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Some patients (20–30%) with spondyloarthropathies (SpA) have a persistent and disabling disease,1 for which a limited number of alternative therapeutic approaches exist.2 The successful results from randomised, double blind, placebo controlled trials in ankylosing spondylitis (AS) and SpA which have been published 3–5 suggest that treatment with infliximab is highly effective. However, in most of these studies, criteria for the selection of patients are based on active disease, but not on refractory disease (failure of response to previous drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs). Therefore, we aimed at assessing the effectiveness and safety of infliximab in patients with active and refractory SpA.
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.
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.
We are indebted to Schering-Plough (Spain) and Centocor for the supply of the drug. We thank Dr Elisa Muñoz for statistical assistance.
The authors are members of the Spanish Spondyloarthropathy Study Group
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