Ophthalmology Xagena

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Xagena Newsletter

Biologics in the treatment of uveitis in patients who are refractory to more traditional immunosuppressive therapies

Corticosteroids are the mainstay of treatment for immune-mediated diseases, including non-infectious uveitis and ocular inflammation, because they are inexpensive, potent and rapidly effective. However, corticosteroid-sparing immunosuppressive agents are required in a minority of patients to either control vision- or life-threatening autoimmune disease or to minimize toxicities associated with prolonged use of corticosteroids. Biologic therapy can be an alternative in patients with inadequate response to or tolerance of conventional immunotherapy.

The biologics were initially developed to treat systemic inflammatory diseases or to prevent organ transplant rejection, but have been used off-label to treat uveitis or ocular inflammation.
Ocular inflammation can occur with many of these diseases, including inflammatory bowel disease ( IBD ), ankylosing spondylitis ( AS ), psoriasis, Behcet’s disease ( BD ), juvenile idiopathic arthritis ( JIA ) and rheumatoid arthritis ( RA ).

Biologics are relatively new medications, and data on both efficacy and safety of these agents used to treat ocular conditions are limited. To date, none of the biologics have been approved for the treatment of ocular inflammation. Off-label use of biologics to treat ocular immune-mediated diseases has appeared in a number of reports, all of them primarily uncontrolled small case series. The preponderance of literature describing biologic treatment of uveitis is with the tumor necrosis factor inhibitors ( Infliximab, Etanercept and Adalimumab ), followed by the IL-2 receptor ( IL2-R ) blocker Daclizumab.

Biologics are useful when standard immunosuppression has failed or has been poorly tolerated, or to treat patients with concomitant ocular and systemic inflammation that might benefit from these medications. Given their cost as well as the limited long-term safety data, researchers do not routinely recommend biologics as first-line therapy.
Situational exceptions for earlier use may be made for BD-associated uveitis, where Infliximab has been demonstrated to be rapidly effective.
Consideration may also be given to earlier use of biologics in patients with systemic disease, such as rheumatoid arthritis, AS and JIA, particularly when institution of such therapy will provide treatment benefit for both systemic and ocular inflammation.
Excepting these situations, researchers generally reserve biologics for cases where standard immunosuppression has either failed or been poorly tolerated due to side effects, or in diseases known to be associated with a high risk of vision loss or irreversible complications related to uncontrolled inflammation.

In general, antibodies created fully or in part from nonhuman DNA ( e.g., Infliximab ) are more likely to cause hypersensitivity reactions and to result in the creation of neutralizing antibodies when compared to fully humanized ( e.g., Adalimumab ) antibodies. This is why Infliximab is always given with a second immunosuppresive agent, typically Methotrexate, to suppress the formation of such unwanted antibodies, whereas use of a second agent in association with Adalimumab is optional.
Infliximab-associated infusion reactions can be severe, but are usually mild and treatable with antihistamines and/or corticosteroids.
Etanercept and Adalimumab are administered by subcutaneous injection and may cause self-limited inflammation at the injection site.
Other biologics can also cause hypersensitivity reactions, headache, flu-like symptoms, gastrointestinal adverse effects, and they also may increase risk of infection and malignancy.

Biologics that are FDA-approved in systemic pediatric diseases include Infliximab ( Crohn’s disease; more than 6 years old ), Etanercept ( JIA; more than 2 years old ), Adalimumab ( JIA; more than 4 years old ), Daclizumab ( organ transplant; more than 11 months old ) and Abatacept ( JIA; more than 6 years old ).
Rituximab and Anakinra have been used off-label in children, but are not FDA-approved in children. ( Xagena )

Pasadhika S et al, Review of Ophthalmology 2010