Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial.
Abstract | IMPORTANCE: Orbital inflammation is a potentially blinding and disfiguring disease process that is often treated with systemic corticosteroids and immunosuppression; better treatments are needed. OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: A dose-ranging, randomized, double-masked phase 1/2 clinical trial was conducted at a tertiary referral ophthalmology clinic. Ten individuals with orbital inflammation refractory to systemic corticosteroids and at least 1 other immunosuppressive agent were enrolled from January 2007 to March 2010. INTERVENTIONS:
Rituximab infusions were administered on study days 1 and 15 at doses of either 500 mg or 1000 mg. Initial responders with recurrent inflammation after week 24 were permitted reinfusion with an additional cycle of 2 open-label 1000-mg rituximab infusions. MAIN OUTCOMES AND MEASURES: RESULTS: Of 10 enrolled patients, 7 demonstrated improvement on the orbital disease grading scale at the 24-week end point with rituximab therapy. Of these 7 individuals, 4 were receiving corticosteroids at study inception and all achieved successful dose reduction. For the secondary outcome measures in the 10 participants, 7 patients and 8 patients improved in self-rated and physician global health scores, respectively, and 7 patients had reduction in pain by 25% or more at 24 weeks. Four patients who were positive responders at the week 24 end point experienced breakthrough inflammation after week 24 and received reinfusions between 24 and 48 weeks. Vision remained stable in all participants. Three of 10 patients had short-term objective or subjective worsening 2 to 8 weeks after receiving rituximab infusions, which was averted in subsequent patients with oral corticosteroids administered during the infusion and did not affect the eventual positive treatment outcome. No significant differences with regard to efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. CONCLUSIONS AND RELEVANCE: TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00415506.
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Authors | Eric B Suhler, Lyndell L Lim, Robert M Beardsley, Tracy R Giles, Sirichai Pasadhika, Shelly T Lee, Alexandre de Saint Sardos, Nicholas J Butler, Justine R Smith, James T Rosenbaum |
Journal | JAMA ophthalmology
(JAMA Ophthalmol)
Vol. 132
Issue 5
Pg. 572-8
(May 2014)
ISSN: 2168-6173 [Electronic] United States |
PMID | 24652467
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD20
- Immunologic Factors
- Rituximab
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Murine-Derived
(administration & dosage)
- Antigens, CD20
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Follow-Up Studies
- Humans
- Immunologic Factors
(administration & dosage)
- Infusions, Intravenous
- Male
- Middle Aged
- Orbital Pseudotumor
(drug therapy, pathology)
- Recurrence
- Retrospective Studies
- Rituximab
- Severity of Illness Index
- Time Factors
- Treatment Outcome
- Visual Acuity
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