Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis

Objective. To develop criteria for symptomatic improvement in patients with ankylosing spondylitis (AS), using outcome domain data from placebo-contro lled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs). Methods. Patient data from 5 short-term, randomized, controlled trials were used to assess equivalence, reliability, and responsiveness of multiple it ems in the 5 outcome domains for AS treatment: physical function, pain, spi nal mobility, patient global assessment, and inflammation. At least one mea sure per domain was responsive (standardized response mean of >0.5), except for the spinal mobility domain, which was omitted from the criteria. We de veloped and tested candidate improvement criteria in a random two-thirds su bset from the 3 largest trials and used the remaining one-third for validat ion. These 3 largest trials included 923 patients (631 receiving NSAIDs, 29 2 in placebo groups). We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of less than or equal to 25%. Results. Candidate definitions were changes in single domains and in multip le measure indices, as well as combinations of improvements in multiple dom ains. Worsening in a domain was defined as a change for the worse of greate r than or equal to 20% and a net change for the worse of greater than or eq ual to 10 units on a scale of 0-100. Partial remission (for comparison purp oses) was defined as an end-of-trial value of <20/100 in each of the 4 doma ins. Among 20 candidate criteria, change of <greater than or equal to>20% a nd greater than or equal to 10 units in each of 3 domains and absence of wo rsening in the fourth discriminated best in the development subset (51% of patients improved with NSAIDs, 25% with placebo; chi (2) = 36.4, P < 0.001) . Results were confirmed in the validation subset. Almost all patients sati sfying the definition of partial disease remission at the end of the trial had also improved by this criterion. Among all 923 patients, improvement ra tes using this criterion were 49% for NSAID-treated patients and 24% for pl acebo-treated patients. Conclusion. Although further validation using data from new trials is still needed, we conclude that we have developed a clinically valid, easy-to-use measure of short-term improvement in AS.