NSAIDs work by downregulating PGE2 production, an early mediator of entheseal inflammation. Ultrasonography studies have shown NSAIDs decrease vasodilation and inflammation at entheses.17 Note: Once enthesitis becomes chronic, it is anecdotally harder to treat and less responsive to NSAIDs.
You Might Also Like
Explore This IssueSeptember 2018
Conventional synthetic DMARDs are generally not efficacious for enthesitis, and switching to a biologic therapy as a next step is reasonable. TNF inhibitors have shown benefit for both axial and peripheral enthesitis in a variety of studies (though they were not designed to look at this as a primary outcome). Infliximab, adalimumab, etanercept, golimumab and certolizumab are all viable options, though head-to-head comparisons have not been made between these drugs for clinical dactylitis and enthesitis.18-22
MRI studies of patients with spondyloarthritis (predominantly of the ankylosing spondylitis subset) have shown improvement of peripheral joint, sacroiliac joint and vertebral body peri-entheseal osteitis with TNF inhibitors.23 Secukinumab, ixekizumab (which are anti-IL-17A inhibitors) and ustekinumab (an anti-IL12/23 inhibitor) have also shown efficacy in both clinical dactylitis and enthesitis.24-26
GRAPPA recommends switching to alternate mechanisms of action if TNF inhibitors fail to provide adequate relief. Apremilast, an oral phosphodiesterase 4 inhibitor, has been shown to have some efficacy in axial enthesitis (MASES). Apremilast decreases the production of several cytokines involved in entheseal inflammation (IL-17A, IL-23 and TNF-α), and also decreases neutrophil migration to the entheseal complex. A study of 504 patients showed improvement in axial enthesitis in about half of study participants by 12 months of therapy.27 More studies are needed to determine how effective apremilast is for peripheral enthesitis and for dactylitis.
Tofacitinib, a JAK inhibitor approved for treating PsA, showed numerical benefits in enthesitis and dactylitis, which could not be tested for statistical significance in the primary clinical trials due to the hierarchical outcome testing procedure.28,29
Knowledge Gaps & Future Developments
Enthesitis measurement remains an area of intense research. Although diagnosis and follow-up are largely clinical due to feasibility considerations, evidence exists that ultrasound and/or MRI assessments have the potential to more directly measure the pathophysiological changes induced by the PsA disease process.12
In clinical trials, only a portion of patients with dactylitis and/or enthesitis responded to the agents noted above. The numbers of new onset and recurrent dactylitis and enthesitis in clinical trials are of great relevance for clinical practice and treatment guidelines, but they are not commonly reported. None of these therapies have been compared in head-to-head analyses, and none have been specifically studied for enthesitis or dactylitis as primary efficacy endpoints. Studies using multiple methods of assessment that capitalize on independently capturing definite underlying pathology in enthesitis and dactylitis are needed to improve our evidence base for treating these PsA-specific manifestations.