News & Perspective

Biologic use not associated with an increased risk of second malignancy in RA patients

1 year ago, OP Editor

The safety of biologics for the treatment of rheumatoid arthritis (RA) has been carefully studied for the past 15 years, however, there is still a concern that these medications, which suppress the immune system, could increase the risk of developing a second malignancy in patients with a history of cancer.1 New findings presented by Dr. Lene Dreyer, Associate Professor of Rheumatology at the University of Copenhagen, has provided reassurance regarding the above concern at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting.1

Biologic disease-modifying antirheumatic drugs (bDMARDs) have revolutionized the treatment of RA. The targeted suppression of key inflammatory pathways that give rise to RA symptoms and subsequent joint damage has allowed the better control of disease.2 However, the flip side of the coin is that treatment of bDMARDs may render patients more susceptible to malignancy by inducing certain extent of immunosuppression.3 While the overall cancer risk was previously demonstrated to be indifferent among those treated with bDMARDs and conventional synthetic DMARDs in a Swedish national cohort,3 there are limited data on the risk of cancer recurrence or a second primary tumor in patients with a prior malignancy.4 With the increasing number of long-term cancer survivors, Dr. Dreyer recognized second malignancy as an increasing challenge for both physicians and patients to reach consensus when formulating treatment plans for RA.5

“The concern for second malignancy or cancer recurrences in patients with a history of cancer diagnosis has led to some reluctance in treating this subset of arthritis patients with biologics, especially TNF-inhibitors. Consequently, some RA patients with a previous cancer are suffering from inadequate treatment of their arthritis,” said Dr. Dreyer.5

To study the risk of second malignancy in patients treated with bDMARDs, Dr. Dreyer and colleagues assessed a total of 1,678 RA patients who had a primary cancer diagnosis according to the DANBIO Registry, a national medical record database in Denmark, from 2000 to 2011. The rates for second malignant neoplasms (SMN) and death among biologic-experienced (n=502) and biologic-naïve patients (n=1,176) were compared and analysed.1

The findings were mostly reassuring. Treatment with bDMARDs, regardless of the time of treatment initiation, was not associated with an increased risk of SMN in patients with a history of cancer, as compared to those who were never treated with bDMARDs (Table 1).1


Meanwhile, the mortality rates among patients were also assessed, but the authors were unable to draw a clear conclusion about significant increases.1 For patients treated with bDMARDs only before the primary cancer diagnosis, the hazard ratio (HR) of death was 1.50 (95% CI: 1.15-1.97), but became 1.20 (95% CI: 0.88-1.63) following further adjustment for extent of the primary cancer.1

“Our data does provide some reassurance that biologics do not pose an immediate danger in patients with a history of cancer,” Dr. Dreyer explained, “however, the number of patients who suffered from a second malignancy was small, so our statistical analyses must be interpreted with caution. Further studies are required to confirm our findings.”5



  1. Dreyer L, Cordtz RL, Hnsen IMJ, et al. Risk of second malignant neoplasm and mortality in patients with rheumatoid arthritis treated with biological DMARDs: a Danish population-based cohort study. Arthritis Rheumatol. 2017; 69 (suppl 10). Abstract# 11L.
  2. Wang D, Li Y, Liu Y, et al. The use of biologic therapies in the treatment of rheumatoid arthritis. Curr Pharm Biotechnol. 2014;15(6):542-8.
  3. Wadström H, Frisell T, Askling J, et al. Malignant Neoplasms in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors, Tocilizumab, Abatacept, or Rituximab in Clinical Practice: A Nationwide Cohort Study From Sweden. JAMA Intern Med. 2017;177(11):1605-1612.
  4. Scott FI, Mamtani R, Brensinger CM, et al. Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer. JAMA Dermatol. 2016;152(2):164-72.
  5. Biologics Do Not Increase the Risk of Second Malignancy in Rheumatoid Arthritis Patients. American College of Rheumatology 2017(Accessed December 26, 2017, at


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