Real-World Data Support Extended Treatment With Adalimumab for Noninfectious Uveitis

February 19, 2018
The Center for Biosimilars Staff

While corticosteroids are a common treatment for uveitis, effective corticosteroid-sparing therapies are necessary to maintain disease control without risking corticosteroid-related adverse events.

Noninfectious uveitis, or inflammation of the uvea, is an immune-mediated ocular disease that is frequently associated with comorbid inflammatory diseases. Patients with noninfectious intermediate, posterior, or panuveitis are estimated to have a 10-fold higher risk of blindness or low vision compared with individuals without these conditions. While corticosteroids are a common treatment for uveitis, effective corticosteroid-sparing therapies are necessary to maintain disease control without risking corticosteroid-related adverse events (AE).

Adalimumab (Humira), which is approved to treat inflammatory diseases including uveitis, was successfully used in the VISUAL I and II studies to manage uveitis. The open-label extension study, VISUAL III, the 78-week results of which were published this month in Ophthalmology, seeks to evaluate the safety and efficacy of extended treatment with adalimumab in patients who successfully completed the 2 previous trials.

The multicenter, unmasked, uncontrolled, phase 3 extension study included 371 patients in the intent-to-treat set. All patients received open-label subcutaneous adalimumab at a dose of 40 mg every other week for the duration of the study, and were allowed to start, continue, escalate, or taper corticosteroids or immunosuppressive therapies during the trial. Patients could also have 2 periocular corticosteroid injections per eye per year.

The main outcome of the study was quiescence (no active inflammatory chorioretinal or inflammatory lesions, anterior chamber cell grade of 0.5+ or less, and vitreous haze grade of 0.5+ or less in both eyes), and efficacy was also assessed (no active inflammatory lesions, anterior chamber cell grade of 0.5+ or less, vitreous haze grade 0.5+ or less, central retinal thickness, best-corrected visual acuity, and the dose of uveitis-related corticosteroids and immunomodulators). Outcomes were evaluated in both eyes at every study visit (weeks 2, 4, 8, 12, and 18; then every 12 weeks until week 78).

At study entry, 65% of patients had active uveitis, and the remaining 35% had inactive uveitis. In total, 121 (33%) were receiving immunomodulators, and 151 (41%) were using corticosteroids at baseline. During the study, 30 (8%) started using immunomodulators, and 65 (18%) started using corticosteroids. Throughout the VISUAL III study, 33 patients (9%) received local corticosteroid injections.

At week 0, 93% of patients with active uveitis were not in quiescence. By week 12, 60% achieved quiescence (which remained stable at week 78). Of those achieving quiescence, 66% were corticosteroid-free at week 78, and 23% were receiving corticosteroids at doses of 7.5 mg per day or less.

Of those who entered the trial with inactive uveitis, 85% had quiescence at week 0. By week 78, 74% experienced quiescence; 96% of the inactive uveitis group that achieved quiescence were not taking corticosteroids at week 0, and 93% were not taking corticosteroids at week 78. Only 2 patients with inactive uveitis at the study entry were receiving more than 7.5 mg of corticosteroids per day to maintain quiescence at week 78.

The mean exposure to adalimumab for all patients was 117 weeks (±70 weeks), representing 953.7 patient years (PY). In total, there were 82 AEs leading to discontinuation, 157 serious AEs (of which 36 were considered to be at least possibly related to the study drug), and 30 non-serious allergic reactions. There was a low incidence of active tuberculosis (0.1 event/100 PY), opportunistic infections (0.5 events/100 PY), serious infections (4.0 events/100 PY) and malignancies (1.3 events/100 PY).

The researchers say that their study confirms and extends the findings of early open-label trials in which treatment with adalimumab enabled substantial tapering of immunosuppresive drugs while achieving disease control, and that adalimumab was well tolerated in this study, with no new safety signals identified.

“These data suggest that adalimumab can be used for intermediate, posterior, and panuveitis as an important therapeutic option allowing patients to achieve and maintain long-term disease control with or without adjunctive corticosteroids or immunomodulators,” say the authors.

Reference

Suhler EB, Adán A, Brézin AP, et al. Safety and efficacy of adalimumab in patients with noninfectious uveitis in an ongoing open-lable study: VISUAL III. [Published online February 8, 2018.] Ophtlamology. doi: 10.1016/j.ophtha.2017.12.039.

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