VISUAL III: Adalimumab proven safe, effective in patients with noninfectious uveitis
Treatment with adalimumab leads to quiescence, improved visual acuity and reduced daily uveitis-related systemic corticosteroid use in patients with active uveitis and sustained quiescence without a systemic corticosteroid dose increase among those with inactive uveitis at study entry, results of the VISUAL III trial have shown. Additionally, no new safety signals are found.
Intent-to-treat analysis was performed on 371 out of 424 patients, of which 242 (65 percent) had active uveitis at study entry. Of these, 145 (60 percent; nonresponder imputation [NRI]) achieved quiescence at week 78, and 95 of 143 (66 percent; as-observed) patients were corticosteroid free. Moreover, 129 of 371 (35 percent) patients had inactive uveitis. Ninety-six of 129 (74 percent) achieved quiescence at week 78, and 89 of these (93 percent) were corticosteroid free. [Ophthalmology 2018;125:1075-1087]
There was initial improvement in inflammatory lesions, anterior chamber grade and vitreous haze grade followed by decline in patients with active uveitis but remained stable in those with inactive uveitis. Best-corrected visual acuity (BCVA) improved in patients with active uveitis from weeks 0–78 (0.27–0.14 logMAR; left and right eyes; as-observed) and remained stable in those with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5–1.2 mg/day).
Compared with previous VISUAL trials, adverse events (AEs; 424 events per 100 patient-years) and serious AEs (16.5 events per 100 patient-years) were similar.
In previous studies, treatment with adalimumab significantly prolonged time to treatment failure (eg, flare) after corticosteroid cessation. [N Engl J Med 2016;375:932-943; Surv Ophthalmol 2016;61:1-17]
“However, in clinical practice, patients may receive systemic or topical corticosteroid support as needed for uveitis control,” researchers said. “[A]s such, corticosteroids were permitted as needed in the current trial.”
Furthermore, adalimumab therapy was well tolerated in this study, as shown by the low incidence of AEs of special interest and the absence of new safety signals beyond those previously reported with biologic therapy targeting tumour necrosis factor–α and in VISUAL I and II trials. [Retina 2006;26:1-16; N Engl J Med 2016;375:932-943; Arthritis Care Res (Hoboken) 2016;68:1078-1088; Arch Med Sci 2014;10:1175-1185]
Participants in this trial included those meeting treatment failure criteria or who completed VISUAL I or II (phase III, randomized, double-masked, placebo-controlled) without treatment failure. They received adalimumab 40 mg every other week. Interim follow-up data were described from weeks 0–78.
NRI was used to report binary data, last observation carried forward and as-observed analysis to describe continuous data, and observed-case analysis to assess corticosteroid dose.
“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,” researchers said. “Longer-term follow-up in VISUAL III is ongoing.”