Adalimumab Improves Uveitis, Studies Show

Treatment with adalimumab is shown to improve function and quality of life for patients with active non-infectious intermediate, posterior and panuveitis, according to a study presented at the 2015 ACR/ARHP annual meeting in San Francisco, Calif.

The study, presented on Nov. 9, shows that when compared with placebo (n=107), the primary endpoint of time-to-treatment failure in the phase 3 VISUAL-1 study of adalimumab (n=110) (80 mg loading, 50 mg Q2W maintenance), revealed a significant benefit with adalimumab, said the study’s author, John Sheppard, M.D., of Eastern Virginia Medical School, Norfolk, Va.

“We are pleased that the visual signs we see through the slit lamp and with our indirect ophthalmoscope correspond to the ability to function in these patients. The improvements in the eye corresponds to tremendous improvement in quality of life,” Dr. Sheppard said.

The secondary endpoint in VISUAL-1 of VFQ-25 total score is a measure of 12 health domains most important for patients with chronic eye diseases (11 vision-related, 1 general health; range 0-100 for each with 100 being best). It includes items related to general vision, ocular pain, distance activities, social functioning and driving. Investigators devised a longitudinal model to assess adalimumab and placebo effects on VFQ-25 scores, plotting mean VFQ-25 total score values with each study visit, and noting changes from best state achieved prior to the sixth week.

While all patients experienced an increase of 6.14 during the steroid burst, the subsequent average monthly score decline was greater in the placebo group at 0.25 as compared with 0.07 for the adalimumab group. The mean difference at week 80 between adalimumab and placebo was a significant 2.98 (95% CI 0.005-5.96, p=0.0496).

Both groups in the study received a six-week steroid burst and taper.

“Understanding and evaluating vision-targeted health-related quality of life metrics among uveitis patients is important,” Dr. Sheppard said.

Adalimumab Lowers Risk for Uveitis Recurrence

In a separate study presented at 2015 ACR/ARHP, researchers showed that adalimumab lowered the risk for uveitis recurrence, vision loss and macular edema in patients with active, noninfectious intermediate, posterior or panuveitis.

The study included 217 patients who were prescribed adalimumab (80 mg loading dose, then 40 mg Q2W). The patients were randomized 1:1 to receive placebo or adalimumab (80 mg loading dose, 40 mg at week 1, followed by 40 mg every other week) for ≤80 weeks.

Researchers, led by James T. Rosenbaum, M.D., of Oregon Health and Science University in Portland, found that patients receiving adalimumab were less likely to experience treatment failure (HR=0.50; 95% CI, 0.36-0.70; P<0.001), with fewer associated treatment failure causes. Median time to treatment failure was 13 weeks for placebo and 24 weeks for adalimumab.

In a post-hoc analysis of macular edema, the risk for macular edema was reduced by 67% in the adalimumab group versus placebo (HR=0.33; 95% CI, 0.12-0.90; P=0.023).

Despite the use of corticosteroids, adalimumab significantly lowered the risk for recurrence of uveitic activity and vision loss.

While treatment of uveitis has traditionally relied on corticosteroids, ocular or systemic adverse effects can accrue with long-term use. The FDA has approved non-corticosteroid immunomodulatory agents for uveitis. Other drugs that have been tried as treatments for uveitis have failed or have been inconsistent (eg., calcineurin and mTOR inhibitors, anti-IL-17A, anti-IL-1 beta).

Although anterior uveitis is usually treated successfully with topical corticosteroids, intermediate, choroid, retinal and panuveitis often continue to threaten vision, Dr. Rosenbaum said.

Adalimumab’s safety profile was consistent with its known profile across approved indications. Adverse events were similar between the adalimumab and placebo groups.

References:

"Effect of Adalimumab on Visual Functioning (VFQ-25) in Visual-1 Trial Patients with Non-Anterior Non-Infectious Uveitis,"  John Sheppard.  Nov. 9, 2015. ACR/ARHP 2015. Abstract number 2039.

"Adalimumab in Patients with Active, Noninfectious Uveitis Using High-Dose Corticosteroids,"

 James T. Rosenbaum, Nov. 9, 2015. ACR/ARHP 2015. Abstract number 2038.