Effectiveness of Frequently Used TNF Inhibitors vs. Conventional Immunosuppressive Therapies for Noninfectious Uveitis

Sapna S Gangaputra¹, Craig W Newcomb², Gui-Shuang Ying³, Kurt A Dreger^{3

4}, Tonetta Fitzgerald³, Pichaporn Artornsombudh^{5

6}, Srishti Kothari^{3

7}, Teresa L Liesegang⁸, James T Rosenbaum^{8

9}, H Nida Sen¹⁰, Eric B Suhler^{8

11

12}, Jennifer E Thorne^{13

14}, Nirali P Bhatt³, C Stephen Foster¹⁵, Douglas A Jabs^{13

16}, Grace A Levy-Clarke^{10

17}, Careen Y Lowder¹⁸, Debra A Goldstein¹⁹, Gary N Holland²⁰, Glenn J Jaffe²¹, Janet L Davis²², Nisha R Acharya²³, Paul A Latkany²⁴, Russell W Read²⁵, Sunir J Garg²⁶, Yannek I Liederman¹⁹, Jeanine M Buchanich²⁷, John H Kempen^{7

28

29

30

31}, For The Systemic Immunosuppressive Therapy For Eye Diseases Site Cohort Study Research Group

Affiliations

¹ Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
² Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, The Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ Department of Ophthalmology, The Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Department of Population, Family, and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵ Department of Ophthalmology, Somdech Phra Pinklao Hospital, Royal Thai Navy, Bangkok, Thailand.
⁶ Department of Ophthalmology, Chulalongkorn University, Bangkok, Thailand.
⁷ Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon, USA.
⁹ Legacy Devers Eye Institute, Portland, Oregon, USA.
¹⁰ Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹¹ Department of Ophthalmology, Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
¹² Oregon Health and Science University- Portland State University School of Public Health, Portland, Oregon, USA.
¹³ Department of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁴ Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
¹⁵ Massachusetts Eye Research and Surgery Institution, Waltham, Massachusetts, USA.
¹⁶ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
¹⁷ Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, West Virginia, USA.
¹⁸ Department of Ophthalmology Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁹ Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
²⁰ Department of Ophthalmology, Ocular Inflammatory Disease Center, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
²¹ Department of Ophthalmology, Duke University, Durham, North Carolina, USA.
²² Department of Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, USA.
²³ Department of Ophthalmology, F.I. Proctor Foundation, University of California San Francisco School of Medicine, San Francisco, California, USA.
²⁴ Department of Ophthalmology, New York Eye and Ear Infirmary/Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
²⁵ Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²⁶ Mid-Atlantic Retina, The Retina Service of Wills Eye Hospital, Philadelphia, Pennsylvania, USA.
²⁷ School of Public Health, Center for Occupational Biostatistics and Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²⁸ Department of Ophthalmology and Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
²⁹ Department of Ophthalmology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
³⁰ MCM Eye Unit, MyungSung Christian Medical Center (MCM) Comprehensive Specialized Hospital and MyungSung Medical College, Addis Ababa, Ethiopia.
³¹ Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 40233243
PMCID: PMC12286736 (available on 2026-04-15)
DOI: 10.1080/09273948.2025.2479802

Comparative Study

Effectiveness of Frequently Used TNF Inhibitors vs. Conventional Immunosuppressive Therapies for Noninfectious Uveitis

Sapna S Gangaputra et al. Ocul Immunol Inflamm. 2025 Aug.

. 2025 Aug;33(6):948-956.

doi: 10.1080/09273948.2025.2479802. Epub 2025 Apr 15.

Authors

Affiliations

¹ Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
² Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, The Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ Department of Ophthalmology, The Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Department of Population, Family, and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵ Department of Ophthalmology, Somdech Phra Pinklao Hospital, Royal Thai Navy, Bangkok, Thailand.
⁶ Department of Ophthalmology, Chulalongkorn University, Bangkok, Thailand.
⁷ Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon, USA.
⁹ Legacy Devers Eye Institute, Portland, Oregon, USA.
¹⁰ Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹¹ Department of Ophthalmology, Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
¹² Oregon Health and Science University- Portland State University School of Public Health, Portland, Oregon, USA.
¹³ Department of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁴ Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
¹⁵ Massachusetts Eye Research and Surgery Institution, Waltham, Massachusetts, USA.
¹⁶ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
¹⁷ Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, West Virginia, USA.
¹⁸ Department of Ophthalmology Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁹ Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
²⁰ Department of Ophthalmology, Ocular Inflammatory Disease Center, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
²¹ Department of Ophthalmology, Duke University, Durham, North Carolina, USA.
²² Department of Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, USA.
²³ Department of Ophthalmology, F.I. Proctor Foundation, University of California San Francisco School of Medicine, San Francisco, California, USA.
²⁴ Department of Ophthalmology, New York Eye and Ear Infirmary/Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
²⁵ Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²⁶ Mid-Atlantic Retina, The Retina Service of Wills Eye Hospital, Philadelphia, Pennsylvania, USA.
²⁷ School of Public Health, Center for Occupational Biostatistics and Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²⁸ Department of Ophthalmology and Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
²⁹ Department of Ophthalmology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
³⁰ MCM Eye Unit, MyungSung Christian Medical Center (MCM) Comprehensive Specialized Hospital and MyungSung Medical College, Addis Ababa, Ethiopia.
³¹ Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 40233243
PMCID: PMC12286736 (available on 2026-04-15)
DOI: 10.1080/09273948.2025.2479802

Abstract

Purpose: To compare the corticosteroid sparing efficacy of frequently used antimetabolites to tumor necrosis factor (TNF) inhibitors in the management of noninfectious ocular inflammation.

Methods: Retrospective analysis of patients with noninfectious uveitis on conventional antimetabolite (methotrexate, mycophenolate mofetil, azathioprine,or leflunomide, "CONV") or a TNF inhibitor (adalimumab or infliximab, "TNFi") with active inflammation or more than 7.5 mg daily prednisone. Eyes were assessed in three groups: CONV only, TNFi only and combination of both (COMB). Cox regression models compared treatment success, adjusted for age, race, smoking, anatomic location of uveitis, duration of uveitis and visual acuity. Corticosteroid sparing success was defined as: inactive or slightly active uveitis on <=7.5 mg daily oral prednisone and <=2 drops of prednisolone acetate 1%.

Results: There were 1475 eligible patients in the analysis. By 6 and 12 months, respectively, the Cox model-predicted, percentage success was 27.6% and 44.9% for the CONV group; 34.2% and 53.9% in the TNFi group and 39.9% and 61.1% for the COMB group. COMB was more likely than CONV to achieve success (adjusted HR 1.58 (95% confidence interval (CI), 1.28, 1.95, p < 0.0001). Factors associated with lower success were age under 18 years, smoking, visual acuity worse than 20/50 at cohort entry, over 4-year duration of uveitis and daily baseline prednisone 7.5 mg or higher (all p < 0.05).

Conclusion: Our results suggest COMB is more effective than CONV at achieving disease quiescence and corticosteroid sparing success among patients with active noninfectious uveitis. More research is needed to determine if TNFi alone is superior to CONV for uveitic corticosteroid-sparing.

Keywords: Antimetabolites; TNF inhibitor; immunosuppression; uveitis.

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References

1. 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. Apr;149(4):550–561.e10. - PMC - PubMed
1. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Louis TA, Sugar EA, Thorne JE. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology. 2011. Oct;118(10):1916–26. - PMC - PubMed
1. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen JH, Altaweel MM, Drye LT, Holbrook JT, Jabs DA, Sugar EA, Thorne JE. Benefits of Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, and Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. Ophthalmology. 2015. Oct;122(10):1967–75. - PMC - PubMed
1. Writing Committee for the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group; Kempen JH, Altaweel MM, Holbrook JT, Sugar EA, Thorne JE, Jabs DA. Association Between Long-Lasting Intravitreous Fluocinolone Acetonide Implant vs Systemic Anti-inflammatory Therapy and Visual Acuity at 7 Years Among Patients With Intermediate, Posterior, or Panuveitis. JAMA. 2017. May 16;317(19):1993–2005. - PMC - PubMed
1. Kempen JH, Daniel E, Gangaputra S, Dreger K, Jabs DA, Kaçmaz RO, Pujari SS, Anzaar F, Foster CS, Helzlsouer KJ, Levy-Clarke GA, Nussenblatt RB, Liesegang T, Rosenbaum JT, Suhler EB. Methods for identifying long-term adverse effects of treatment in patients with eye diseases: the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Ophthalmic Epidemiol. 2008. Jan-Feb;15(1):47–55. - PubMed

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Effectiveness of Frequently Used TNF Inhibitors vs. Conventional Immunosuppressive Therapies for Noninfectious Uveitis

Affiliations

Effectiveness of Frequently Used TNF Inhibitors vs. Conventional Immunosuppressive Therapies for Noninfectious Uveitis

Authors

Affiliations

Abstract

References

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LinkOut - more resources

Full Text Sources

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