ROCHESTER, NY – The TNF inhibitors infliximab and etanercept are both effective for treatment of enthesopathy associated with psoriatic arthritis (PsA) and with spondyloarthropathies, but sulfasalazine is ineffective, methotrexate has not been studied, and the most widely used treatment modalities are unsupported by clinical evidence, according to a systematic literature review by Christopher T. Ritchlin that appears in the May 15, 2006, online edition of the Journal of Rheumatology.1

"Despite the almost universal recommendation in textbooks and review articles regarding the potential effectiveness of [NSAIDs, physiotherapy, and corticosteroid injections], controlled trials or case series that reported outcomes in SpA patients treated with any of these modalities could not be identified," Dr. Ritchlin writes.

"Psoriatic enthesopathy ... [is] quite often resistant to therapy with NSAIDs and other disease-modifying antirheumatic agents (DMARDs), but responsive to anti-TNF therapy."  —Christopher T. Ritchlin, MD
Enthesitis or inflammation at the tendon, ligament, and joint capsule sites or fascia insertion sites of bone is common in PsA. It typically manifests as plantar fascitis, epicondylitis, and Achilles tendonitis. Dr. Ritchlin set out to determine what therapies are effective for the treatment for enthesitis in PsA patients. An initial search looking for studies of a specific agent for enthesitis in PsA yielded only three articles, so the search terms were broadened to include ankylosing spondylitis (AS) and other forms of spondyloarthritis (SpA).

Dr. Ritchlin reports that comparing treatments is difficult because there are no validated outcome measures. Ultrasonography and magnetic resonance imaging (MRI) appear to be the most useful tools for monitoring disease activity and response to therapy, however. 

Treating the manifestations of psoriatic enthesopathy is more challenging than treating other causes of plantar fasciitis but is important, since PsA is estimated to cause about 30% of plantar fasciitis cases, Dr. Ritchlin told CIAOMed. He said it is important to differentiate this cause from other causes of heel pain because "psoriatic enthesopathy is often associated with arthritis in other joints and it can be refractory to traditional anti-inflammatory therapies." 

"Psoriatic enthesopathy can also stimulate bone loss and new bone formation, which can alter joint function, can be associated with significant pain and disability, and quite often is resistant to therapy with NSAIDs and other disease-modifying antirheumatic agents [DMARDs], but responsive to anti-TNF therapy," Dr. Ritchlin said.

In the absence of solid data, "[Treatment] really depends on the setting in each individual patient," Dr. Ritchlin told CIAOMed. "Enthesitis in the plantar fascia, Achilles tendons, or epicondyles are the most common and often very painful [and a] variety of modalities can help, including physiotherapy, NSAIDs, orthotics, and occasionally injections. Anti-TNF agents are reserved for patients with accompanying moderate-to-severe skin and/or joint disease, but they are very effective for enthesitis."

Treatment recommendations

The 10 studies found during the expanded literature search looked at several potential treatments for enthesitis. Dr. Ritchlin reported that sulfasalazine (SSZ) is not an effective treatment for enthesitis in PsA, according to three double-blind randomized placebo-controlled trials. In one such study by Daniel Clegg, MD, of the University of Utah School of Medicine in Salt Lake City,2 the modified Mander Enthesitis Index (MEI) score decreased in both the SSZ group and the placebo groups; however, the difference in change score was not significant, the study showed.

Mesalamine is effective at treating enthesitis in SpA, but the open-label design of the one trial3 cited cannot provide any definitive conclusions, Dr. Ritchlin reports. Methotrexate has not been studied in enthesitis in PsA enthesopathy.

Role for TNF blockade

The tumor necrosis factor-alpha (TNF-a) inhibitor infliximab can be effective in treating enthesitis in PSA, while etanercept is effective in treating enthesitis in SpA, Dr. Ritchlin writes.

"These recommendations should be viewed with caution, however, because the data underlying them are incomplete and in many cases severely flawed," Dr. Ritchlin writes. Many different outcome measures were used in the studies evaluating TNF-a inhibitors and none of them have been validated in PsA, he says.

Importantly, there are no trials on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, and intratendinous steroid injections, despite the fact that they are widely recommended by textbooks and review articles for the treatment of enthesitis in PsA.

"This does not mean that those therapies are ineffective," Dr. Ritchlin told CIAOMed. "We simply do not have good trial data supporting efficacy because the trials have not been performed."

Going forward, randomized controlled trials with DMARDs, which include enthesitis endpoints, are needed, he says, adding that the Group for Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is currently developing enthesitis instruments for clinical trials.

References

  1. Ritchlin CT. Therapies for psoriatic enthesopathy. A systematic review. J Rheumatol. 15 May 2006; [Epub ahead of print]
  2. Clegg DO, Reda, DJ, Mejias E, et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum. 1996;39:2013-2020.
  3. Thomson, GT, Thomson BR, Thomson KS, Ducharme JS. Clinical efficacy of mesalamine in the treatment of the spondyloarthropathies. J Rheumatol. 2000;27:714-718.