Immunosuppressive Drugs

Gery, I.; Nussenblatt, R. B.

doi:10.1007/978-3-642-69222-2_14

Cited by 3 publications

(5 citation statements)

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“…Chlorambucil was first created in the 1950s, and was primarily used for the treatment of malignant lymphoma [3]. Its role in the ophthalmic world came about in 1970 when Mamo and Azzam [34] first reported its use and efficacy for the treatment of ABD.…”

Section: History and Sourcementioning

confidence: 99%

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Corticosteroid-Sparing Agents: Conventional Systemic Immunosuppressants

Kruh

Foster²

2012

Developments in Ophthalmology

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The introduction of corticosteroids in the mid-20th century to control inflammatory eye disease revolutionized treatment practices. As long-term use of corticosteroids became the backbone of immunosuppressive therapy, it soon became evident that it was associated with significant morbidity to the patient. For this reason, other immunosuppressant agents were sought. Thereafter, the first generation of immunosuppressive agents were born. The main action of all such agents involves the inhibition of lymphoid proliferation. The agents can be further subdivided into the following categories based on their specific mechanism of action: alkylating (cyclophosphamide and chlorambucil), antimetabolite (methotrexate, mycophenolate mofetil and azathioprine), and antibiotic/calcineurin inhibitor (cyclosporine, tacrolimus and sirolimus). These immunomodulating agents serve as the foundation to modern corticosteroid-sparing immunosuppressive therapy. Many times, these agents are now even indicated as first-line therapy for the treatment of systemic inflammatory diseases with destructive ocular sequela, e.g. Behçet's disease and granulomatosis with polyangiitis (Wegener's). Choosing the most appropriate immunomodulatory agent to initiate therapy can often be difficult; a multifactorial approach in the decision-making process is essential. Special attention must be given to the patient's medical history, type and severity of inflammatory disease, social history, compliance, age, and sex. Oftentimes, it takes a joint effort between the ophthalmologist and multiple sub-specialists (rheumatology, oncology, and hematology) to administer and monitor these therapies. Even though each of these systemic immunosuppressive agents has its own array of potential side effects, with careful monitoring and titration of dosages, such potential side effects can be minimized or avoided altogether. Ultimately, these patients are afforded a much more favorable longterm outcome, free of the devastating effects of chronic corticosteroid use.

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Section: History and Sourcementioning

confidence: 99%

“…Cyclophosphamide granulomatosis with polyangiitis (Wegener's), polyarteritis nodosa, necrotizing scleritis, scleritis associated with rheumatoid arthritis or polychondritis, Mooren's ulcer, cicatricial pemphigoid, sympathetic ophthalmia, ABD when its application for the treatment of uveitis was first reported by Roda-Perez [3][4][5].…”

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Corticosteroid-Sparing Agents: Conventional Systemic Immunosuppressants

Kruh

Foster²

2012

Developments in Ophthalmology

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“…This leads to cross-linking of DNA bases, abnormal base pairing, or DNA strand breakage, damaging cells when they undergo mitosis. This action profoundly suppresses the function of both T cells and B cells, broadly inhibiting the immune system 5, 6. Cyclophosphamide can be administered both orally (1-2mg/kg/day) and intravenously (750mg-1g/m 2 body surface area every 3 to 4 weeks) 5…”

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Cyclophosphamide for Ocular Inflammatory Diseases

et al. 2010

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Purpose-To evaluate the outcomes of cyclophosphamide therapy for non-infectious ocular inflammation. Design-Retrospective cohort studyParticipants-Two hundred fifteen patients with non-infectious ocular inflammation observed from initiation of cyclophosphamide.Methods-Patients initiating cyclophosphamide, without other immunosuppressive drugs (other than corticosteroids), were identified at four centers. Dose of cyclophosphamide, response to therapy, corticosteroid-sparing effects, frequency of discontinuation and reasons for discontinuation were obtained by medical record review of every visit.Main Outcome Measures-Control of inflammation, corticosteroid-sparing effects, discontinuation of therapy. 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. NIH Public Access Author ManuscriptOphthalmology. Author manuscript; available in PMC 2011 February 1. Published in final edited form as:Ophthalmology. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults-The 215 patients (381 involved eyes) meeting eligibility criteria carried diagnoses of uveitis (20.4%), scleritis (22.3%), ocular mucous membrane pemphigoid (45.6%) or other forms of ocular inflammation (11.6%). Overall, approximately 49.2% (95% confidence interval (CI): 41.7%-57.2%) gained sustained control of inflammation (for at least 28 days) within 6 months, and 76% (95% CI: 68.3%-83.7%) within 12 months. 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 30.0% and 61.2% by six and 12 months respectively. Disease remission leading to discontinuation of cyclophosphamide occurred at the rate of 0.32/person-year (95% CI: 0.24 -0.41), and the estimated proportion with remission at or prior to 2 years was 63.1% (95% CI: 51.5%-74.8%). Cyclophosphamide was discontinued by 33.5% of patients within one year because of side effects-usually of a reversible nature.Conclusions-Our data suggest that cyclophosphamide is effective for the majority of patients for controlling inflammation and allowing tapering of systemic corticosteroids to 10 mg of prednisone or less, although a year of therapy may be needed to achieve these goals. Unlike with most other immunosuppressive drugs, disease remission was induced by treatment in the majority of patients who were able to tolerate therapy. In order to titrate therapy properly and to minimize the risk of serious potential side effects, a systematic program of laboratory monitoring is required. Judicious use of cyclophosphamide appears bene...

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“…Chlorambucil, created in the 1950s, was originally used for the treatment of malignant lymphoma [14]. Its first reported use in the ophthalmic world was in 1970, when Mamo and Azzam utilized the drug for the treatment of the uveitis associated with Adamantiades-Behçet's disease [17].…”

mentioning

confidence: 99%

“…Its therapeutic efficacy lies in its ability to suppress the bone marrow, causing leukopenia and aplasia of lymphoid tissue [13]. Its first reported use in the 1950s was for the treatment of uveitis by Roda-Perez [14][15][16].…”

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The Philosophy of Treatment of Uveitis: Past, Present and Future

Kruh

Foster²

2012

Developments in Ophthalmology

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Treatment of inflammatory diseases of the eye is especially challenging. Although physicians in antiquity had recognized the existence of ocular inflammatory disease, their lack of understanding of the immune system made successful treatment almost impossible. Throughout the 20th century, great advances in the diagnosis and treatment of uveitis led to unique treatment options. The development of corticosteroids in 1949 and its application to the eye in 1950 revolutionized therapeutic strategies. As the use of corticosteroids became more prevalent in treating ocular inflammatory diseases, so did its side effects. Due to the high morbidity in conjunction with long-term corticosteroid use, physicians pursued other agents, specifically through the employment of chemotherapeutic agents. The shift from exclusive corticosteroid monotherapy to steroid-sparing immunomodulatory therapy reshaped the landscape of treating ocular inflammatory disease. Over time, with increased efforts, new therapies were studied, trialed, and brought to the market. Today, in comparison to any other time in history, physicians have available to them the largest array of effective agents for achieving the ultimate goal: corticosteroid-free, durable remission.

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Immunosuppressive Drugs

Cited by 3 publications

References 125 publications

Corticosteroid-Sparing Agents: Conventional Systemic Immunosuppressants

Corticosteroid-Sparing Agents: Conventional Systemic Immunosuppressants

Cyclophosphamide for Ocular Inflammatory Diseases

The Philosophy of Treatment of Uveitis: Past, Present and Future

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