PATIENTS AND METHODS

The study was an open label, multicentre, 38 week prospective study in 40 patients with active and refractory SpA: 34 patients had AS, 3 had arthritis with related inflammatory bowel disease, and 3 undifferentiated SpA. Infliximab (5 mg/kg) was given at weeks 0, 2, 6, 14, 22, and 30. Patients were included according to the criteria of the European Spondyloarthropathy Study Group and/or Amor’s criteria for SpA. At the time of inclusion, all patients had active and refractory disease, defined as no satisfactory response to full doses of at least three different NSAIDs⁶ and/or no response to sulfazalazine in a minimum daily dose of 2 g for at least three months or to methotrexate at a minimum dose of 15 mg/week for at least two months.

Clinical evaluations were carried out at all visits (before the infusion) and at week 38. We evaluated: the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), patient global assessment of disease status, patient pain assessment, inflammation (represented by the mean of the two morning stiffness related BASDAI visual analogue scale scores), health related assessment of quality of life using the short form (SF-36) method,⁷ chest expansion, modified Schober, fingers to floor and occiput to wall tests. The primary outcomes variables were 50% improvement of disease activity (BASDAI 50%) between baseline and weeks 14 (after three infusions) and 38 (after six infusions). All our patients had axial involvement (alone or associated with the peripheral form), so we also used end points proposed by the Assessments in AS (ASAS) Working Group.⁸ Latent tuberculosis infection was investigated in all patients before study entry by a tuberculin test and chest radiographs.

RESULTS AND DISCUSSION

Thirty two men and eight women (mean age 41 years and mean disease duration 16 years) were studied. Eighteen patients had axial disease alone and 22 had axial and peripheral disease (mixed form). Table 1 shows the results of the variables evaluated at each visit. A significant and rapid improvement (after the first evaluation) was seen in all the variables analysed, except for occiput to wall test, and remained until week 38 (table 1). Increased values were seen in SF-36 measures that reached statistical significance in all domains (p<0.001).

A reduction in BASDAI of 50% or more compared with baseline was achieved in 24 patients (60%; 95% confidence interval (CI) 43% to 75%) at week 14 and in 21 patients (52.5%; 95% CI 36% to 68%) at week 38 (fig 1A). When response to treatment was analysed according to ASAS criteria (fig 1B): a 20% improvement was observed in 28 patients (70%; 95% CI 53% to 83%) at week 14 and in 24 patients (60%; 95%CI 25% to 57%) at week 38; 5 patients (12.5%; 95% CI 4% to 27%) achieved partial remission at weeks 14 and 38. Improvement was similar in the patients with axial disease alone and in those with mixed forms.

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Figure 1

Measured by the Bath Ankylosing Spondylitis Disease Activity Index on the 50% improvement level (BASDAI; fig 1A) and by criteria of ankylosing spondylitis working group for 20% improvement and partial remission (ASAS; fig 1B). No significant differences were detected between weeks 14 and 38 by the McNemar test.

Five adverse events were reported during the study: two patients had increased transaminase serum levels (one of them with persistently high levels was withdrawn from the study); one patient had an infectious prostatitis (re-entered into the study after antibiotic treatment and recovery); one transient anaphylactoid reaction (withdrawn), and another had a chorioretinitis (withdrawn). Thirty seven patients completed the 38 week follow up.

In conclusion, the results of this open prospective trial clearly indicate that infliximab is an effective therapeutic option for patients with refractory SpA.