Real-World Evidence Supports Efficacy of Adalimumab for Pediatric Non-Anterior Uveitis

New research suggests the highly effective therapeutic role of adalimumab treatment in avoiding or reducing ocular inflammation in pediatric patients with noninfectious non-anterior uveitis.¹

Investigators, led by Luca Cantarini, MD, Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, indicated most patients did not experience ocular flare after the start of adalimumab during a median follow-up of 17.5 months, while others experienced a decrease in the frequency and/or severity of ocular inflammatory episodes.

“As a whole, none of the patients enrolled experienced a lack of response to adalimumab,” investigators wrote. “This is even more remarkable when considering the severity of patients included in the study.”

Over the past decade, tumor necrosis factor (TNF) inhibitors have emerged as useful therapies for pediatric patients with resistant or severe uveitis. Adalimumab, a fully humanized monoclonal antibody, is the only biotechnological agent currently approved by the US Food and Drug Administration (FDA) and European Medicines Agency for the treatment of adult non-infectious non-anterior uveitis.² Although clinical trials remain ongoing, treatment for uveitis is generally based on expert opinion and algorithms proposed by multidisciplinary trials.

Investigators pointed to international registries dedicated to patients with uveitis as avenues to acquire new strong evidence from real-life experience and facilitate enrollment in clinical trials. Using data from the AutoInflammatory Disease Alliance (ADA), the current analysis investigated the therapeutic role of adalimumab in pediatric patients with intermediate uveitis/pars planitis, posterior uveitis, and panuveitis.

Trained ophthalmologists were required to provide details about the anatomical and pathogenic classification of uveitis, the type of presentation, and ocular disease course, according to the standardized uveitis nomenclature (SUN) working group. An ocular flare was defined as a worsening of inflammatory activity after a period of inactive disease, as classified in the SUN group nomenclature.

The primary endpoint for the study was a representation of the frequency of patients with complete and persistent control of ocular inflammation, those with a decrease in severity and/or frequency of ocular flares, and those with no improvement after the introduction of adalimumab. Medical records of 21 pediatric patients from 6 centers involved in the AIDA Network were reviewed from the retrospective phase of the AIDA project.

For this population, the mean duration of the adalimumab treatment was 30.47 months and represented the first biologic agent utilized in all enrolled patients. All cases indicated clinical efficacy as soon as the 3-month follow-up assessment. The analysis showed 11 patients (19 affected eyes) did not experience further ocular inflammation after adalimumab introduction and were considered fully responsive patients.

Moreover, 10 cases (17 affected eyes) showed a significant clinical improvement, including reduced frequency and severity of ocular relapses in 4 patients; reduced frequency of ocular relapses in 3 patients; and reduced severity of ocular relapses in 3 patients. They were included in the group of “less responsive” patients, while no patients were unresponsive to treatment. Overall, the study recorded 94 relapses in the year prior to the start of adalimumab, corresponding to 3.91 ocular flares per patient year.

On the other hand, the total number of relapses occurring during adalimumab treatment was 33, corresponding to 1.1 flares per patient-year (P = .0009). At the start of treatment, macular edema and retinal vasculitis were observed in 18 eyes and 20 eyes, respectively; at the last assessment, macular edema was observed in 4 eyes, and retinal vasculitis in 2 eyes. Despite poor BCVA at the start of treatment, BCVA improved in 8 eyes and only 2 eyes experienced sight worsening.

The investigative team observed a non-statistically significant decrease in the number of patients requiring glucocorticoids at the last assessment compared to that observed at the start of adalimumab (P = .12). Meanwhile, the mean daily glucocorticoid dosage significantly decreased, from 26.8 ± 16.8 mg/day at adalimumab introduction to 6.25 ± 6.35 mg/day at the last assessment (P = .002). In terms of safety, a single adverse event in one patient was reported during the study period, consisting of a generalized adenopathy developed during adalimumab treatment.

Notably, the analysis suggests intermediate uveitis/pars planitis and posterior uveitis were more frequent among patients with a full response to adalimumab, while panuveitis was more frequent among those continuing the experience flares, despite improvements in the frequency and severity of said episodes.

Investigators noted it could be related to a more aggressive treatment at the introduction of adalimumab, as both conventional disease modifying anti-rheumatic drugs (cDMARDs) and systemic corticosteroids were more frequently used in eyes with intermediate uveitis/pars planitis. However, these findings lost statistical significance during follow-up.

“These findings seem to suggest that a more aggressive treatment of panuveitis and posterior uveitis at the start of adalimumab could increase the likelihood of fully respond to therapy,” investigators wrote.

References

1. Vitale, A., Casa, F.D., Guerriero, S. et al. Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry. Ophthalmol Ther (2023). https://doi.org/10.1007/s40123-023-00712-1
2. Suhler EB, Ada´n A, Bre´zin AP, et al. Safety and efficacy of adalimumab in patients with noninfectious uveitis in an ongoing open-label study: VISUAL III. Ophthalmology. 2018;125(7):1075–87. https://doi.org/10.1016/j.ophtha.2017.12.039.