Adalimumab Provides Superior Corticosteroid Sparing Versus Standard Immunosuppressants in Uveitis

Adalimumab treatment outperformed antimetabolites and calcineurin inhibitors in patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis requiring immunosuppression, based on results from the Adalimumab versus Conventional Immunosuppression for Uveitis (ADVISE) trial.¹

Adalimumab, first approved for uveitis in 2016, has long been proven to prolong the time to uveitis relapse compared to placebo after discontinuation of prednisone. Additionally, further investigation suggested that a substantial proportion of patients involved in these trials achieved successful corticosteroid sparing.²

“However, the relative merits of adalimumab versus conventional immunosuppressive drugs for the treatment of uveitis is not known,” wrote Douglas Jabs, MD, director of the Center for Clinical Trials and Evidence Synthesis at the Johns Hopkins University Bloomberg School of Public Health, and colleagues. “Therefore, we performed a randomized comparative effectiveness trial, the ADVISE trial, to compare adalimumab with conventional immunosuppressive drugs (CIDs) for the treatment of noninfectious intermediate uveitides, posterior uveitides, and panuveitides.”¹

ADVISE was a multicenter, randomized, unmasked, parallel-treatment, comparative effectiveness, superiority trial conducted at 26 clinical centers in the US, UK, and Australia. Eligible patients were adults or adolescents ≥13 years old with active or recently active noninfectious intermediate, posterior, or panuveitis for whom immunosuppression was indicated. Additionally, patients were required to either be receiving prednisone >7.5 mg/day or have an anticipated dose increase to >7.5 mg/day.¹

Patients were excluded if they had active or untreated latent tuberculosis, multiple sclerosis, or magnetic resonance imaging (MIR) findings consistent with demyelination, Behçet disease, a long-acting intravitreal corticosteroid implant placed within 3 years, or current therapy with 2 immunosuppressive drugs, among other criteria.¹

Patients were then randomly assigned in a 1:1 ratio to either adalimumab or CID treatment. Those receiving adalimumab were given a loading dose of 80 mg subcutaneously, followed by 40 mg 1 week later and then every 2 weeks. Those in the CID arm already receiving 1 immunosuppressive drug at baseline were given a second drug of a different class, while those with no immunosuppression received an antimetabolite, either methotrexate 15 mg/week or mycophenolate mofetil 1 g twice daily.¹

Jabs and colleagues followed up with patients every month for 6 months, then every 2 months for another 6 months before closing out at 1 year. Each visit saw participants provide medical, ophthalmic, and treatment history, undergoing an assessment of best-corrected visual acuity (BCVA) via a complete eye examination, logarithmic eye charts, and other methods.¹

A total of 227 patients were initially enrolled, of whom 10 were lost to follow-up at 6 months and 10 more at 12 months. This number was higher among the CID group than the adalimumab group at both intervals. By 6 months, 69% of patients in the adalimumab arm saw successful corticosteroid sparing, compared to 54% in the CID arm (OR, 1.86; 95% CI, 1.06-3.25; P = .029); by 12 months, these percentages had risen to 86% and 77%, respectively (OR, 1.89; 95% CI, 0.93-3.83; P = .077).1 Successful corticosteroid discontinuation occurred in 55% of patients in the adalimumab arm versus 40% receiving CID (OR, 1.85; 95% CI, 1.06-3.19; P = .028).¹

Despite these data, Jabs and colleagues noted several potential limitations to the ADVISE trial. Among these, the trial’s unmasked state could have influenced individual patients’ quality-of-life assessments. Additionally, the team highlighted that the CID group appeared to be catching up to the adalimumab group in the proportion of successful corticosteroid sparing. They indicated that this may reflect a difference in rapidity and not efficacy.¹

However, the investigators ultimately concluded that adalimumab outperformed standard CID therapy across all timepoints, ostensibly displaying its superior efficacy.

“In the ADVISE Trial, adalimumab’s effect was faster for successful corticosteroid sparing by 6 months and a greater proportion of participants achieved successful corticosteroid discontinuation by 12 months,” Jabs and colleagues wrote.¹

References

1. Jabs DA, Sugar EA, Burke AE, et al. Adalimumab versus conventional immunosuppression for uveitis (advise) trial. Ophthalmology. 2025;133(3):310-325. doi:10.1016/j.ophtha.2025.10.004

2. Suhler EB, Jaffe GJ, Fortin E, et al. Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis. Ophthalmology. 2021;128(6):899-909. doi:10.1016/j.ophtha.2020.10.036