David K. Scales
SAN ANTONIO – Biologic agents are an important new class of medications available for treating noninfectious uveitis, David K. Scales, MD, said here at the Anterior Segment Section Symposium during the American Academy of Optometry meeting.
Primary Care Optometry News sponsored the symposium.
Biologics were originally considered second- or third-line choices for treating noninfectious uveitis (NIU), said Scales, who practices at Retina and Uveitis Consultants of Texas in San Antonio, but now they are a first-line choice.
Humira (adalimumab, ABBvie) is now FDA-approved for this indication. “Look for new studies to expand treatment modalities,” he said.
He said research is ongoing involving EGP-437 (dexamethasone) for anterior segment ocular iontophoresis; ADX 102 (Aldeyra), a topical aldehyde inhibitor for treating anterior NIU; Janus kinase 1 inhibitor (filgotinib, Galapagos, NV), an oral agent for panuveitis or posterior segment NIU; and sirolimus (mTOR inhibitor) for intravitreal injection for treating panuveitis or posterior segment NIU.
There is a need for immunomodulating drugs in the management of NIU, Scales said. Classes of these types of agents include antimetabolites (azathioprine, methotrexate, mycophenolate), T-cell inhibitors (cyclosporine, tacrolimus), alkylating agents (cyclophosphamide, chlorambucil) and biologic agents (adalimumab, infliximab, rituximab, abatacept).
Corticosteroids are effective for NIU, have a rapid onset of action and are titratable; however, there is a high incidence of side effects, Scales said.
The Multicenter Uveitis Steroid Treatment trial had, “no shattering insights,” Scales said. “It concluded that local and implant steroids were effective for uveitis treatment, but there was a high incidence of local ocular side effects and systemic complications.”
Scales said when considering beginning immunomodulating agents, “You want to look at your dose and duration of corticosteroid agents (chronic use, unable to taper below 10 mg prednisone daily). You’re looking at three or four recurrences per year. Serpiginous chorioretinopathy is an exception; you have to put them on a systemic medication,” he said.
Also consider the severity of local and systemic complications, such as juvenile rheumatoid arthritis, Behcet’s disease, Wegner’s disease, Vogt-Koyanagi-Harada disease, sarcoid, birdshot chorioretinopathy and HLA-B27.
Current biologics used for NIU include tumor necrosis factor inhibitors such as infliximab by infusion, etanercept and subcutaneous adalimumab, and anti-CD20 monoclonal antibodies, including rituximab by infusion.
Jaffe and colleagues compared adalimumab to placebo for the treatment of NIU in a study funded by AbbVie.
Adalimumab halved the failure rate and extended the time to failure rate by almost double, Scales said.
According to the study, the primary efficacy end point was the time to treatment failure at or after week 6, and results showed treatment failure at 24 weeks in the adalimumab group and 13 weeks in the placebo group.
Secondary end points included change in anterior chamber cell grade, vitreous haze grade and best corrected visual acuity, and they were significantly better in the adalimumab group.
The authors concluded: “In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo.”
In practice, “You want to suppress the inflammation with an oral steroid while starting the biological agent,” Scales said. “In most cases, use 1 mg/kg for the initial dose (60 mg prednisone/day) and taper off over 4 to 6 weeks if quiet. Most immunotherapeutic agents, including biologics, will need 4 to 6 weeks for onset of action.”
Scales reviewed important considerations prior to initiating therapy.
Patients who test positive for tuberculosis or hepatitis should be excluded, rule out multiple sclerosis or a history of optic neuritis (if in doubt, obtain an MRI or brain or neuro consult), rule out the risk of heart failure developing or worsening, and coordinate care with internal medicine (such as rheumatology and hematology), he said.
Scales said complications of biologics when used for NIU may include: rash/allergic reaction, immune reaction such as lupus, development of severe infections, liver dysfunction, blood dyscrasias, heart failure developing or worsening, activation or reactivation of tuberculosis, multiple sclerosis activation or reactivation, immunosuppression and increased risk of infection, and risk of developing a malignancy. – by Nancy Hemphill, ELS, FAAO
Jaffe GJ, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa150985.
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, et al. Ophthalmology. 2011;doi:10.1016/j.ophtha.2011.07.027.
Whitley W, et al. Biologic therapy: Applications in anterior segment disease. Presented at: American Academy of Optometry meeting; San Antonio; November 6-10, 2018.
Disclosure: Scales reported no relevant financial disclosures.