Purpose
To compare the effects of adalimumab and placebo on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25) in subjects requiring high dose corticosteroids for active non-infectious intermediate-, posterior-, or pan-uveitis.
Methods
The VISUAL-1 clinical trial (NCT01148225) was a phase 3, randomized placebo-controlled study. It investigated the efficacy and safety of adalimumab (80 mg loading dose followed by 40 mg every other week) as maintenance therapy in subjects with active non-infectious intermediate-, posterior- or pan-uveitis. The VFQ-25 is a validated measure for assessing the impact of visual impairment from the patient’s perspective. The VFQ-25 total score is calculated as the mean of 11 vision-related domains and scores range from 0 (worst vision functioning) to 100 (best vision functioning). The VFQ-25 was administered at every scheduled study visit of the 80 Week trial. As a ranked secondary outcome, the change in VFQ-25 from best state achieved prior to Week 6 to the final / early termination visit was compared between adalimumab and placebo using ANOVA. To investigate the temporal effects of adalimumab and placebo on VFQ-25 in a robust manner, a longitudinal GEE model (which incorporated all VFQ-25 measurements) was estimated.
Results
The VISUAL-1 clinical trial enrolled a total of 217 subjects (110 adalimumab, 107 placebo). The mean VFQ-25 total scores for adalimumab and placebo are similar through the tapering period but subsequently diverge and maintain separation through week 80 (Figure 1). The average change in VFQ-25 total score from best state achieved prior to Week 6 to the final / early termination visit was -5.50 for placebo and -1.30 for adalimumab. This corresponds to a statistically significant and clinically meaningful1 increase of 4.20 (95% confidence interval [CI]: 1.02 - 7.38; P = 0.010) associated with adalimumab relative to placebo. The longitudinal model estimated a statistically significant treatment effect of adalimumab of 3.07 (95% CI: 2.09 - 4.06; P<0.001).
Conclusions
Treatment with adalimumab is associated with statistically significant improvements in visual functioning for subjects with active non-infectious non-anterior uveitis.