Rituximab therapy for refractory orbital inflammation results of a phase 1/2, dose-ranging, randomized clinical trial

Eric 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 (Jim) Rosenbaum

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Abstract

OBJECTIVE To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation. 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 The primary outcomeswere reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least 50%. The secondary outcomes were visual acuity, reduction in pain, and participantand physician-reported global health assessment. 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, 4were 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 subjectiveworsening 2 to 8weeks after receiving rituximab infusions, whichwas 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 Rituximab was safe and effective in 7 of 10 patients with noninfectious orbital disease, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Substantial toxicity was not noted. Rituximab should be considered in the treatment of refractory orbital inflammation.

Original languageEnglish (US)
Pages (from-to)572-578
Number of pages7
JournalJAMA Ophthalmology
Volume132
Issue number5
DOIs
StatePublished - 2014

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Randomized Controlled Trials
Inflammation
Orbital Diseases
Adrenal Cortex Hormones
Therapeutics
CD20 Antigens
Physicians
Pain
Clinical Trials, Phase I
Retreatment
Rituximab
Ophthalmology
Immunosuppressive Agents
Visual Acuity
B-Lymphocytes
Referral and Consultation
Monoclonal Antibodies
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Rituximab therapy for refractory orbital inflammation results of a phase 1/2, dose-ranging, randomized clinical trial. / Suhler, Eric; Lim, Lyndell L.; Beardsley, Robert M.; Giles, Tracy R.; Pasadhika, Sirichai; Lee, Shelly T.; De Saint Sardos, Alexandre; Butler, Nicholas J.; Smith, Justine R.; Rosenbaum, James (Jim).

In: JAMA Ophthalmology, Vol. 132, No. 5, 2014, p. 572-578.

Research output: Contribution to journalArticle

Suhler, E, Lim, LL, Beardsley, RM, Giles, TR, Pasadhika, S, Lee, ST, De Saint Sardos, A, Butler, NJ, Smith, JR & Rosenbaum, JJ 2014, 'Rituximab therapy for refractory orbital inflammation results of a phase 1/2, dose-ranging, randomized clinical trial', JAMA Ophthalmology, vol. 132, no. 5, pp. 572-578. https://doi.org/10.1001/jamaophthalmol.2013.8179
Suhler, Eric ; Lim, Lyndell L. ; Beardsley, Robert M. ; Giles, Tracy R. ; Pasadhika, Sirichai ; Lee, Shelly T. ; De Saint Sardos, Alexandre ; Butler, Nicholas J. ; Smith, Justine R. ; Rosenbaum, James (Jim). / Rituximab therapy for refractory orbital inflammation results of a phase 1/2, dose-ranging, randomized clinical trial. In: JAMA Ophthalmology. 2014 ; Vol. 132, No. 5. pp. 572-578.
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abstract = "OBJECTIVE To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation. 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 The primary outcomeswere reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least 50{\%}. The secondary outcomes were visual acuity, reduction in pain, and participantand physician-reported global health assessment. 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, 4were 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 subjectiveworsening 2 to 8weeks after receiving rituximab infusions, whichwas 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 Rituximab was safe and effective in 7 of 10 patients with noninfectious orbital disease, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Substantial toxicity was not noted. Rituximab should be considered in the treatment of refractory orbital inflammation.",
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T1 - Rituximab therapy for refractory orbital inflammation results of a phase 1/2, dose-ranging, randomized clinical trial

AU - Suhler, Eric

AU - Lim, Lyndell L.

AU - Beardsley, Robert M.

AU - Giles, Tracy R.

AU - Pasadhika, Sirichai

AU - Lee, Shelly T.

AU - De Saint Sardos, Alexandre

AU - Butler, Nicholas J.

AU - Smith, Justine R.

AU - Rosenbaum, James (Jim)

PY - 2014

Y1 - 2014

N2 - OBJECTIVE To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation. 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 The primary outcomeswere reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least 50%. The secondary outcomes were visual acuity, reduction in pain, and participantand physician-reported global health assessment. 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, 4were 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 subjectiveworsening 2 to 8weeks after receiving rituximab infusions, whichwas 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 Rituximab was safe and effective in 7 of 10 patients with noninfectious orbital disease, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Substantial toxicity was not noted. Rituximab should be considered in the treatment of refractory orbital inflammation.

AB - OBJECTIVE To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation. 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 The primary outcomeswere reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least 50%. The secondary outcomes were visual acuity, reduction in pain, and participantand physician-reported global health assessment. 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, 4were 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 subjectiveworsening 2 to 8weeks after receiving rituximab infusions, whichwas 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 Rituximab was safe and effective in 7 of 10 patients with noninfectious orbital disease, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Substantial toxicity was not noted. Rituximab should be considered in the treatment of refractory orbital inflammation.

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