title: Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease.
abstract: OBJECTIVE
  Steroids are often used as medical therapy for active thyroid eye disease (TED). While high-dose steroids have been shown to be effective in reducing the severity of TED symptoms, the side effects of steroids can be severe. As the pathogenesis of TED is thought to involve the upregulation of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), it has been postulated that anti-TNF agents may be used as steroid-sparing agents in the treatment of TED. This retrospective study was conducted to examine the efficacy of adalimumab, a subcutaneously administered TNF-α antagonist, in treating the inflammatory symptoms of active TED.
  
  
  METHODS
  All patients in the inflammatory phase of TED who were treated with adalimumab at the Jules Stein Eye Institute over a 2-year period were reviewed. Data concerning visual acuity, optic nerve function, extraocular motility restriction, binocular visual fields, and proptosis were extracted from patient charts. Clinical photographs from baseline and 3-month follow-up visits were reviewed by masked orbital specialists. Each photograph was graded on the severity of conjunctival injection, chemosis, eyelid erythema, and eyelid edema on a scale from 1 to 4. An inflammatory score was calculated as the sum of these 4 elements. Groups were compared using paired t tests.
  
  
  RESULTS
  Six of 10 patients showed a decrease in inflammatory score while on adalimumab, whereas 3 showed an increase and 1 stayed the same. One patient experienced a significant complication (hospital admission for sepsis). Eight patients received concomitant tapering steroids during the first 6 weeks of therapy as the adalimumab reached maximum efficacy. When data from all 10 subjects were analyzed together, there was no significant change in inflammatory index after 3 months of treatment with adalimumab. However, when the 5 patients with a high baseline inflammatory index (>4) were considered separately, there was a significant improvement (mean decrease of 5.2±2.7; p<0.01) after adalimumab treatment. Four of 5 patients also reported a subjective improvement in symptoms while on adalimumab.
  
  
  CONCLUSIONS
  This study suggests that adalimumab may have a role in the treatment of active TED with prominent inflammatory symptoms. The use of adalimumab and other immunosuppressive agents in the treatment of TED may help to mitigate some of the metabolic and psychiatric side effects of pulsed steroid treatment. A future randomized controlled study will be necessary to determine the efficacy of adalimumab as a primary therapy for TED.
authors: *Division of Orbital and Ophthalmic Plastic Surgery, Jules Stein Eye Institute; †David Geffen School of Medicine; and ‡Department of Medicine, Division of Rheumatology, University of California, Los Angeles, U.S.A.
authors: Reed
authors: R
authors: Ayabe
authors: Dan B
authors: DB
authors: Rootman
authors: Catherine J
authors: CJ
authors: Hwang
authors: Ami
authors: A
authors: Ben-Artzi
authors: Robert
authors: R
authors: Goldberg
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D005133:Eye Movements / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009900:Optic Nerve / Q000502:physiology; D054517:Orbital Cellulitis / Q000188:drug therapy* / Q000503:physiopathology; D055622:Orbital Myositis / Q000188:drug therapy* / Q000503:physiopathology; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab