Patients experienced prolonged time to treatment failure, meeting primary endpoints in VISUAL I and II trials.
Patients with uveitis experienced prolonged time to treatment failure when treated with adalimumab (HUMIRA, AbbVie) versus placebo, according to Pauline Merrill, MD, Assistant Professor of Ophthalmology at Rush University Medical Center.
The drug’s efficacy was significantly greater than placebo in patients with idiopathic uveitis overall in both the VISUAL I and VISUAL II trials, Merrill said.
“As you all know, the response to uveitis to various treatment modalities may vary significantly by etiology of uveitis. To date there has not been a prospective analysis to determine the efficacy of adalimumab among non-infectious uveitis of different etioligies,” she said in a presentation at the annual meeting of the American Society of Retina Specialists in Boston, MA.
In the VISUAL I (active uveitis) and VISUAL II (inactive uveitis) global phase 3 trials, Merrill and colleagues performed exploratory data analyses. Patients received placebo or adalimumab subcutaneously (80 mg week 0, followed by 40 mg every other week from week 1 up to 80 weeks).
Oral prednisone was tapered according to a pre-specified schedule. The primary endpoint of both studies was time to treatment failure, which was determined by multiple component endpoints.
“Subjects could meet the endpoint by meeting any one of these 4 criteria, including new coreoretinal or retinal lesions, worsening anterior chamber cell, vitreous haze or loss of visual acuity,” Merrill said.
One third of patients included in the trial had posterior uveitis, 40% had pan uveitis, and approximately 20% had intermediate uveitis.
“When breaking it down by specific diagnoses, we see that the idiopathic group also showed a statistically significant difference. The other subgroups all showed a trend in favor or adalimumab,” Merrill said. “We then wanted to look further at this idiopathic group and break it down into anatomic subgroups. In this analysis, all three subgroups — intermediate, posterior and pan uveitis of the idiopathic group – all showed a trend in favor of adalimumab, which did not meet statistical significance, presumably due to small population size.”
Similar results were shown in the VISUAL II trial, during which the idiopathic diagnosis reached statistical significance, and each subgroup showed a trend in favor of adalimumab, except for the sarcoidosis group.
“These exploratory analyses from the VISUAL I and II studies do show a significantly higher efficacy of adalimumab over placebo in patients with idiopathic uveitis, whether active or inactive,” Merrill said. “And when grouped by anatomic location, these subjects also showed a trend in favor of adalimumab in all three groups.”
According to Merrill, adverse events were similar between study groups, and no new safety signals were observed.
“There were no new unexpected adverse events, but of course with any TNF-inhibitor, it’s extremely important to rule out any infection, particularly TB [tuberculosis], before hand,” she said. “Look for any evidence of demyelinating disease, particularly in patients with intermediate uveitis. You always want to get an MRI before considering a TNF inhibitor such as adalimumab to make sure that you don’t put them at risk of progressing to MS [multiple sclerosis]. There was also a low rate of malignancy, but these are all well understood adverse events of HUMIRA from other studies.”
Merrill announced financial disclosures from AbbVie, Alimera, Allergan, Covalent and Santen.