title: Malignancy risk in patients with inflammatory eye disease treated with systemic immunosuppressive therapy: a tertiary referral cohort study.
abstract: OBJECTIVE
  To ascertain whether patients on long-term systemic immunosuppressive therapy for inflammatory eye disease (IED) are at increased risk of malignancy.
  
  
  METHODS
  A single-center, retrospective cohort study.
  
  
  METHODS
  We included 190 adults with IED treated with corticosteroids only (n = 58) or systemic immunosuppression (n = 132) for ≥6 months between 1985 and 2007. Immunosuppressed patients were treated with antimetabolites, T-cell inhibitors, and/or alkylating agents.
  
  
  METHODS
  Incident malignancies were ascertained by self-report and confirmed by medical record review. Multiple malignancies in a single patient were counted, except for nonmelanoma skin cancer (NMSC), where only the first was counted. Standardized incidence ratios (SIRs) were calculated by malignancy type. Cox regression models were used to compare malignancy incidence by treatment type.
  
  
  METHODS
  Risk of malignancy relative to the general population and within the cohort.
  
  
  RESULTS
  During a median 7.34 years of follow-up, 25 malignancies were observed in 17 patients, namely, 2.10 per 100 person-years and 0.43 per 100 person-years in the immunosuppressed and corticosteroid only groups, respectively. In the immunosuppressed group, the most common malignancies were NMSC (n = 11) and non-Hodgkin's lymphoma (NHL; n = 4) and malignancy risk was significantly increased compared with the general population for any malignancy (SIR, 4.39; 95% CI, 2.78-6.59) and for any malignancy excluding NMSC (SIR, 4.16; 95% CI, 1.67-8.57). Significantly elevated SIRs were observed for NMSC and NHL in those treated with immunosuppressive agents. Compared with the corticosteroid treatment-only group, the immunosuppressed group was at an increased risk of any malignancy (adjusted hazard ratio, 4.36; 95% CI, 1.02-18.7), but not first malignancy (n = 17; adjusted hazard ratio, 2.56; 95% CI, 0.57-11.5). No cancer-related deaths were observed.
  
  
  CONCLUSIONS
  Our findings suggest that patients with IED treated with systemic immunosuppressive therapy are at increased risk of malignancy; however, the increase in absolute risk was modest. The types of malignancies observed at excess risk are similar to those observed in solid organ transplant recipients and patients with autoimmune diseases treated with systemic immunosuppression. Immunosuppressive therapy remains an important treatment modality in IED; however, patients may benefit from targeted malignancy-prevention strategies and long-term clinical follow-up. These findings require validation by a prospective, long-term, population-based cohort study.
authors.affiliation: Ocular inflammation Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia; Department of Ophthalmology, St Vincent's Hospital, Darlinghurst, Sydney, Australia. Electronic address: yates.willb@gmail.com.
authors.forename: William B
authors.initials: WB
authors.lastname: Yates
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Renhua
authors.initials: R
authors.lastname: Na
authors.affiliation: Ocular inflammation Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia; Department of Ophthalmology, St Vincent's Hospital, Darlinghurst, Sydney, Australia; Save Sight Institute, Sydney Eye Hospital, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCluskey
authors.affiliation: Ocular inflammation Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia; Department of Ophthalmology, St Vincent's Hospital, Darlinghurst, Sydney, Australia.
authors.forename: Denis
authors.initials: D
authors.lastname: Wakefield
mesh_terms: D000328:Adult; D000477:Alkylating Agents / Q000009:adverse effects / Q000627:therapeutic use; D000963:Antimetabolites / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D010390:Pemphigoid, Benign Mucous Membrane / Q000188:drug therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D015423:Scleritis / Q000188:drug therapy*; D062606:Tertiary Care Centers; D014605:Uveitis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000477:Alkylating Agents; D000963:Antimetabolites; D005938:Glucocorticoids; D007166:Immunosuppressive Agents