. 2023 Aug 21;2(1):e000037.

doi: 10.1136/bmjonc-2023-000037. eCollection 2023.

Use of immunosuppression and subsequent cancer incidence: cohort study

Jeanine M Buchanich¹, Craig W Newcomb², Terri L Washington¹, Charles Stephen Foster^{3

4}, Lucia Sobrin^{4

5}, Jennifer E Thorne^{6

7}, Douglas Alan Jabs^{6

7}, Eric B Suhler^{8

9}, James T Rosenbaum^{8

10

11}, Hatice Nida Sen^{12

13}, Grace A Levy-Clarke¹⁴, Robert B Nussenblatt¹⁵, Nirali P Bhatt¹⁶, Careen Y Lowder¹⁷, Debra A Goldstein¹⁸, Yannek I Leiderman¹⁹, Nisha R Acharya²⁰, Gary N Holland²¹, Russell W Read²², James P Dunn²³, Kurt A Dreger²⁴, Pichaporn Artornsombudh²⁵, Hosne A Begum⁶, Tonetta D Fitzgerald¹⁶, Srishti Kothari^{5

16}, Abhishek R Payal²⁶, Ebenezer Daniel¹⁶, Sapna S Gangaputra²⁷, Roje Oktay Kaçmaz²⁸, Teresa L Liesegang⁸, Siddharth S Pujari²⁹, Naira Khachatryan¹⁶, Armin Maghsoudlou³⁰, Hilkiah K Suga^{31

32}, Clara M Pak^{32

33}, Kathy J Helzlsouer⁷, John H Kempen^{4

31

32

34

35

36}

Affiliations

¹ Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
² Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ Massachusetts Eye Research and Surgery Institution, Boston, Massachusetts, USA.
⁴ Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA.
⁵ Department of Ophthalmology and Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁷ Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁸ Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon, USA.
⁹ Portland Veteran's Affairs Medical Center, Portland, Oregon, USA.
¹⁰ Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
¹¹ Legacy Devers Eye Institute, Portland, Oregon, USA.
¹² Department of Ophthalmology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
¹³ Janssen Retina Global Clinical Development, Princeton, New Jersey, USA.
¹⁴ Department of Ophthalmology and Visual Sciences, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
¹⁵ Laboratory of Immunology, National Eye Institute, Bethesda, Maryland, USA.
¹⁶ Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹⁷ Cole Eye Institute, Department of Ophthalmology, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁸ Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁹ Illinois Eye & Ear Infirmary, Department of Ophthalmology and Visual Sciences, University of Illinois Chicago College of Medicine, Chicago, Illinois, USA.
²⁰ F.I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA.
²¹ Ocular Inflammatory Disease Center, Jules Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, Los Angeles, California, USA.
²² Department of Ophthalmology and Visual Sciences, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.
²³ Mid-Atlantic Retina, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.
²⁴ Department of Population, Family, and Reproductive Health, Johns Hopkins University, Baltimore, Maryland, USA.
²⁵ Department of Ophthalmology, Somdech Phra Pinkloa Hospital, Royal Thai Navy, Bangkok, Thailand.
²⁶ Mahatme EyeBank Eye Hospital, Nagpur, Maharashtra, India.
²⁷ Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁸ Santen Pharmaceutical Co Ltd, Emeryville, California, USA.
²⁹ Siddharth Netralaya Superspecialty Eye Hospital, Belgaum, Karnataka, India.
³⁰ Neurology, Northwell Health, Staten Island, New York, USA.
³¹ MyungSung Medical College, Addis Ababa, Addis Ababa, Ethiopia.
³² MCM Eye Unit, MyungSung Christian Medical Center (MCM) General Hospital and MyungSung Medical School, Addis Ababa, Addis Ababa, Ethiopia.
³³ University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
³⁴ Sight for Souls, Bellevue, Washington, USA.
³⁵ Department of Ophthalmology, Addis Ababa University School of Medicine, Addis Ababa, Ethiopia.
³⁶ Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 39886503
PMCID: PMC11203086
DOI: 10.1136/bmjonc-2023-000037

Use of immunosuppression and subsequent cancer incidence: cohort study

Jeanine M Buchanich et al. BMJ Oncol. 2023.

. 2023 Aug 21;2(1):e000037.

doi: 10.1136/bmjonc-2023-000037. eCollection 2023.

Authors

Affiliations

¹ Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
² Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ Massachusetts Eye Research and Surgery Institution, Boston, Massachusetts, USA.
⁴ Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA.
⁵ Department of Ophthalmology and Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁷ Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁸ Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon, USA.
⁹ Portland Veteran's Affairs Medical Center, Portland, Oregon, USA.
¹⁰ Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
¹¹ Legacy Devers Eye Institute, Portland, Oregon, USA.
¹² Department of Ophthalmology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
¹³ Janssen Retina Global Clinical Development, Princeton, New Jersey, USA.
¹⁴ Department of Ophthalmology and Visual Sciences, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
¹⁵ Laboratory of Immunology, National Eye Institute, Bethesda, Maryland, USA.
¹⁶ Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹⁷ Cole Eye Institute, Department of Ophthalmology, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁸ Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁹ Illinois Eye & Ear Infirmary, Department of Ophthalmology and Visual Sciences, University of Illinois Chicago College of Medicine, Chicago, Illinois, USA.
²⁰ F.I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA.
²¹ Ocular Inflammatory Disease Center, Jules Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, Los Angeles, California, USA.
²² Department of Ophthalmology and Visual Sciences, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.
²³ Mid-Atlantic Retina, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.
²⁴ Department of Population, Family, and Reproductive Health, Johns Hopkins University, Baltimore, Maryland, USA.
²⁵ Department of Ophthalmology, Somdech Phra Pinkloa Hospital, Royal Thai Navy, Bangkok, Thailand.
²⁶ Mahatme EyeBank Eye Hospital, Nagpur, Maharashtra, India.
²⁷ Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁸ Santen Pharmaceutical Co Ltd, Emeryville, California, USA.
²⁹ Siddharth Netralaya Superspecialty Eye Hospital, Belgaum, Karnataka, India.
³⁰ Neurology, Northwell Health, Staten Island, New York, USA.
³¹ MyungSung Medical College, Addis Ababa, Addis Ababa, Ethiopia.
³² MCM Eye Unit, MyungSung Christian Medical Center (MCM) General Hospital and MyungSung Medical School, Addis Ababa, Addis Ababa, Ethiopia.
³³ University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
³⁴ Sight for Souls, Bellevue, Washington, USA.
³⁵ Department of Ophthalmology, Addis Ababa University School of Medicine, Addis Ababa, Ethiopia.
³⁶ Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 39886503
PMCID: PMC11203086
DOI: 10.1136/bmjonc-2023-000037

Abstract

Objective: Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID).

Methods and analysis: We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began.

Results: The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence.

Conclusions: We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence.

Trial registration number: NCT00116090.

Keywords: epidemiology; immunomodulation.

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Conflict of interest statement

Competing interests: JHK: Betaliq (equity owner); Tarsier Pharma (equity owner). CSF: Aldeyra (consultant, grant support), Allakos (consultant), Bausch & Lomb (consultant, grant support), Eyegate (consultant, grant support, stock), Genentech (consultant), Novartis (consultant, grant support), pSivida (consultant, grant support), Aciont (grant support), Alcon (grant support, lecture fees), Clearside (grant support), Dompé (grant support), Mallinckrodt (grant support, lecture fees), Allergan (lecture fees). JTR: AbbVie (consultant); Gilead (consultant); Janssen (consultant); Eyevensys (consultant); UpToDate (consultant); Pfizer (financial support); Novartis (consultant); Roche (consultant); Alcon Research Institute (financial support); UCB (consultant); Horizon (consultant and finanicial support); Santen (consultant). GAL-C: AbbVie (consultant, lecture fees); Allergan (grant support); Mallinckrodt (consultant, grant support); Sanofi (grant support; lecture fees). EBS: Eyevensys (consultant); Santen (consultant); EyeGate (consultant, financial support); AbbVie (consultant, financial support); Clearside (consultant, financial support); EyePoint (consultant, financial support). JET: AbbVie (consultant); Canfield (consultant); Clearside (consultant); Gilead (consultant); Guidepoint (consultant); Roche (consultant); Tarsier Pharma (Scientific Advisory Board; equity owner); UptoDate (consultant). YIL: Research to Prevent Blindness (grant); Alcon (consultant); Microsurgical Guidance Solutions (equity owner); patents pending: WO2020163845 and USSN: 63/183424. HNS: Janssen (employee). ROK: Santen (employee).

Figures

**Figure 1**
Forest Plot of All Cancer Hazards, Including and Excluding Patients with Systemic Disease. TNF, tumour necrosis factor.

See this image and copyright information in PMC

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Gangaputra SS, Newcomb CW, Ying GS, Dreger KA, Fitzgerald T, Artornsombudh P, Kothari S, Liesegang TL, Rosenbaum JT, Sen HN, Suhler EB, Thorne JE, Bhatt NP, Foster CS, Jabs DA, Levy-Clarke GA, Lowder CY, Goldstein DA, Holland GN, Jaffe GJ, Davis JL, Acharya NR, Latkany PA, Read RW, Garg SJ, Liederman YI, Buchanich JM, Kempen JH, For The Systemic Immunosuppressive Therapy For Eye Diseases Site Cohort Study Research Group. Gangaputra SS, et al. Ocul Immunol Inflamm. 2025 Aug;33(6):948-956. doi: 10.1080/09273948.2025.2479802. Epub 2025 Apr 15. Ocul Immunol Inflamm. 2025. PMID: 40233243

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Use of immunosuppression and subsequent cancer incidence: cohort study

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Use of immunosuppression and subsequent cancer incidence: cohort study

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