title: The efficacy of sirolimus in the treatment of patients with refractory uveitis.
abstract: OBJECTIVE
  To determine the efficacy of sirolimus in the treatment of patients with severe non-infectious uveitis.
  
  
  METHODS
  Eight patients with severe non-infectious uveitis were recruited to an open study. Inclusion criteria were limited to patients whose disease was not controlled with at least two or more separate steroid sparing immunosuppressants (either because of unacceptable side effects or ineffectiveness of the drug) or who required regular doses of corticosteroids either as high dose systemic or orbital floor injections in order to control their disease. Intraocular inflammation, visual acuity, symptoms, corticosteroid burden, drug toxicity, and side effects were monitored.
  
  
  RESULTS
  Sirolimus therapy was effective in five of the eight patients, all of whom had their dose of corticosteroids reduced or discontinued. Treatment in three patients was considered a failure as it caused intolerable side effects and/or failed to control the uveitis. Side effects were common and were typically gastrointestinal or cutaneous in nature. The severity of symptoms was dose dependent in most cases and occurred at trough blood levels above 25 ng/ml.
  
  
  CONCLUSIONS
  Sirolimus is an effective and potent immunosuppressive treatment in the majority of patients with non-infectious uveitis and can reduce the need for long term supplementary corticosteroid therapy. Further studies are required to establish the long term efficacy and safety of sirolimus alone or in combination with other steroid sparing immunosuppressants.
authors.affiliation: Division of Ophthalmology and Visual Science, B Floor, Eye and ENT Centre, Queens Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: V A
authors.initials: VA
authors.lastname: Shanmuganathan
authors.forename: E M
authors.initials: EM
authors.lastname: Casely
authors.forename: D
authors.initials: D
authors.lastname: Raj
authors.forename: R J
authors.initials: RJ
authors.lastname: Powell
authors.forename: A
authors.initials: A
authors.lastname: Joseph
authors.forename: W M
authors.initials: WM
authors.lastname: Amoaku
authors.forename: H S
authors.initials: HS
authors.lastname: Dua
mesh_terms: D000328:Adult; D002908:Chronic Disease; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D012008:Recurrence; D012720:Severity of Illness Index; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy* / Q000503:physiopathology; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011239:Prednisolone; D020123:Sirolimus