title: Efficacy, safety and medication cost implications of adalimumab 40 mg weekly dosing in patients with psoriasis with suboptimal response to 40 mg every other week dosing: results from an open-label study.
abstract: BACKGROUND
  The clinical utility of increasing to weekly adalimumab therapy in patients with psoriasis with inadequate response to every other week (eow) dosing is unknown.
  
  
  OBJECTIVE
  (i) To determine the effectiveness of escalating adalimumab dosage from 40 mg eow to 40 mg weekly in patients with < PASI 50 response following ≥ 24 weeks treatment. (ii) To identify retrospectively characteristics of patients likely to benefit from dose escalation using classification and regression tree analysis. (iii) To assess cost implications for allowing dose escalation from the private payers' perspective.
  
  
  METHODS
  Patients with moderate-to-severe psoriasis who had received blinded adalimumab 40 mg eow or placebo in antecedent phase II/III studies could enrol in an open-label extension (OLE) and initially receive open-label adalimumab 40 mg eow (EOW population). On/after week 24 (OLE), patients with < PASI 50 response relative to baseline of antecedent study could increase to 40 mg weekly. The dosage escalation population continued on weekly dosing until achieving PASI 75 response, then resumed eow dosing. Study visits were 6/12 weeks after dosage escalation, and every 12 weeks thereafter. The percentage of patients who achieved PASI 75 response following dosage escalation was determined (missing PASI scores imputed as nonresponse). Safety was assessed for the dosage escalation population and for all adalimumab exposure that did not follow dosage escalation in the EOW set.
  
  
  RESULTS
  In total, 349/1256 (27·8%) patients underwent dosage escalation (OLE). At 12/24 weeks after dosage escalation, 93/349 (26·6%)/133/349 (38·1%) were PASI 75 responders or resumed eow dosing. Secondary nonresponders, patients weighing ≤ 102 kg, and those with disease duration < 8·3 years were most likely to benefit from dose escalation. Rates of serious/serious infectious/malignant (excluding nonmelanoma skin cancers or lymphoma) adverse events were 6·8/0·9/1·4 events per 100 patient-years (dosage escalation population); comparable rates in the EOW set were 6·5/1·2/0·5 events per 100 patient-years.
  
  
  CONCLUSIONS
  Most patients did not require dose escalation. By 12 weeks after dose escalation, one-quarter achieved substantial clinical improvement. Safety results were similar between patients who dosage-escalated and those who did not.
authors.affiliation: Central Dermatology, 1034 South Brentwood, Suite 600, St Louis, MO 63117, USA. leonardi@centralderm.com
authors.forename: C
authors.initials: C
authors.lastname: Leonardi
authors.forename: J M
authors.initials: JM
authors.lastname: Sobell
authors.forename: J J
authors.initials: JJ
authors.lastname: Crowley
authors.forename: U
authors.initials: U
authors.lastname: Mrowietz
authors.forename: Y
authors.initials: Y
authors.lastname: Bao
authors.forename: P M
authors.initials: PM
authors.lastname: Mulani
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: M M
authors.initials: MM
authors.lastname: Okun
mesh_terms: D000068879:Adalimumab; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016527:Drug Costs; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D011565:Psoriasis / Q000188:drug therapy* / Q000191:economics; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; D000068879:Adalimumab