Ankylosing spondylitis: What is the optimum duration of a clinical study? A one year versus a 6 weeks non-steroidal anti-inflammatory drug trial

Abstract

Objective. To consider the relevance of the duration of a clinical trial in ankylosing spondylitis: long-term (i.e. 1 yr) vs short-term (i.e. 6 weeks) assessment of a non-steroidal antiinflammatory drug (NSAID)-placebo controlled study. Methods. The design was a prospective, multicentre, double-blind, placebo-controlled study of 6 weeks duration with a 12 months double-blind extension. Study drugs were placebo (n = 121) or active NSAID (n = 352). A decrease of at least 50% in pain and/or global assessment and/or functional impairment during the study defined the response to treatment. The percentage of patients discontinuing the study drug over time (life table analysis) permitted the evaluation of both the efficacy and toxicity. Results. Among the 473 recruited patients, the percentage of responders was similar at 1 yr and week 6 with a highly statistically significant difference in favour of the active NSAID groups when compared to placebo (at 1 yr, 17% in the placebo group vs 37, 50 and 43% in the piroxicam 20 mg, meloxicam 15 mg and meloxicam 22.5 mg, respectively, for the patient's overall assessment) without any statistically significant difference between the three active groups. However, evaluation of the patients discontinuing the study drug during the 1 yr of the study permitted the detection of a statistically significant difference between the active NSAID groups. A lower percentage of patients taking meloxicam 22.5 mg had to discontinue the study drug when compared to either meloxicam 15 mg or piroxicam 20 mg (37% vs 53% and 53%, respectively, P < 0.05). By 52 weeks, drug-related upper gastrointestinal adverse events occurred in 13, 32, 20 and 18% in the placebo, piroxicam 20 mg, meloxicam 15 mg and meloxicam 22.5 mg groups, respectively. Some of the adverse events occurred only after week 6. Conclusion. This study suggests that a 1 yr trial might be of optimum value compared to a 6 week assessment in order to define better the efficacy and tolerability of NSAIDs in ankylosing spondylitis.