First-Line Therapy for Non-Infectious Uveitis

Uveitis experts agree that biologics are effective in treating non-infectious uveitis (NIU), but opinions differ regarding their use as a first-line therapy.

In a point-counterpoint discussion, Sapna Gangaputra MD took the pro position. She emphasised that biologic treatment has a faster onset of efficacy, translating into earlier vision improvement and quicker attainment of corticosteroid sparing or discontinuation compared with traditional immunomodulatory therapy (IMT). She also reviewed evidence addressing safety concerns and noted patients on biologics require less frequent laboratory monitoring than those on IMT.

“Traditional IMT is great, but biologics are better,” Dr Gangaputra said.

Arthi Venkat MD conceded that patients started on biologics are slightly more likely to achieve corticosteroid sparing but said the difference compared with IMT is small and offset by the downsides of biologics, which include their higher cost burden and risk of adverse events.

“Traditional IMT for treatment of NIU has been around a long time and is perfectly reasonable to be first-line therapy for NIU because it is tried and true, affordable, and safe,” she said.

The case for biologics

Dr Gangaputra noted that in 2014, an expert panel recommended considering the TNF inhibitors infliximab and adalimumab as first-line immunomodulatory agents for treating ocular manifestations of Behçet’s disease and as second-line therapy for uveitis associated with juvenile idiopathic arthritis (JIA) or for the treatment of severe cases where traditional IMT failed or was unsuitable.¹ The recommendations considered safety concerns associated with the biologics, including risks for tuberculosis (TB) reactivation, opportunistic infections, demyelinating disease, paradoxical autoimmune adverse events, anti-idiotypic antibody development, and lymphoma.

“A huge volume of data has emerged since then, mostly from the SITE cohort study that found that the risk of overall mortality and of cancer-related mortality in patients being treated for eye disease was not much different in those receiving biologics compared with traditional IMT,²” Dr Gangaputra said.

Reviewing the literature, she also concluded that there is solid evidence supporting the effectiveness of biologics, citing results from the retrospective SITE study showing treatment with a TNF inhibitor—alone or combined with a traditional IMT agent—was more effective than conventional IMT for achieving disease quiescence and corticosteroid sparing among patients with active NIU.² Similarly, the proportion of patients achieving corticosteroid sparing at 6 months and corticosteroid discontinuation at 12 months was higher in the group treated with adalimumab versus the IMT group in the prospective, randomised ADVISE trial.³

Dr Gangaputra also mentioned the ADJUST study, which found that among patients whose disease was controlled on adalimumab, adding a traditional disease modifying antirheumatic drug did not protect against treatment failure (disease recurrence) after adalimumab was discontinued. Importantly, all patients who restarted adalimumab because of treatment failure regained disease control.

“We repeatedly say that we don’t treat uveitis but that we immunosuppress patients to control the disease,” she said. “The biologic was the only thing allowing these children to regain good control.”

Justification for traditional IMT

“We are not arguing that traditional IMT is better than biologic therapy in all scenarios and for all NIU. And I am not arguing against the use of biologics altogether or that biologics do not work,” Dr Venkat said. “Rather, the issue we are debating is that traditional IMT with an antimetabolite or calcineurin inhibitor is an appropriate and better first-line agent than biologic therapy for NIU.”

Reviewing IMT efficacy, Dr Venkat also mentioned the SITE study, noting it showed most NIU patients (80% to 85%) were managed on a single nonbiologic immunosuppressive. She added data from head-to-head comparative trials showed that the difference between adalimumab and IMT in percentage of patients achieving corticosteroid sparing is only 5% to 10%. Putting the difference in perspective, Dr Venkat offered an analogy comparing a luxury brand and a high-quality duplicate.

“The duplicate does the same thing but for a lot less money,” she said.

Dr Venkat cited several studies documenting the overall tolerability and safety of traditional IMT and stated that, compared with IMT, biologics are associated with higher rates of infections and TB reactivation.

“Those of us who routinely practice uveitis care know there is a lot of latent TB out there,” she commented.

Further arguing against first-line use of biologics, Dr Venkat emphasised the risks of demyelinating disease and formation of anti-idiotypic antibodies that render biologics ineffective. Discussing cost, she reviewed research showing that, in general, the incremental cost-effectiveness ratio is high for biologic therapy and cautioned that biologic treatment for NIU is often not completely covered by insurance.

The debate took place during AAO 2025 in Orlando, US.

Sapna Gangaputra MD, MPH is Associate Professor, Vanderbilt Eye Institute, Nashville, Tennessee, US. sapna.gangaputra@vumc.org

Arthi Venkat MD, MS is Associate Professor of Ophthalmology, University of Virginia School of Medicine, Charlottesville, Virginia, US.

1. Levy-Clarke G, et al. Ophthalmology, 2014; 121(3): 785–796.e3.

2. Kempen JH, et al; Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Research Group. Ophthalmology, 2023; 130(12): 1258–1268.

3. Jabs DA, et al. Ophthalmology, 2025 Oct 10: S0161-6420(25)00639-6. Epub ahead of print.

4. Acharya NR, et al. Lancet, 2025; 405(10475): 303–313.