Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease

Ophthalmic Plast Reconstr Surg. 2014 Sep-Oct;30(5):415-9. doi: 10.1097/IOP.0000000000000211.

Abstract

Purpose: 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.

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Eye Movements / physiology
  • Female
  • Glucocorticoids / therapeutic use
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / physiopathology
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Optic Nerve / physiology
  • Orbital Cellulitis / drug therapy*
  • Orbital Cellulitis / physiopathology
  • Orbital Myositis / drug therapy*
  • Orbital Myositis / physiopathology
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Visual Acuity / physiology
  • Visual Fields / physiology

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Glucocorticoids
  • Tumor Necrosis Factor-alpha
  • Adalimumab