Table 1.
Structured Review of Methodology Employed in Cohort Studies Regarding Cancer Risk Associated with TNF Inhibitors
| Author, Year (reference) | Cohort Assembly; mean age or range | Comparator Group | Exposure Definition | Endpoint Definition | Covariates | Concurrent Medications | |
|---|---|---|---|---|---|---|---|
| Lag period (days) | Once exposed always exposed | Definition and data sources | |||||
| Askling, 2009* (20) | New TNFi users from the Swedish biologics registry (ARTIS); mean 64 years | New users of non-biologic DMARDs | None | Yes | First cancer in national registry, confirmed with chart review in over 50% of subjects, including NMSC | Sociodemographics; time dependent comorbidities; RA characteristics, disease duration | Separate analyses focused on concurrent MTX and other nonbiologic DMARDS |
| Askling, 2009* (18) | New TNFi users from the National RA Cohort linked to Swedish Biologics Register; mean 64 years | TNFi-naive RA patients | None | Yes | Lymphoma diagnosis in national registry | Age, gender, sociodemographics, comorbidities | No |
| Askling, 2005* (19) | New TNFi users from the Swedish biologics registry (ARTIS); range 16–75+ years | TNFi-naïve RA patients | None | Yes | Hematopoietic malignancies in national registry | Age, gender, disease duration | No |
| Bernatsky, 2008 (20) | Subjects with RA found in the Provincial administrative database from Quebec; mean 62 years | Non TNFi-users with RA | None | No | Lung cancer diagnosis from physician billing and hospitalization records | Age, sex andd calendar year matched controls. Concomitant DMARDs and glucocorticoids, number of physician visits, co-morbidities, and extra-articular disease | Yes |
| Bernatsky, 2008 (21) | Subjects with RA found in the Provincial administrative database from Quebec; mean 62 years | Non TNFi-users with RA | None | No | Hematologic malignant neoplasms from physician billing and hospitalization records | Age, sex andd calendar year matched controls. Concomitant DMARDs and glucocorticoids, number of physician visits, co-morbidities, and extra-articular disease | Yes |
| Chakavarty, 2005† (21) | TNFi users in National Data Bank for Rheumatic Diseases (NDB); unclear if new or prevalent users; mean 63 years | TNFi-naïve RA patients | Not specified | Not specified | New NMSC confirmed by interview with patient | Age, gender, sociodemographics, disease duration, RA characteristics, smoking, NMSC prior to enrolling, prednisione, leflunomide, MTX (with and without TNFi) | Yes |
| Geborek, 2005 (22) | New TNFi users in the SSATG register; mean 60 years | TNFi-naïve RA patients in prevalent community based cohort | None | Yes | SSATG linkage to regional cancer registry, including cutaneous cancers | RA characteristics | No |
| Setoguchi, 2007 (23) | New biologic DMARD users from Medicare or British Columbia; mean 73 years | New MTX users in an RA cohort | 180 days | Yes | Diagnosis and procedure codes in healthcare claims database, including melanoma | Age, gender, RA characteristics | Yes |
| Wolfe, 2007† (25) | TNFi users from the NDB; unclear if new or prevalent‡; mean 59 years | Non TNFi treated patients in NDB | None | Yes | Lymphoma based on hospital and/or physician reports or death certificates | Age, gender, sociodemographics, comorbidities, smoking, RA characteristics, prednisone, and number of prior DMARDs | Yes |
| Wolfe, 2007† (24) | TNFi users from NDB; unclear if new or prevalent‡; mean 59 years | Non TNFi treated patients in NDB | 180 days | Yes | Patient questionnaire, interview, and medical record review, including melanoma and NMSC | Age, gender, sociodemographics, comorbidities, smoking, RA characteristics, prednisone | Yes |
| Dixon, 2010 (35) | TNFi users from the BSRBR; mean 64 years | Non TNFi treated patients in BSRBR | None | Yes | Linkage to national cancer registry, excluding NMSC and CIS | Age, sex, RA characteristics, disease duration, year of entry, and smoking status | Yes |
Abbreviations: MTX, methotrexate; RA, rheumatoid arthritis; TNFi, tumor necrosis factor inhibitor; NMSC, non-melanoma skin cancer; CIS, carcinoma in situ; NDB, National Data Bank for Rheumatic Diseases; BSRBR, British Society for Rheumatology Biologics Register
*
These studies all used data from the same population, although the specific cohort design varied.
†
These studies all used data from the National Data Bank for Rheumatic Diseases (NDB)
‡
While Wolfe’s studies are performed in a cohort setting, analysis was done as if they were nested case-control studies. Analysis for these studies was done nested case-control studies.
**
Bernatsky’s studies were both nested case-control studies.