title: Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of an oral phosphodiesterase 4 inhibitor, apremilast, in treatment of ankylosing spondylitis (AS) by monitoring symptoms and signs in a pilot study including exploratory investigation of effects of PDE4 inhibition on blood biomarkers of bone biology.
  
  
  METHODS
  In this double-blind, placebo-controlled, single-centre, Phase II study, patients with symptomatic AS with active disease on MRI were randomised to apremilast 30 mg BID or placebo over 12 weeks. Bath Indices were monitored serially. Patients were followed for 4 weeks after stopping medication. Bone biomarkers were assessed at baseline and day 85.
  
  
  RESULTS
  38 subjects were randomised and 36 subjects completed the study. Although the primary end-point (change in BASDAI at week 12) was not met, apremilast was associated with numerically greater improvement from baseline for all clinical assessments compared with placebo with mean change in BASDAI (-1.59±1.48 vs -0.77±1.47), BASFI (-1.74±1.91 vs -0.28±1.61) and BASMI (-0.51±1.02 vs -0.21±0.67); however, differences did not achieve statistical significance. The clinical indices returned to baseline values by 4 weeks after cessation of apremilast. Six apremilast patients (35.3%) vs 3 placebo (15.8%) achieved ASAS20 responses (p=0.25). There were statistically significant decreases in serum RANKL and RANKL:osteoprotegrin ratio and plasma sclerostin but no significant changes in serum DKK-1, bone alkaline phosphatase, TRAP5b, MMP3, osteoprotegrin, or osteocalcin.
  
  
  CONCLUSIONS
  Although a small pilot study, these results suggest that apremilast may be effective and well tolerated in AS and modulates biomarkers of bone biology. These data support further research of apremilast in axial inflammation.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors.forename: Ejaz
authors.initials: E
authors.lastname: Pathan
authors.forename: Sonya
authors.initials: S
authors.lastname: Abraham
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Van Rossen
authors.forename: Robin
authors.initials: R
authors.lastname: Withrington
authors.forename: Andrew
authors.initials: A
authors.lastname: Keat
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Charles
authors.forename: Erin
authors.initials: E
authors.lastname: Paterson
authors.forename: Muslima
authors.initials: M
authors.lastname: Chowdhury
authors.forename: Catherine
authors.initials: C
authors.lastname: McClinton
authors.forename: Peter C
authors.initials: PC
authors.lastname: Taylor
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005819:Genetic Markers; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D053245:RANK Ligand / Q000097:blood; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D053244:Osteoprotegerin; D058988:Phosphodiesterase 4 Inhibitors; D053245:RANK Ligand; C422903:SOST protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D013792:Thalidomide; C505730:apremilast