efficacy and safety of risedronate (actonel), a third generation bisphosphonate in patients with ankylosing spondylitis: a phase 2 pilot study

Conditions: Ankylosing Spondylitis

Summary: randomized, controlled, double-blind, multicenter phase ii study comparing risedronate 35mg (actonelr 35mg weekly tablet) versus placebo in patients with active ankylosing spondylitis (as) treated with standard first and second-line therapies. primary efficacy endpoint: bath ankylosing spondylitis disease activity index (basdai). the time schedule for performing the basdai was at screening, upon inclusion (t0), then after 3, 6 and 12 months or at the time of premature withdrawal in case of drop-out. secondary endpoints: * clinical endpoints: the secondary efficacy measures were the following: bath ankylosing spondylitis functional index (basfi) , bath ankylosing spondylitis metrology index (basmi), asas (assessments in ankylosing spondylitis) working group core set of domains, spinal pain vas, esr, crp and the percentage of patients achieving 20% or greater decrease in each of these parameters. these parameters were determined at t0, t3, t6, t12 or at the time of premature withdrawal in case of drop-out. the spinal pain assessed by vas was also done at screening. * dexa: dual energy x-ray-absorptiometry (dexa) measurements were performed in all patients upon inclusion (t0) and at the end of the study (t12). * biochemical markers: selected biochemical markers of bone metabolism were measured at t0, t3, t6 and t12 or at the time of premature withdrawal in case of drop-out using commercially available kits. bone formation was assessed by serum bone-specific alkaline phosphatase (bap) and osteocalcin (oc) levels using commercially available kits. bone resorption was assessed in serum by the c-terminal telopeptide of type i collagen degradation (crosslaps r) and urinary n-terminal telopeptide of type i collagen degradation (osteomark r). * trial with medicinal product


Eligibility criteria:
inclusion criteria: •male or non-pregnant women (only women who are post menopausal, surgically sterile or practicing a reliable method of contraception may be included) aged 20 years or more * meeting the modified new york diagnostic criteria for as (van der linden s et al., 1984) * symptoms of active as for more than 6 months prior to study entry * treated by first-line therapy (nsaids) for more than 6 months prior to study entry * bath as disease activity index (basdai) score of 4 or greater (garrett s et al, 1994) and * spinal pain of 4 or greater on a 10-cm visual analogue scale despite maximum recommended or tolerated doses of nsaids given for a minimum of 1 month prior to study entry exclusion criteria: •end-stage as with diffuse involvement of the spine (complete ankylosis) * intraarticular corticosteroid injections or iv infusion with methylprednisolone within the past 2 months prior to study entry. patients with ia corticosteroid injections of the sacroiliac joints within the past 9 months prior to study entry. * severe renal insufficiency: serum creatinine \> 25% above the upper limit of normal (\>177 umol/l) * hypocalcemia * major surgery within the past 3 months prior to study entry or planned in the ensuing 12 months * orthopaedic surgery within the last 12 months * severe infections or comorbidities, or active peptic ulcer disease * patients who received bisphosphonates in the past 12 months prior to study entry or patients having known allergies to bisphosphonates. * patients treated with anti-osteoporotic drugs (except: calcium and vit. d) in the past 12 months prior to study entry. * patients unable to remain in an upright position (sitting or standing) during a minimum of 30 minutes * no written informed consent obtained or inability to collaborate to the study design.