitis sites
  • Inflammatory markers (ESR, CRP)

• Poor prognostic factors:

  • Hip or ankle involvement
  • Restricted spinal mobility
  • Axial involvement (sacroiliitis/spinal disease)
  • Extra-articular manifestations 4
  • Elevated CRP (≥12.15 mg/L) in axial ERA 5

Important Clinical Considerations

• ERA patients with extra-articular manifestations (IBD, uveitis, SAPHO syndrome) have worse prognosis and require earlier biologic therapy 4
• Patients with axial involvement have poorer response to conventional DMARDs and should be considered for earlier TNF inhibitor therapy 5
• Ultrasound can detect subclinical enthesitis and guide treatment decisions 3
• MRI is essential for evaluating sacroiliitis and axial involvement 3

Emerging Therapies

• IL-17/IL-23 inhibitors and JAK inhibitors show promise for ERA treatment, particularly for patients with inadequate response to TNF inhibitors 6
• These newer agents may be particularly beneficial for patients with axial disease or enthesitis 1

ERA patients generally have poorer long-term outcomes compared to other JIA subtypes, highlighting the importance of early, aggressive therapy to prevent disease progression and disability 3.