Pauline Raaschou, MD, PhD; Jonas Söderling, MSE, PhD; Carl Turesson, MD (Professor); Johan Askling, MD (Professor); for the ARTIS Study Group *
Note: All authors, external and internal, had full access to all of the data.
Financial Support: By ALF (agreement concerning medical education and research in health and medical care in Stockholm County Council), the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Swedish Research Council.
Disclosures: The ARTIS Study Group conducts scientific analyses using data from the Swedish biologics register ARTIS (run by the Swedish Society for Rheumatology), which has entered into agreements with AbbVie, Bristol-Myers Squibb, Lilly, Merck, Pfizer, Roche, Samsung, and UCB. Dr. Söderling reports personal fees from Pfizer, AbbVie, Merck, Novartis, and Shire outside the submitted work. Dr. Turesson reports grants and personal fees from Bristol-Myers Squibb, Roche, and AbbVie and personal fees from Pfizer and Novartis outside the submitted work. Dr. Askling reports grants from AbbVie, Bristol-Myers Squibb, Lilly, Merck, Pfizer, Roche, Samsung Bioepis, UCB, the Swedish Cancer Society, Stockholm County Council (ALF), the Swedish Research Council, and the Swedish Foundation for Strategic Research during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2812.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Raaschou (e-mail, firstname.lastname@example.org).
Corresponding Author: Pauline Raaschou, MD, PhD, Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, T2:01, SE-171 76 Stockholm, Sweden; e-mail, email@example.com.
Current Author Addresses: Drs. Raaschou, Söderling, and Askling: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, T2:01, SE-171 76 Stockholm, Sweden.
Dr. Turesson: Department of Rheumatology, Skåne University Hospital, Inga-Marie Nilssons Gata 32, 205 02 Malmö, Sweden.
Author Contributions: Conception and design: P. Raaschou, J. Askling.
Analysis and interpretation of the data: P. Raaschou, J. Söderling, C. Turesson, J. Askling.
Drafting of the article: P. Raaschou.
Critical revision of the article for important intellectual content: P. Raaschou, J. Söderling, C. Turesson, J. Askling.
Final approval of the article: P. Raaschou, J. Söderling, C. Turesson, J. Askling.
Provision of study materials or patients: J. Askling.
Statistical expertise: P. Raaschou, J. Söderling, J Askling.
Obtaining of funding: J. Askling.
Administrative, technical, or logistic support: J. Askling.
Collection and assembly of data: P. Raaschou, J. Söderling, J. Askling.
Use of tumor necrosis factor inhibitors (TNFi) in patients with a history of cancer remains a clinical dilemma.
To investigate whether TNFi treatment in rheumatoid arthritis (RA) is associated with increased risk for cancer recurrence.
Population-based cohort study based on linkage of nationwide registers.
Patients with RA who started TNFi treatment between 2001 and 2015, after being diagnosed with cancer, and matched patients with RA and a history of the same cancer who had never received biologics.
The primary outcome was the first recurrence of cancer. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs), taking into account time, cancer type, and whether the cancer was invasive or in situ (or tumor, node, metastasis [TNM] classification system stage in a subset of patients).
Among 467 patients who started TNFi treatment (mean time after cancer diagnosis, 7.9 years), 42 had cancer recurrences (9.0%; mean follow-up, 5.3 years); among 2164 matched patients with the same cancer history, 155 had recurrences (7.2%; mean follow-up, 4.3 years) (HR, 1.06 [95% CI, 0.73 to 1.54). Hazard ratios were close to 1 in analyses of patient subsets matched on cancer stage or with similar time from index cancer diagnosis to the start of TNFi treatment, as well as in unmatched analyses. Several CIs had upper limits close to 2.
The outcome algorithm was partly nonvalidated, and channeling bias was possible if patients with a better index cancer prognosis were more likely to receive TNFi.
The findings suggest that TNFi treatment is not associated with increased risk for cancer recurrence in patients with RA, although meaningful risk increases could not be ruled out completely.
ALF (an agreement in Stockholm County Council concerning medical education and research in health and medical care), the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Swedish Research Council.
Raaschou P, Söderling J, Turesson C, Askling J, for the ARTIS Study Group. Tumor Necrosis Factor Inhibitors and Cancer Recurrence in Swedish Patients With Rheumatoid Arthritis: A Nationwide Population-Based Cohort Study. Ann Intern Med. [Epub ahead of print 14 August 2018]169:291–299. doi: 10.7326/M17-2812
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Published: Ann Intern Med. 2018;169(5):291-299.
Published at www.annals.org on 14 August 2018
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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