Efficacy of tumor necrosis factor α blockade for enthesitis in spondylarthropathy: Comment on the article by Marzo-Ortega et al

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Efficacy of Tumor Necrosis Factor α Blockade for Enthesitis in Spondylarthropathy: Comment on the Article by Marzo-Ortega et al

To the Editor:

We read with great interest the article by Marzo-Ortega and coworkers on the efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthropathy (SpA) (1). Using magnetic resonance imaging (MRI), the authors demonstrated that tumor necrosis factor α (TNFα) blockade can induce marked improvement or regression of enthesitis and associated osteitis in both the axial skeleton and the peripheral skeleton. The following case presentation confirms their observations.

The patient is a 34-year-old man with HLA–B27–positive juvenile-onset undifferentiated SpA lacking axial involvement. In 1996, he had a severe, disabling, nonsteroidal antiinflammatory drug (NSAID)–resistant flare of the disease in his left knee and in the insertions of the Achilles tendon and plantar fascia (both sites), which was treated with sulfasalazine at a dosage of 3 gm/day. After 6 months of therapy, the daily dosage was reduced to 2 gm/day, and after 12 months sulfasalazine was discontinued. The disease remained in remission until August 2000, when the patient experienced severe pain in his right hip that was resistant to indomethacin at a dosage of 150 mg/day. Physical examinations performed on several occasions in the following months showed severe tenderness and limitation of motion of the right hip. There was also slight tenderness in the left hip.

On October 14, 2000, radiographs of the pelvis were normal, and laboratory evaluation showed a normal erythrocyte sedimentation rate and a C-reactive protein (CRP) value of 17.6 mg/liter (normal <5). MRI showed an increased signal on short tau inversion recovery images in both hips, extending from the right femoral head to the intertrochanteric region, caused by bone marrow edema (Figure 1A).

Figure 1.

Magnetic resonance imaging (MRI) of the hips. A, Short tau inversion recovery image showing increased signal extending from the right femoral head to the intertrochanteric region due to bone marrow edema. B, Repeat MRI, performed 8 weeks after the first examination and the beginning of infliximab therapy, showing dramatic improvement of bone edema at the right hip and regression at the left side.

Because of the severity of the clinical situation and the MRI findings, we decided to treat the patient with infliximab, after obtaining his informed consent. He received the drug at a dose of 5 mg/kg by intravenous infusion at 0, 2, and 6 weeks. He was evaluated at baseline, on days 3, 7, and 14, and then every 2 weeks. The day after the first infusion, the hip pain improved, and after 1 week the daily dose of indomethacin was reduced to 100 mg. On the day of the second infusion, CRP was normal, and hip pain was less severe. The dosage of indomethacin was reduced to 50 mg/day. On the day of the third infusion, the pain had disappeared, and indomethacin was discontinued. A repeat MRI, performed 8 weeks after the first examination and the beginning of infliximab therapy, showed a dramatic improvement of bone edema at the right hip and regression on the left side (Figure 1B). On T1-weighted images, with fat saturation obtained after the administration of intravenous gadolinium, there was low enhancement in the right femoral head and no enhancement in the left. To date, the disease has remained in remission, and the patient has taken no medication. A third MRI performed at month 6 was normal.

Both main biologic agents blocking TNFα, the chimeric monoclonal IgG1 antibody infliximab and the 75-kd IgG1 fusion protein etanercept, have been proven effective in both ankylosing spondylitis (2, 3) and psoriatic arthritis (3–6). Both agents can ameliorate the enthesitis-related bone edema that is visible on MRI (1, 7). Unresponsiveness of undifferentiated SpA to sulfasalazine is another possible indication for TNFα blockade therapy (8). We decided to use infliximab to treat our patient with undifferentiated SpA, because of the severity of hip pain and the impressive MRI findings showing enthesitis and osteitis involving the femoral head and neck. The appearance of enthesitis and osteitis on MRI was similar to that of idiopathic transient osteoporosis of the hip from which our case can be differentiated, especially based on the absence of localized osteoporosis on radiographs (9).

As suggested by Marzo-Ortega et al, bone edema caused by enthesitis and osteitis is the forerunner of severe destruction and new bone formation in SpA (1). The authors also suggested that by suppressing the diffuse osseous pathology, TNFα blockade may prevent destructive arthritis. In our case, infliximab may have prevented destructive hip arthritis. Future studies on a large number of similar cases will resolve this question.

Ignazio Olivieri MD*, Angela Padula MD*, Enrico Scarano MD†, * San Carlo Hospital of Potenza, and Madonna delle Grazie Hospital, Potenza and Matera, Italy, † San Carlo Hospital of Potenza, Potenza, Italy.

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