Abstract | OBJECTIVE: DESIGN: Prospective, dose-ranging, randomized, double-masked phase I/II clinical trial. PARTICIPANTS: INTERVENTION: Subjects were randomly assigned to 500 (n = 5) or 1000 mg (n = 7) dosing arms of rituximab intravenous infusions (500 or 1000 mg), given at study days 1 and 15. Initial responders with breakthrough inflammation after study week 24 were offered treatment with an additional cycle of 2 open-label rituximab 1000 mg infusions. MAIN OUTCOME MEASURES: Primary outcomes were reduction of inflammation, as measured with a validated scleritis disease grading scale (SGS) and reduction in corticosteroid dose by ≥50%. Patients were characterized as responders to study therapy if ≥1 of these endpoints showed improvement and neither showed evidence of worsening. Secondary outcomes were improvement in visual acuity, reduction in pain, and improvement in patient and physician-reported global health assessment. RESULTS: Of 12 enrolled patients, 9 met the SGS endpoint at or before week 24, and 4 additionally were able to reduce corticosteroid dose by ≥50%. With regard to secondary outcome measures, 11 and 9 patients showed improvement in patient and physician global health scores, respectively, and 7 patients had reduction in pain. Of 9 initial responders, 7 experienced breakthrough inflammation after 24 weeks and were treated with a second cycle of rituximab infusions. Four patients had significant objective or subjective worsening within 8 weeks of receiving rituximab; this event was averted in subsequent patients by treatment with peri-infusional oral corticosteroid. No other significant adverse events were noted. No differences in efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. CONCLUSIONS:
Rituximab was effective treatment for 9 of 12 enrolled patients with refractory, noninfectious scleritis at 24 weeks, although 7 required reinfusion with rituximab to maintain inflammatory control. The treatment was well-tolerated, and peri-infusional inflammatory exacerbations were managed successfully with oral corticosteroids. Further long-term studies are warranted to determine the safety and efficacy of rituximab in treating noninfectious scleritis and other ocular inflammatory diseases.
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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 | Ophthalmology
(Ophthalmology)
Vol. 121
Issue 10
Pg. 1885-91
(Oct 2014)
ISSN: 1549-4713 [Electronic] United States |
PMID | 24953794
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antibodies, Monoclonal, Murine-Derived
- Immunologic Factors
- Rituximab
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Topics |
- Adult
- Antibodies, Monoclonal, Murine-Derived
(administration & dosage)
- Dose-Response Relationship, Drug
- Female
- Humans
- Immunologic Factors
(administration & dosage)
- Infusions, Intravenous
- Male
- Middle Aged
- Prospective Studies
- Rituximab
- Scleritis
(drug therapy)
- Severity of Illness Index
- Young Adult
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