Combination Therapy Superior in Managing Ocular Inflammation During Uveitis

A recent retrospective analysis comparing multiple frequently used antimetabolites to tumor necrosis factor inhibitors (TNFi) managing noninfectious ocular inflammation has indicated a favorite in corticosteroid sparing efficacy.

Standard treatment for uveitis generally focuses on systemic immunosuppression. Various studies have indicated the superiority of systemic medications over intravitreal corticosteroid implants; these medications consistently had similar or better visual outcomes with fewer systemic side effects. Additionally, TNFi therapies were confirmed not to lead to increased overall mortality.2,3

The most common methods of immunosuppressive agents used to treat uveitis are antimetabolites, particularly methotrexate and mycophenolate. Both medications are efficacious for ocular inflammatory diseases. However, little information exists comparing immunosuppressive agents. Investigators cited this as the motivation for the study.1

“Comparison of commonly used conventional antimetabolites and biologics for uveitis has not yet been reported,” wrote Sapna S. Gangaputra, MD, MPH, department of ophthalmology and visual sciences, Vanderbilt University Medical Center, and colleagues. “Here, we compare the corticosteroid sparing efficacy of frequently used antimetabolites for uveitis such as methotrexate (MTX), mycophenolate mofetil (MMF), azathioprine (AZA), and leflunomide (LEF) to frequently used TNF inhibitors for uveitis such as adalimumab (ADA) and infliximab (INF) in a large cohort study.”1

The team collected demographic data on patients from various uveitis clinics across the US, including every visit of each patient between clinic inception and December 2010. A patient’s eyes were classified as inactive if no inflammatory activity was noted, as well as if rare cells were noted without inflammation signs. An active grade was administered when the chart indicated evidence of active inflammation, such as anterior chamber cells or vitreous haze of ≥1+.1

A total of 1475 patients were eventually accepted into analysis. They were then split into three groups; the conventional antimetabolite (CONV) group, which consisted of 1218 patients; the TNFi only group, with 76 patients; and a combination group when CONV and TNFi were used concurrently (COMB), with 181 patients. Median age in the COMB group was 27.3 years (range 12.6-43.8), 40.5 in the CONV group (range 19.6-53.4), and 37.8 in the TNFi only group.1

Patients in the TNFi only group were more likely to exhibit anterior uveitis (41.4% in COMB and 36.8% in TNFi-only compared to 29.6% in CONV, P <.0033). Duration of uveitis, inflammatory activity levels, visual acuity and cohort entry, and use of topical corticosteroid more than 2 drops of prednisone acetate or equivalent, were similar between all groups.1

Eventually, given the similarities between the TNFi and COMB groups, investigators merged them for Cox multivariable analysis. Similar trends of higher success were indicated at every time point with the merged group, as compared to the CONV only group.1

Gangaputra and colleagues indicated that, contrary to previous studies, TNFi outcomes were substantially better than those achieved by CONV alone, especially when combined conventional immunosuppressants. A greater number of patients in the TNFi group exhibited recovery, and at a faster pace, than either of the other groups.1

“Our results suggest that for the average patient requiring immunosuppression for uveitis, treatment success occurs more often/faster with a combination of antimetabolite and a biologic, which likely has benefits in terms of avoidance of complications of uveitis and of systemic or topical corticosteroid therapy, as well as faster time to uveitis quiescence,” wrote Gangaputra and colleagues.1

References

1. Gangaputra SS, Newcomb CW, Ying G-S, et al. Effectiveness of frequently used TNF inhibitors vs. conventional immunosuppressive therapies for noninfectious uveitis. Ocular Immunology and Inflammation. Published online April 15, 2025:1-9. doi:10.1080/09273948.2025.2479802

2. Multicenter Uveitis Steroid Treatment Trial Research Group, Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Sugar EA. The multicenter uveitis steroid treatment trial: rationale, design, and baseline characteristics. Am J Ophthalmol. 2010;149(4):550-561.e10. doi:10.1016/j.ajo.2009.11.019

3. Kempen JH, Daniel E, Dunn JP, et al. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study. BMJ. 2009;339:b2480. Published 2009 Jul 3. doi:10.1136/bmj.b2480