Case reportLung cancer after exposure to disease modifying anti-rheumatic drugs
Section snippets
Methods
We assembled a cohort of RA patients using provincial administrative data from the Régie d’assurance maladie du Québec [RAMQ] physician billing and pharmacy claims databases, and the provincial hospitalization database. The RAMQ and hospitalization databases are linkable through use of provincial health insurance numbers, a 10-digit unique identifier for each beneficiary.
Physician services and inpatient medical care are covered by universal provincial health insurance, but the pharmacy database
Data analysis
Conditional logistic regression was used to estimate, in the nested case-control sample, the rate ratio (RR) for lung cancer related to each DMARD, along with 95% confidence intervals (CIs) for the adjusted estimates. For our analyses we considered DMARD exposures in terms of time-dependent use, aiming to assess the independent effects of the most commonly used types. The adjusted RR estimate reflects the impact of each specific exposure, adjusted for all other medications, as well as
Results
The study cohort included 23,810 RA patients with DMARD exposures and no prior history of cancer. At the time of entry into the cohort, the average age of subjects was 61.7 (standard deviation [S.D.] = 14.6) years. The majority (70.1%) were women, reflecting the typical female predominance in RA. The most commonly used DMARDs at cohort entry included methotrexate, anti-malarial agents, and sulfasalazine.
Subjects were followed for a total of 157,204 person-years (an average of 6.7 years, S.D. 5.1,
Discussion
Though most studies of malignancy in RA have focussed on the risk of hematological malignancy, there is also growing evidence of increased lung cancer risk, both in terms of incidence [1], [8] and mortality [2]. Given the importance of lung cancer in RA, it is somewhat surprising that there has been little effort to establish the etiology of the association.
One potential explanation has been that cancer risk in RA is driven by drug exposures, particularly alkylating agents like
Conflict of interest
None.
Acknowledgements
Sasha Bernatsky is the recipient of career awards from the Canadian Institutes for Health Research (CIHR), Fonds de recherche en santé du Québec (FRSQ), Canadian Arthritis Network, and of support from the McGill University Research Institute and Faculty of Medicine. Ann Clarke is an FRSQ National Scholar. Samy Suissa is the recipient of the James McGill professorship and the CIHR distinguished investigator award. The McGill Pharmacoepidemiology Research Unit is funded by the FRSQ.
References (18)
- et al.
Rheumatoid arthritis and cancer risk
Eur J Cancer
(1996) - et al.
Effect of preoperative delay on survival in patients with bladder cancer undergoing cystectomy in Quebec: a population based study
J Urol
(2006) - et al.
The extra-articular features of rheumatoid arthritis: a systematic analysis of 127 cases
Am J Med
(1973) - et al.
Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Long-term case-control follow-up study
Am J Med
(1987) - et al.
Association between glutathione S-transferase p1 polymorphisms and lung cancer risk in Caucasians: a case-control study
Lung Cancer
(2003) - et al.
Cigarette smoking and rheumatoid arthritis
Semin Arthritis Rheum
(2001) - et al.
Lung cancer associated with rheumatoid arthritis does not shorten life expectancy
J Chin Med Assoc
(2005) - et al.
National study of cause-specific mortality in rheumatoid arthritis, juvenile chronic arthritis, and other rheumatic conditions: a 20-year follow-up study
J Rheumatol
(2003) - et al.
Factors associated with pattern of care before surgery for breast cancer in Quebec between 1992 and 1997
Med Care
(2003)
Cited by (16)
The incidence and prognosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of the lung related to methotrexate: A retrospective study
2024, Pulmonary Pharmacology and Therapeutics2020 guide for the diagnosis and treatment of interstitial lung disease associated with connective tissue disease
2021, Respiratory InvestigationCitation Excerpt :CS pulse therapy is often repeated until the condition stabilizes. Additional treatment with immunosuppressants should be considered for severe or refractory cases [123]. It is important to continue studying the diagnosis and management of RA-ILD because of the lack of evidence.
Rheumatoid arthritis and risk of lung cancer: Meta-analysis and Mendelian randomization study
2021, Seminars in Arthritis and RheumatismCitation Excerpt :The cancer risk of a cohort study of UK patients with RA was increased by 65% by immunosuppressants exposure, and the risk appears to be related to the dose used [69]. Another cohort study from Canada did not suggest that DMARDs exposures are the primary mediator of LC risk in RA [70]. A clear need exists for ongoing research into the safety across all DMARD therapies concerning malignancies.
Summary of the Japanese Respiratory Society statement for the treatment of lung cancer with comorbid interstitial pneumonia
2019, Respiratory InvestigationCitation Excerpt :the cancerous lesions were frequently seen at a peripheral site. Multiple primary types of cancer were frequently seen in autopsy cases and often developed as small-cell carcinomas [18,20]. There are many other reports with similar findings (Table 2), and it is generally thought that lung cancers develop frequently at fibrotic sites in the lower lobe.
Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review
2018, European Journal of Medicinal ChemistryCitation Excerpt :Case reports have linked MTX to different types of cancers, which are mainly lymphomas and pseudo lymphomas [133,149,151,223,265–275]. Currently, there is no certain evidence to confirm the oncogenicity effects of MTX [142,276], because the autoimmune pathogenesis of RA may in part contribute to the risk of cancer among patients with RA [277–279]. Genetic factors, smoking-related tissue necrosis and viral infections are all common etiology between RA, cancer and MTX [278,280–282].
Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs
2014, Seminars in Arthritis and Rheumatism