title: Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.
abstract: OBJECTIVE
  To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis).
  
  
  METHODS
  Randomized controlled parallel superiority trial.
  
  
  METHODS
  Patients with active or recently active uveitis.
  
  
  METHODS
  Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis.
  
  
  METHODS
  Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life, ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked.
  
  
  RESULTS
  On evaluation of changes from baseline to 24 months among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), the implant and systemic therapy groups had an improvement in visual acuity of +6.0 and +3.2 letters (P = 0.16, 95% confidence interval on difference in improvement between groups, -1.2 to +6.7 letters, positive values favoring implant), an improvement in vision-related quality of life of +11.4 and +6.8 units (P = 0.043), a change in EuroQol-EQ5D health utility of +0.02 and -0.02 (P = 0.060), and residual active uveitis in 12% and 29% (P=0.001), respectively. Over the 24 month period, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio [HR] = 3.3, P < 0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001), and glaucoma (17%, HR=4.2, P = 0.0008). Patients assigned to systemic therapy had more prescription-requiring infections than patients assigned to implant therapy (0.60 vs 0.36/person-year, P=0.034), without notable long-term consequences; systemic adverse outcomes otherwise were unusual in both groups, with minimal differences between groups.
  
  
  CONCLUSIONS
  In each treatment group, mean visual acuity improved over 24 months, with neither approach superior to a degree detectable with the study's power. Therefore, the specific advantages and disadvantages identified should dictate selection between the alternative treatments in consideration of individual patients' particular circumstances. Systemic therapy with aggressive use of corticosteroid-sparing immunosuppression was well tolerated, suggesting that this approach is reasonably safe for local and systemic inflammatory disorders.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Ocular Inflammation Service, The University of Pennsylvania, Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Kempen
authors.forename: Michael M
authors.initials: MM
authors.lastname: Altaweel
authors.forename: Janet T
authors.initials: JT
authors.lastname: Holbrook
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Jabs
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Louis
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sugar
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Thorne
mesh_terms: D004343:Drug Implants; D004359:Drug Therapy, Combination; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage*; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008269:Macular Edema / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015864:Panuveitis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011241:Prednisone / Q000008:administration & dosage*; D011788:Quality of Life; D018434:Sickness Impact Profile; D016896:Treatment Outcome; D015867:Uveitis, Intermediate / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015866:Uveitis, Posterior / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: D004343:Drug Implants; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D005446:Fluocinolone Acetonide; D011241:Prednisone