Immunosuppressive drugs can manage ocular inflammatory disorders

Concerns regarding corticosteroid side effects may lead to increased use of immunosuppressive drugs.

BALTIMORE — Treating ocular inflammatory disorders with judicious use of immunosuppressive drugs will benefit many patients by providing better long-term control of ocular inflammation or a decrease in corticosteroid side effects, according to recommendations of an expert panel published in the American Journal of Ophthalmology.

The 12-person panel comprised physicians with expertise in ophthalmologic, pediatric and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care. The panel acknowledged that oral corticosteroids represent one of the mainstays in the management of patients with ocular inflammation. However, immunosuppressive drugs may also be used in the management of these patients because of concerns over the severity of the disease, the presence of corticosteroid side effects, and the requirement for doses of systemic corticosteroids that will likely result in corticosteroid complications.

“Oral corticosteroids are very effective. They remain the first-line therapy for many diseases,” said first author Douglas A. Jabs, MD, MBA, a professor of ophthalmology and of medicine here at The Johns Hopkins University of Medicine. Nonetheless, “their long-term use is often associated with a variety of dose-related adverse side effects.” In addition, “there are selected diseases where steroids alone appear to be inadequate for long-term management.”

Warranted conditions

Milder forms of ocular inflammation, such as those originating in the anterior segment, can often be successfully treated with topical or periocular corticosteroids. “Those diseases that require oral corticosteroids or immunosuppressive drugs are typically posterior-segment inflammation, panuveitis and severe external disease,” Dr. Jabs told Ocular Surgery News. In most cases, prescribing immunosuppressive drugs “is a collaborative activity between an experienced uveitis specialist and an internist.”

Immunosuppressive drugs may require long-term or even indefinite therapy. “The practitioner also needs to have an extended discussion with the patient about the potential risks and benefits,” Dr. Jabs said. Regular monitoring for toxicity is required, as well as a level of skill in their use. “Barring those caveats, these drugs can be very effective,” he said.

Immunosuppressive drugs “need to be tailored to the individual patient based upon the disease process and the patient’s general health status,” Dr. Jabs said. For instance, a patient with underlying renal disease “may not be a good candidate for cyclosporine because of its renal toxicity.” Likewise, a patient who has liver disease should not receive methotrexate because of its hepatic toxicity. On the other hand, methotrexate “has a very good track record in children with juvenile rheumatoid arthritis,” Dr. Jabs said. In short, “there is a fair amount of judgment that goes into the use of these drugs.”

Combination therapy

Combination therapy is appropriate in nearly all cases. “Patients will be treated with both corticosteroids and an immunosuppressive drug initially,” Dr. Jabs said. “You need an immediate anti-inflammatory effect from the corticosteroids, while an immunosuppressive drug typically takes a couple weeks to have an effect on the disease. The goal with the corticosteroids is to either discontinue or taper to a very low level over the ensuring 2 to 3 months.”

Combining two immunosuppressive drugs may also be considered when a corticosteroid/immunosuppressive regimen fails: for example, “choosing an antimetabolite and a T-cell inhibitor together, along with perhaps a corticosteroid,” Dr. Jabs said.

Selected diseases, because of their poor natural history, are ideal for immunosuppressive drug therapy from nearly the time of diagnosis. Bechet’s disease with posterior segment involvement and mucous membrane pemphigoid with ocular involvement are strong candidates. However, “in the case of scleritis with an underlying vasculitis, you will need to treat the underlying vasculitis,” Dr. Jabs said.

For some diseases, such as serpiginous choroidopathy, benefits of immunosuppression are less clear. “There is still a responsible rationale for considering their use, though,” he said.

Severity factor

For uveitis, “the need for immunosuppressive therapy will vary depending on the severity of the underlying disease,” Dr. Jabs said. About 15% of patients with pars planitis will require immunosuppressive drugs, compared to 69% for sympathetic ophthalmia and 25% for scleritis overall.

The authors caution extreme care when prescribing any corticosteroid or immunosuppressive drug during pregnancy. “The available data suggests that of all available treatments, oral corticosteroids are probably the safest,” Dr. Jabs said. In children, immunosuppressive drugs may interfere with nutrition, thus impacting growth indirectly.

Biologic agents for immune modulation are the focus of research. “These agents attack specific targets in the immune system,” Dr. Jabs said. Drugs such as etanercept, infliximab and daclizumab have been shown to be effective for non-ocular autoimmune disorders. “We’ll probably know within a few years how useful these drugs are for treating eye disease,” Dr. Jabs said.

For Your Information:

• Douglas A. Jabs, MD, MBA, can be reached at 550 N. Broadway, Ste. 700, Baltimore, MD 21205; (410) 955-1966; fax: (410) 955-0629; e-mail: djabs@jhmi.edu. Dr. Jabs has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Reference:

• Jabs DA, Rosenbaum JT, Foster S, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130:492-513.