Cyclosporine for Ocular Inflammatory Diseases

Abstract

Purpose-To evaluate the clinical outcomes of cyclosporine treatment for non-infectious ocular inflammation Design-Retrospective cohort studyParticipants-Three hundred seventy-three patients with non-infectious ocular inflammation managed at four tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single non-corticosteroid immunosuppressive agent to their treatment regimen, between 1979-2007 inclusive. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Methods-Participants Precis:Within one year of cyclosporine therapy, about half of ocular inflammation patients achieved stable, complete inflammatory control, a minority achieved corticosteroid-sparing goals, and <10% successfully discontinued corticosteroids. Toxicity was frequent after 55 years of age. NIH Public Access Author ManuscriptOphthalmology. Author manuscript; available in PMC 2011 March 1. Published in final edited form as:Ophthalmology. and main outcome measures were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Main Outcome Measures: Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity.Results-Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by six months and 51.9% by one year gained sustained, complete control of inflammation over at least two visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone 10 mg/day or less) was achieved by 22.1% by six months and 36.1% within one year. Toxicity led to discontinuation of therapy within one year by 10.7% of the population. Patients over 55 years of age were over 3-fold more likely to discontinue therapy because of toxicity than patients ages 18-39 years. Doses of 151-250 mg/day tended to be more successful than lower doses, and were not associated with a higher discontinuation for toxicity rate; higher doses did not appear to offer a therapeutic advantage.Conclusion-Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151-250 mg/day. While cyclosporine was tolerated by the majority of patients, toxicity was much more frequent with increasing age; alternative agents may be preferred for patients over 55 years of age.Cyclosporine (Cyclosporine A) ...

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

“…Again, the US SITE cohort recently showed that 51.9% of cases achieved remission by 1 year, but only 36.1% of patients were able to reduce steroids to below 10 mg/day. 60 Contemporaneously, there have been developments in other T cell inhibitors acting via inhibition of calcineurin-dependent IL-2 transcription, including the use of tacrolimus. Such developments were timely because the adverse effects of CsA were increasingly apparent and highlighted again in the SITE study, which demonstrated a threefold increase in drug cessation due to intolerance in patients over 55 years of age.…”

Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices

“…Firstly, some diseases such as birdshot chorioretinopathy, juvenile idiopathic arthritis-uveitis and serpiginous choroiditis respond poorly to these medications, even with combination therapy at maximum therapeutic doses. 10 Secondary, even in most experienced tertiary centers, corticosteroid-sparing success (sustained control of inflammation while tapering prednisone to 10 mg or less among those not meeting success criteria initially) was gained by 60%-70% of patients with ocular inflammation for CTX 15 and AZA, 16 and by 36% for CsA, 17 The major concern of corticosteroids, however, is their ocular and systemic side effects of long-term use. 9 Generally initial high-dose oral corticosteroids are continued for no longer than 1 month before commencement of tapering, and long-term maintenance dosage should be less than 10 mg per day of prednisone or its equivalent.…”

Uveitis Treatment Trials—A Cross-study Perspective

“…Specifically, the Systemic Immunosuppression Therapy for Eye Disease (SITE) Study Group has now published long-term, retrospective, multicenter data on over 8500 patients with noninfectious ocular inflammatory disease, including uveitis, followed at selected tertiary referral centers in the United States. 16 The reports have summarized the investigators experience with 5 different immunosuppressive agents to-date: azathioprine, 17 methotrexate, 18 cyclophosphamide, 19 cyclosporine, 20 and mycophenolate mofetil. 21 Similarly, the Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group has recently published 24-month, randomized, multicenter trial data comparing systemic therapy (corticosteroids plus immunosuppression when indicated) to Bausch & Lomb's fluocinolone acetonide intravitreal implant, 0.59 mg (Retisert; implant therapy) for noninfectious intermediate, posterior, or panuveitis.…”

“…[28][29][30][31] Response rate trends from both the SITE Cohort Study reports and the Proctor study suggest similar, although perhaps less dramatic, 12-month improvements in controlling inflammation and corticosteroid sparing success when systemic immunosuppressive therapy was used. In addition, the SITE study data, derived from the same treatment centers using the same analytic approach, 16 suggest the intriguing possibilities, by no means substantiated statistically, that the modest success at controlling inflammation with cyclosporine 20 may have come at the cost of increased corticosteroid exposure, and that mycophenolate mofetil 21 may have been particularly effective at controlling inflammation by 12 months. Cyclophosphamide 19 also appeared to be effective at controlling inflammation, but in a different patient population and with what appeared to be more toxicities and a higher discontinuation rate relative to other agents.…”

“…Moreover, in patients who did achieve control, some required >10 mg/ day of prednisone or its equivalent to achieve that goal 1,[17][18][19][20][21] -this despite the generally held view by such specialists that an acceptable maintenance dose of oral prednisone is below 10 mg/day. 32 While the cause of such partial patient responses is clearly complex and undoubtedly includes incomplete individual responses to the specific agents and approaches used in the various studies, including relative resistance to corticosteroids, 33 perhaps we should all give more consideration to other less generally used options for treating patients with chronic sight-threatening uveitis, such as short-term, high-dose chlorambucil [34][35][36] and systemic interferon therapy, 37,38 both of which, like cyclophosphamide, appear to offer the possibility of drug-free remission.…”