The efficacy of Adalimumab in treatment of pediatric noninfectious uveitis and the factors influencing the efficacy_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhang Chunbo ¹ , Chen Ying ² , Min Hui ¹ , Xue Xiaorong ¹ , Zhai Yuyao ¹ ,  Zeng Rong ²

1. Department of Pharmacy, Xi'an People’s Hospital (Xi'an Fourth Hospital), Xi'an 710004, China;
2. Shaanxi Eye Hospital, Xi'an People’s Hospital (Xi'an Fourth Hospital), Xi'an 710004, China;

Corresponding author：

Zeng Rong, Email: 410531950@qq.com

Keywords：

Adalimumab; Pediatric noninfectious uveitis; Influence factor analysis

DOI：

10.3760/cma.j.cn511434-20241210-00475

Video：

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Objective To investigate the clinical efficacy and factors influencing treatment of pediatric noninfectious uveitis with Adalimumab (ADA). Methods A retrospective clinical study. A total of 86 pediatric patients with non-infectious uveitis, diagnosed and treated with ADA at Department of Uveitis Specialist of Xi'an People's Hospital (Xi' an Fourth Hospital) from January 1, 2021 to December 31, 2023, were included in this study. The age of all patients was ≤16 years. Among them, 55 (63.95%, 55/86) patients received ADA combined with one immunosuppressive agent, 28 (32.56%, 28/86) patients received ADA combined with ≥2 immunosuppressive agents, and 3 (3.49%, 3/86) patients received ADA alone without any immunosuppressive agents. All patients underwent best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The thickness of the retinal nerve fiber layer (RNFL) in the macular region was measured using an OCT device. The cumulative treatment effectiveness rate at 12 months post-treatment was evaluated using the Kaplan-Meier survival analysis. Multivariate analysis was performed using the Cox proportional hazards regression model, and the optimal predictive model was selected based on the Bayesian information criterion. The association between different treatment regimens and various clinical outcomes was assessed.Results Among the 86 pediatric patients, 42 were male and 44 were female, with a mean age of (10.47±3.23) years. The distribution of uveitis types was as follows: anterior uveitis in 37 cases, intermediate uveitis in 15 cases, posterior uveitis in 10 cases, and panuveitis in 24 cases. Anterior chamber cells (ACC), keratic precipitates, and synechiae were present in 66, 55, and 38 cases, respectively. The cumulative treatment effectiveness at 12 months was 85.1% [95% confidence interval (CI) 71.9-92.2], with a median time to treatment effectiveness of 3 months. Compared with baseline, after 6 months of treatment, the BCVA, RNFL thickness (Z=−6.323, −8.017), and the grading of ACC and vitreous haze (χ²= −6.917, −5.027) showed significant improvement, with statistically significant differences (P＜0.05). Multivariate analysis revealed that ACC (hazard ratio=22.31, 95%CI 2.43-204.68) and anterior uveitis (hazard ratio=3.88, 95%CI 2.03-7.42) were significantly associated with treatment effectiveness (P＜0.05). Patients with ACC had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 95.5% (95%CI 86.3-98.5). Patients with anterior uveitis had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 97.3% (95%CI 81.3-99.6). Patients without anterior uveitis had a median time to treatment effectiveness of 5 months, with a 12-month cumulative treatment effectiveness of 76.7% (95%CI 54.1-88.2). The cumulative recurrence risk at 12 months was 15.6% (95%CI 6.2-24.1). Conclusion ADA is safe and effective in treating pediatric non-infectious uveitis, and ACC and anterior uveitis are associated with response rate.

Citation： Zhang Chunbo, Chen Ying, Min Hui, Xue Xiaorong, Zhai Yuyao, Zeng Rong. The efficacy of Adalimumab in treatment of pediatric noninfectious uveitis and the factors influencing the efficacy. Chinese Journal of Ocular Fundus Diseases, 2025, 41(7): 520-526. doi: 10.3760/cma.j.cn511434-20241210-00475 Copy

1.	Maleki A, Anesi SD, Look-Why S, et al. Pediatric uveitis: a comprehensive review[J]. Surv Ophthalmol, 2022, 67(2): 510-529. DOI: 10.1016/j.survophthal.2021.06.006.
2.	Sharon Y, Friling R, Luski M, et al. Uveitic glaucoma: long-term clinical outcome and risk factors for progression[J]. Ocul Immunol Inflamm, 2017, 25(6): 740-747. DOI: 10.1080/09273948.2016.1255341.
3.	Ramanan AV, Dick AD, Jones AP, et al. Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis[J]. N Engl J Med, 2017, 376(17): 1637-1646. DOI: 10.1056/NEJMoa1614160.
4.	Quartier P, Baptiste A, Despert V, et al. ADJUVITE: a double-blind, randomised, placebo- controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis[J]. Ann Rheum Dis, 2018, 77(7): 1003-1011. DOI: 10.1136/annrheumdis-2017-212089.
5.	海峡两岸医药卫生交流协会风湿免疫分会眼免疫学组. 抗肿瘤坏死因子-α单克隆抗体治疗非感染性葡萄膜炎中国专家共识[J]. 中华眼底病杂志, 2024, 40(1): 8-19. DOI: 10.3760/cma.j.cn511434-20231201-00473.Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association. Chinese expert consensus on treatment of non-infectious uveitis with anti-tumor necrosis factor-alpha monoclonal antibody[J]. Chin J Ocul Fundus Dis, 2024, 40(1): 8-19. DOI: 10.3760/cma.j.cn511434-20231201-00473.
6.	Mccracken C, Yeh S, Jenkins K, et al. Timing of infliximab and adalimumab initiation despite methotrexate in children with chronic non-infectious anterior uveitis[J]. Eye (Lond), 2019, 33(4): 629-639. DOI: 10.1038/s41433-018-0283-0.
7.	Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop[J]. Am J Ophthalmol, 2005, 140(3): 509-516. DOI: 10.1016/j.ajo.2005.03.057.
8.	Nussenblatt RB, Palestine AG, Chan CC, et al. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis[J]. Ophthalmology, 1985, 92(4): 467-471. DOI: 10.1016/s0161-6420(85)34001-0.
9.	Touhami S, Diwo E, Seve P, et al. Expert opinion on the use of biological therapy in non-infectious uveitis[J]. Expert Opin Biol Ther, 2019, 19(5): 477-490. DOI: 10.1080/14712598.2019.1595578.
10.	Jaffe GJ, Dick AD, Brezin AP, et al. Adalimumab in patients with active noninfectious uveitis[J]. N Engl J Med, 2016, 375(10): 932-943. DOI: 10.1056/NEJMoa1509852.
11.	Lerman MA, Burnham JM, Chang PY, et al. Response of pediatric uveitis to tumor necrosis factor-alpha inhibitors[J]. J Rheumatol, 2013, 40(8): 1394-1403. DOI: 10.3899/jrheum.121180.
12.	Tynjala P, Kotaniemi K, Lindahl P, et al. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis[J]. Rheumatology (Oxford), 2008, 47(3): 339-344. DOI: 10.1093/rheumatology/kem356.
13.	Lamattina KC, Koreishi AF. What is new in paediatric uveitis?[J]. Curr Opin Ophthalmol, 2018, 29(5): 412-418. DOI: 10.1097/ICU.0000000000000501.
14.	Ghanma RA, Steeples L, Pockar S, et al. Adalimumab (ADA) in pediatric non-infectious uveitis: an observational study[J/OL]. Cureus, 2024, 16(4): e59019[2024-04-25]. https://pubmed.ncbi.nlm.nih.gov/38800327/. DOI: 10.7759/cureus.59019.
15.	Song H, Zhao C, Xiao J, et al. The efficacy and safety of Adalimumab in treating pediatric noninfectious chronic anterior uveitis with peripheral retinal vascular leakage: a pilot study[J/OL]. Front Med (Lausanne), 2022, 9: 813696[2022-03-29]. https://pubmed.ncbi.nlm.nih.gov/35425781/. DOI: 10.3389/fmed.2022.813696.
16.	Silvestri E, Bitossi A, Bettiol A, et al. Adalimumab effectively controls both anterior and posterior noninfectious uveitis associated with systemic inflammatory diseases: focus on Behçet's syndrome[J]. Inflammopharmacology, 2020, 28(3): 711-718. DOI: 10.1007/s10787-020-00697-4.
17.	Ruiz-Lozano RE, Mousa HM, Soifer M, et al. Adalimumab to treat noninfectious pediatric chronic anterior uveitis: a case series[J/OL]. Int Ophthalmol, 2024, 44(1): 376[2024-09-10]. https://pubmed.ncbi.nlm.nih.gov/39254907/. DOI: 10.1007/s10792-024-03289-1.
18.	Choe S, Heo JW, Oh BL. Quiescence and subsequent anterior chamber inflammation in Adalimumab-treated pediatric noninfectious uveitis[J]. Korean J Ophthalmol, 2020, 34(4): 274-280. DOI: 10.3341/kjo.2020.0005.
19.	Kouwenberg CV, Koopman-Kalinina AV, de Boer JH. Clinical benefits and potential risks of adalimumab in non-JIA chronic paediatric uveitis[J/OL]. Acta Ophthalmol, 2022, 100(4): e994-e1001[2021-09-16]. https://pubmed.ncbi.nlm.nih.gov/34532967/. DOI: 10.1111/aos.15012.
20.	Vitale A, Casa FD, 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[J]. Ophthalmol Ther, 2023, 12(4): 1957-1971. DOI: 10.1007/s40123-023-00712-1.
21.	Tao T, Yang S, He D, et al. The efficacy of Adalimumab in children with chronic non-infectious posterior uveitis and panuveitis: a retrospective cohort study[J]. Ophthalmol Ther, 2024, 13(5): 1239-1253. DOI: 10.1007/s40123-024-00884-4.

1. Maleki A, Anesi SD, Look-Why S, et al. Pediatric uveitis: a comprehensive review[J]. Surv Ophthalmol, 2022, 67(2): 510-529. DOI: 10.1016/j.survophthal.2021.06.006.
2. Sharon Y, Friling R, Luski M, et al. Uveitic glaucoma: long-term clinical outcome and risk factors for progression[J]. Ocul Immunol Inflamm, 2017, 25(6): 740-747. DOI: 10.1080/09273948.2016.1255341.
3. Ramanan AV, Dick AD, Jones AP, et al. Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis[J]. N Engl J Med, 2017, 376(17): 1637-1646. DOI: 10.1056/NEJMoa1614160.
4. Quartier P, Baptiste A, Despert V, et al. ADJUVITE: a double-blind, randomised, placebo- controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis[J]. Ann Rheum Dis, 2018, 77(7): 1003-1011. DOI: 10.1136/annrheumdis-2017-212089.
5. 海峡两岸医药卫生交流协会风湿免疫分会眼免疫学组. 抗肿瘤坏死因子-α单克隆抗体治疗非感染性葡萄膜炎中国专家共识[J]. 中华眼底病杂志, 2024, 40(1): 8-19. DOI: 10.3760/cma.j.cn511434-20231201-00473.Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association. Chinese expert consensus on treatment of non-infectious uveitis with anti-tumor necrosis factor-alpha monoclonal antibody[J]. Chin J Ocul Fundus Dis, 2024, 40(1): 8-19. DOI: 10.3760/cma.j.cn511434-20231201-00473.
6. Mccracken C, Yeh S, Jenkins K, et al. Timing of infliximab and adalimumab initiation despite methotrexate in children with chronic non-infectious anterior uveitis[J]. Eye (Lond), 2019, 33(4): 629-639. DOI: 10.1038/s41433-018-0283-0.
7. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop[J]. Am J Ophthalmol, 2005, 140(3): 509-516. DOI: 10.1016/j.ajo.2005.03.057.
8. Nussenblatt RB, Palestine AG, Chan CC, et al. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis[J]. Ophthalmology, 1985, 92(4): 467-471. DOI: 10.1016/s0161-6420(85)34001-0.
9. Touhami S, Diwo E, Seve P, et al. Expert opinion on the use of biological therapy in non-infectious uveitis[J]. Expert Opin Biol Ther, 2019, 19(5): 477-490. DOI: 10.1080/14712598.2019.1595578.
10. Jaffe GJ, Dick AD, Brezin AP, et al. Adalimumab in patients with active noninfectious uveitis[J]. N Engl J Med, 2016, 375(10): 932-943. DOI: 10.1056/NEJMoa1509852.
11. Lerman MA, Burnham JM, Chang PY, et al. Response of pediatric uveitis to tumor necrosis factor-alpha inhibitors[J]. J Rheumatol, 2013, 40(8): 1394-1403. DOI: 10.3899/jrheum.121180.
12. Tynjala P, Kotaniemi K, Lindahl P, et al. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis[J]. Rheumatology (Oxford), 2008, 47(3): 339-344. DOI: 10.1093/rheumatology/kem356.
13. Lamattina KC, Koreishi AF. What is new in paediatric uveitis?[J]. Curr Opin Ophthalmol, 2018, 29(5): 412-418. DOI: 10.1097/ICU.0000000000000501.
14. Ghanma RA, Steeples L, Pockar S, et al. Adalimumab (ADA) in pediatric non-infectious uveitis: an observational study[J/OL]. Cureus, 2024, 16(4): e59019[2024-04-25]. https://pubmed.ncbi.nlm.nih.gov/38800327/. DOI: 10.7759/cureus.59019.
15. Song H, Zhao C, Xiao J, et al. The efficacy and safety of Adalimumab in treating pediatric noninfectious chronic anterior uveitis with peripheral retinal vascular leakage: a pilot study[J/OL]. Front Med (Lausanne), 2022, 9: 813696[2022-03-29]. https://pubmed.ncbi.nlm.nih.gov/35425781/. DOI: 10.3389/fmed.2022.813696.
16. Silvestri E, Bitossi A, Bettiol A, et al. Adalimumab effectively controls both anterior and posterior noninfectious uveitis associated with systemic inflammatory diseases: focus on Behçet's syndrome[J]. Inflammopharmacology, 2020, 28(3): 711-718. DOI: 10.1007/s10787-020-00697-4.
17. Ruiz-Lozano RE, Mousa HM, Soifer M, et al. Adalimumab to treat noninfectious pediatric chronic anterior uveitis: a case series[J/OL]. Int Ophthalmol, 2024, 44(1): 376[2024-09-10]. https://pubmed.ncbi.nlm.nih.gov/39254907/. DOI: 10.1007/s10792-024-03289-1.
18. Choe S, Heo JW, Oh BL. Quiescence and subsequent anterior chamber inflammation in Adalimumab-treated pediatric noninfectious uveitis[J]. Korean J Ophthalmol, 2020, 34(4): 274-280. DOI: 10.3341/kjo.2020.0005.
19. Kouwenberg CV, Koopman-Kalinina AV, de Boer JH. Clinical benefits and potential risks of adalimumab in non-JIA chronic paediatric uveitis[J/OL]. Acta Ophthalmol, 2022, 100(4): e994-e1001[2021-09-16]. https://pubmed.ncbi.nlm.nih.gov/34532967/. DOI: 10.1111/aos.15012.
20. Vitale A, Casa FD, 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[J]. Ophthalmol Ther, 2023, 12(4): 1957-1971. DOI: 10.1007/s40123-023-00712-1.
21. Tao T, Yang S, He D, et al. The efficacy of Adalimumab in children with chronic non-infectious posterior uveitis and panuveitis: a retrospective cohort study[J]. Ophthalmol Ther, 2024, 13(5): 1239-1253. DOI: 10.1007/s40123-024-00884-4.

Chinese Journal of Ocular Fundus Diseases

The efficacy of Adalimumab in treatment of pediatric noninfectious uveitis and the factors influencing the efficacy

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