Tumor necrosis factor α (TNFα) antagonists have been the most significant advancement in the management of the spondylarthritides in the last few years. All 3 currently available anti-TNFα blockers (infliximab, etanercept, adalimumab) have been approved for treatment of ankylosing spondylitis (AS) and psoriatic arthritis on the basis of controlled trials (1–6). However, not all patients respond to these agents, and some who do respond develop side effects. Such patients, similar to patients with rheumatoid arthritis (7), can be switched to another anti-TNFα agent (8, 9). Recently, we reported our experience with 23 patients with AS who were successfully switched from infliximab to etanercept, confirming that, in case of failure with one anti-TNFα blocking agent, switching to another may be useful in the treatment of patients with spondylarthritis (SpA) (8).
Severe and therapy-resistant heel enthesitis is a challenging and complicated problem in SpA (10). Recently, some patients with heel enthesitis resistant to traditional therapy have been successfully treated with infliximab (11) or adalimumab (12). We report the recent case of a patient with SpA showing severe and refractory heel enthesitis who we treated by switching from adalimumab to etanercept.
A 50-year-old man presented to us in December 2003 with a severe and nonsteroidal antiinflammatory drug (NSAID)–resistant right plantar fasciitis that had begun 3 months earlier. His medical history revealed that the disease had begun a few months before, in August 2003, with buttock pain and inflammatory cervical pain. In September 2003, these symptoms disappeared spontaneously and a severe pain in the right heel developed that was resistant to adequate trials with 3 NSAIDs (diclofenac, nimesulide, and celecoxib) administered at different times. The patient's medical history was otherwise unremarkable. His family history revealed that his sister had AS.
Physical examination revealed only a severe tenderness at the insertion of the right plantar fascia. There was no limitation of spine movement or chest expansion. The only aspect of laboratory evaluation worthy of note was an erythrocyte sedimentation rate of 27 mm/hour. HLA typing was positive for the B27 antigen. Radiographs of the spine, pelvis, and feet were normal. Ultrasound of the right plantar fascia showed a mild thickening of the insertion.
A diagnosis of late-onset undifferentiated SpA (uSpA) was made (13). In the following months, we performed 2 local injections of steroids at the insertion of the right plantar fascia without any results. The patient was unable to walk without crutches.
In April 2004, after observing successful results in a similar patient treated with adalimumab (12), we decided to begin adalimumab therapy at a dosage of 40 mg every other week after obtaining the patient's informed consent. The same day, before the injection, we performed magnetic resonance imaging (MRI) of the patient's feet, which showed swelling of the right plantar fascia together with edema of the adjacent bone. The patient scored pain as 80 mm on a 100-mm visual analog scale. The day after the first injection, the pain score improved to 40 mm, and in the few days following the second injection the score further improved to 30 mm. Unfortunately, pain worsened abruptly at such a level that we were forced to anticipate the third injection by a week. Nevertheless, pain did not improve and the base of the fifth right metatarsal bone, the left plantar fascia, and the iliac crests were involved. In addition, the patient developed inflammatory swelling with pitting edema on the dorsum of the left foot, which has been described in late-onset uSpA (13). In June 2004, we obtained a new MRI of his feet, which showed that the findings observed 2 months before persisted (Figure 1A). The patient scored pain in his right plantar fascia at 80 mm and was taking nimesulide without any result. We decided to switch the patient to etanercept at a dosage of 25 mg twice a week, which has been shown to be effective in enthesitis (14). After 1 week there was a 50% improvement in the pain. Pain in his left plantar fascia and iliac crests and swelling over the dorsum of his left foot disappeared. Only a mild pain in his right plantar fascia and the base of the fifth metatarsal persisted, which responded to 1-week therapy with nimesulide.
A new MRI, performed in August 2004, showed a marked improvement in the findings observed 2 months before (Figure 1B). In the following months there was a gradual improvement in pain, which disappeared completely in January 2005. A new MRI obtained in February 2005 was negative (Figure 1C). At the beginning of April 2005, etanercept therapy was withdrawn due to the persistent absence of pain and the normalization of MRI. The patient has been well without any pain until now.
Our patient has late-onset uSpA evolving with a severe and refractory heel enthesitis. Amor et al consider enthesitis to be refractory to therapy only when it continues insistently for more than 2 years despite conventional treatment including NSAIDs, steroid injections, sulfasalazine, methotrexate, and radiotherapy (10). Braun and Sieper have recently recommended that 6 months is an adequate period to attempt every traditional treatment (15).
Severe and therapy-resistant heel enthesitis is a challenging and difficult problem in the SpA field (10). Recently, D'Agostino et al successfully treated 2 patients with longstanding refractory HLA–B27-associated heel enthesitis with infliximab (11). They documented the response to the therapy using ultrasound combined with power Doppler. We treated a similar patient with adalimumab and documented the positive results using MRI (12). Waiting for a marked improvement in the bone edema was crucial for interrupting the therapy without having the recurrence of the clinical symptoms of enthesitis. Similarly, in the present patient etanercept therapy was stopped only after the normalization of MRI.
This article only deals with one case. The possibility that enthesitis spontaneously remitted could be taken into account. However, this is highly unlikely considering the temporal sequence of the events.
In the October 2006 issue of Arthritis Care & Research (8), we reported our experience with patients with AS who were successfully treated by switching from infliximab to etanercept, suggesting that, in case of lack of efficacy with one anti-TNFα blocking agent, switching to another may be beneficial in the treatment of patients with AS.
Our patient with heel enthesitis responded partially and temporarily to adalimumab but was cured with etanercept, suggesting that, in case of failure of one anti-TNFα blocking agent, the switch to another may be successful in severe and refractory SpA heel enthesitis.
Dr. Olivieri had full access to all of the data in the study and takes responsibility for the integrity of the data.
Study design. Olivieri, Padula, D'Angelo, Cantini.
Acquisition of data. Olivieri, Scarano, Padula, D'Angelo, Cantini.
Analysis and interpretation of data. Olivieri, Scarano, Padula, D'Angelo, Cantini.