title: Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS).
abstract: OBJECTIVE
  To evaluate efficacy and safety of ustekinumab in patients with ankylosing spondylitis (AS).
  
  
  METHODS
  In this prospective, open-label, single-arm, proof-of-concept clinical trial (ClinicalTrials.gov identifier NCT01330901), ustekinumab in a dose of 90 mg was administered subcutaneously at baseline, week 4 and week 16 in 20 patients with active AS. Eligible patients were required to have a diagnosis of AS according to the modified New York criteria and an active disease defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4 despite previous non-steroidal anti-inflammatory drug (NSAID) treatment. The primary study endpoint was the proportion of patients reached the Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 24.
  
  
  RESULTS
  At week 24, ASAS40 response was reached by 65% of the patients. ASAS20, ASAS5/6 and ASAS partial remission were observed in 75%, 50% and 30% of the patients, respectively. A ≥50% improvement of the BASDAI (BASDAI50) occurred in 55% of the patients. A total of 50% and 20% of the patients achieved the AS Disease Activity Score (ASDAS) clinically important improvement and major improvement, respectively. At week 24, 35% of the patients had an ASDAS inactive disease (ASDAS <1.3). Significant improvement of other patient-reported outcome parameters and active inflammation as detected by MRI as well as significant reduction of NSAIDs intake occurred during the treatment. Clinical response correlated with reduction of active inflammation on MRI and of serum C reactive protein level. Overall, ustekinumab was well tolerated.
  
  
  CONCLUSIONS
  In this prospective, open-label, proof-of-concept clinical trial, ustekinumab treatment was associated with a reduction of signs and symptoms in active AS and was well tolerated.
authors.affiliation: Rheumatology, Med. Department I, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, , Berlin, Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Poddubnyy
authors.forename: Kay-Geert A
authors.initials: KG
authors.lastname: Hermann
authors.forename: Johanna
authors.initials: J
authors.lastname: Callhoff
authors.forename: Joachim
authors.initials: J
authors.lastname: Listing
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D000069549:Ustekinumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069549:Ustekinumab
keywords: Ankylosing Spondylitis; Spondyloarthritis; Treatment