Treatment of Enthesopathy
NSAIDs are the first-line pharmacological treatment for enthesopathy, followed by local glucocorticoid injections when NSAIDs are insufficient, and biological DMARDs (particularly TNF inhibitors) should be initiated when both NSAIDs and local injections fail to control symptoms. 1
Initial Management Strategy
First-Line Therapy
NSAIDs should be initiated as the primary pharmacological treatment for all patients with enthesopathy, regardless of whether the condition is inflammatory or mechanical in nature 2, 1
Local glucocorticoid injections directed to the specific site of inflammation are recommended as adjunctive therapy or when NSAIDs provide inadequate relief 2, 1
- Important caveat: Avoid peri-tendon injections of the Achilles, patellar, and quadriceps tendons due to risk of tendon rupture 2
Physical therapy with supervised exercise programs should be incorporated early, as active interventions are superior to passive modalities like massage or ultrasound 2, 1
Second-Line Therapy
Conventional Synthetic DMARDs
Conventional synthetic DMARDs (csDMARDs) have limited efficacy specifically for enthesitis and should not be relied upon as primary treatment 1
Sulfasalazine may be considered for peripheral enthesitis in the context of psoriatic arthritis, but evidence shows inconsistent results and it is not a preferred option 2, 1
Methotrexate is preferred only when there is concomitant significant skin involvement (psoriasis) or peripheral arthritis, not for isolated enthesopathy 2, 1
Third-Line Therapy
Biological DMARDs
When NSAIDs and local glucocorticoid injections are insufficient, biological DMARDs should be initiated 2, 1
TNF inhibitors (infliximab, etanercept, adalimumab) are the preferred first biological agents according to current practice patterns 2, 1
IL-17 inhibitors (secukinumab, ixekizumab) are appropriate alternatives, particularly in patients with contraindications to TNF inhibitors (recurrent infections, congestive heart failure, demyelinating disease) or those with severe concomitant psoriasis 2, 1
IL-12/23 inhibitors (ustekinumab) may be considered but are generally less preferred than TNF or IL-17 inhibitors for enthesopathy 2, 1
All biological DMARDs demonstrate similar efficacy for enthesitis when compared head-to-head 1
Clinical Context Considerations
Inflammatory vs. Mechanical Enthesopathy
Distinguish inflammatory enthesitis from mechanical enthesopathy by evaluating for asymmetrical distribution of painful entheses and presence of clinical swelling, which suggest inflammatory disease 1
Mechanical enthesopathy typically responds adequately to NSAIDs, local injections, and physical therapy without requiring escalation to biologics 3, 4
Enthesopathy in Spondyloarthropathies
For enthesopathy associated with ankylosing spondylitis or psoriatic arthritis, the treatment ladder should progress from NSAIDs → local injections → TNF inhibitors 2, 1
In patients with predominant axial disease and enthesitis who fail NSAIDs, TNF inhibitors are the established standard of care 2
Special Populations
Concomitant fibromyalgia can complicate assessment and may cause overestimation of disease severity; this should be recognized to avoid unnecessary escalation of immunosuppressive therapy 1
In patients with inflammatory bowel disease, avoid IL-17 inhibitors and preferentially use TNF inhibitors or IL-12/23 inhibitors 2
Common Pitfalls
Avoid systemic glucocorticoids for routine management of enthesopathy, as they are strongly recommended against in the context of spondyloarthropathies 2
Do not rely on conventional DMARDs as monotherapy for enthesitis, as they have minimal direct effect on entheseal inflammation 1
Recognize that the natural history of many enthesopathies (particularly mechanical ones like lateral epicondylitis) is spontaneous resolution, and invasive treatments have not been proven to alter this natural course 5