What is the recommended treatment for enthesitis?

Treatment of Enthesitis

For enthesitis treatment, locally administered parenteral glucocorticoid injections are conditionally recommended as first-line therapy for patients with stable axial disease and active enthesitis that persists despite NSAID treatment, though injections around Achilles, patellar, and quadriceps tendons should be avoided due to risk of tendon rupture. 1

First-Line Treatment Options

NSAIDs

• NSAIDs are the initial treatment of choice for mild to moderate enthesitis 1
• Should be tried for at least 4 weeks to properly assess response
• Can be combined with physical therapy and education 1

Local Measures

• Physical therapy is recommended to improve function and reduce mechanical factors contributing to entheseal inflammation 2
• Local cryotherapy may provide symptomatic relief and has shown benefits in case reports 3
• For persistent symptoms, locally administered parenteral glucocorticoid injections can be considered, with important caveats:
  • Avoid injections around Achilles, patellar, and quadriceps tendons due to risk of rupture 1
  • Consider injections at safer sites such as greater trochanter, pelvic rim, and plantar fascia attachment 1
  • Ultrasound guidance is strongly recommended for accurate placement and to confirm inflammation 4
  • Perientheseal injections are preferable to intraentheseal injections 4

Second-Line Treatment Options

DMARDs

• For moderate enthesitis with inadequate response to NSAIDs and local measures, conventional DMARDs may be considered 1
• However, evidence for conventional DMARDs in isolated enthesitis is limited

PDE4 Inhibitors

• In patients with mild disease and inadequate response to at least one csDMARD, PDE4 inhibitors (apremilast) may be considered, particularly for oligoarticular or entheseal disease without poor prognostic factors 1

Third-Line Treatment Options

Biologic DMARDs

• For severe or refractory enthesitis with insufficient response to NSAIDs or local glucocorticoid injections, biologic DMARDs should be considered 1
• TNF inhibitors (etanercept, adalimumab, infliximab, golimumab) have demonstrated efficacy in enthesitis 1, 5
• IL-17 inhibitors are also effective options, particularly when there is concomitant axial disease 1
• All currently approved bDMARDs have demonstrated similar efficacy for enthesitis, though head-to-head trials are lacking 1

JAK Inhibitors

• JAK inhibitors may be considered for enthesitis, though safety issues should be evaluated 1
• These are typically considered after failure of other therapies

Treatment Algorithm

1. Initial approach: NSAIDs + physical therapy/cryotherapy for 4 weeks
2. If inadequate response: Consider local glucocorticoid injections (avoiding high-risk sites)
3. If still inadequate:
   • For mild disease: Consider PDE4 inhibitors
   • For moderate-severe disease: Progress to biologic therapy (TNF inhibitors or IL-17 inhibitors)
4. For enthesitis with axial involvement: Consider IL-17 inhibitors, TNF inhibitors, or JAK inhibitors

Important Considerations

• Ultrasound or MRI assessment is valuable to confirm enthesitis diagnosis and rule out other causes of entheseal pain 4, 6
• The decision for entheseal injection should be made on an individual basis, after more conservative measures have failed 4
• High-risk patients (those with existing tendon damage) should avoid entheseal injections 4
• Treatment approach may differ based on associated conditions (psoriatic arthritis, ankylosing spondylitis, etc.) 1

The evidence supporting these recommendations is generally of low to very low quality, with most recommendations being conditional rather than strong 1. Treatment decisions should consider the specific enthesitis location, severity, and associated conditions.