Malignancies 32% More Likely in RA

Patients with rheumatoid arthritis run an increased risk of malignant cancers, independent of biologic and disease-modifying anti-rheumatic drugs (DMARDS), researchers say.

In a study comparing matched cohorts of people with and without rheumatoid arthritis, those with rheumatoid arthritis were 32 percent more likely to have malignancies.

“Cancer surveillance is imperative in all patients with RA,” writes Shafay Raheel, M.D., of the Mayo Clinic College of Medicine in Minnesota, and colleagues, in the International Journal of Rheumatology.

Previous research has already established an increased risk of malignancies in patients with rheumatic diseases, including rheumatoid arthritis. And, it has pinned this increased risk to the pathobiology of rheumatic diseases including inflammatory burden, immunological defects and personal and environmental risk factors such as smoking.

But the research has not fully explored these phenomena in a non-referral community-based population, the researchers write.

Dr. Raheel and colleagues analyzed data from the Rochester Epidemiology Project, which allows researchers access to medical records from all Minnesota and Wisconsin medical providers.

Researchers looked at a cohort of cases of rheumatoid arthritis diagnosed between January 1, 1980 and December 31, 2007 among Olmsted County, Minnesota residents over age 18.

They matched these patients to a cohort of Olmsted County Minnesota residents without rheumatoid arthritis of similar age, sex and years. They retrieved non-melanoma skin cancer diagnoses from the Mayo Clinic Cancer Registry.

The researchers identified 813 incident cases of rheumatoid arthritis, with a mean age of diagnosis of 55.9 years. They defined an index date for the matching person without rheumatoid arthritis as the date the corresponding person was diagnosed. The mean length of follow-up was 14.1 years for the people with rheumatoid arthritis and 14.9 years for the people without that diagnosis.

Prior to the diagnosis or index dates, 52 patients with rheumatoid arthritis and 66 without rheumatoid arthritis had malignancies, excluding non-melanoma skin cancer. The difference was not statistically significant (P = 0.21). But including non-melanoma skin cancer, there were 79 patients in the rheumatoid arthritis (RA) cohort and 108 in the non-RA cohort, and this difference was statistically significant (P = 0.024).

Excluding non-melanoma skin cancer, 148 patients with RA developed malignancies (11.8%) during the follow-up period, compared to 118 people without RA (9.3%), for a hazard ratio (HR) of 1.32 (95% confidence interval (CI): 1.03- 1.68).

Including non-melanoma skin cancer, 194 people in the RA cohort had malignancies, compared with 179 among the people without RA.

People with rheumatoid arthritis had a much higher incidence of hematologic cancers (HR 3.58; 95% CI 1.69-7.60), and lung cancer (HR 1.97; 95% CI: 1.08-3.59).

The researchers also found a positive correlation between smoking and malignancies, and between erosions or destructive joint changes and smoking.

They also found that patients with rheumatoid arthritis who used glucocorticoids were more likely to have malignancies (HR 1.57; 95% CI: 1.04-2.39), and the association persisted after adjustments for erythrocyte sedimentation rate at rheumatoid arthritis diagnosis, rheumatoid factor positivity and current smoking.

However, the researchers speculated that glucocorticoids use might be confounded with more severe disease.

Methotrexate use was not associated with an increased malignancy risk, nor was the use of other DMARDS or biologics.

Hematologic cancers appeared to drive the increased risk of cancer, and the researchers noted “a considerable body of evidence” establishing rheumatoid arthritis and RA disease activity as pathogenic factors in the development of lymphoma.

Previous studies have shown an increased risk of both squamous cell and basal cell cancer in patients with RA who had not had biologic drugs and in patients who were starting tumor necrosis factor (TNF) inhibitor treatment. One study in Sweden demonstrated a 20% increase in the risk of basal cell carcinoma and nearly a double risk of squamous cell cancer in patients with rheumatoid arthritis.

One study conducted among 13,001 patients using the U.S. National Cancer Institute Surveillance Epidemiology and End Results database showed an increased risk for skin cancers, but not tumors or lymphoproliferative malignancies, with biologic therapy.

Dr. Raheel and colleagues identified their own study’s population-based design and its complete medical record review as strengths. They were able to include both patients with RA and people from the same community who matched them in age and sex, reducing the risk of bias in referral populations.

The limitations may include the fact that the population of Olmsted County is predominantly Caucasian, wrote researchers who acknowledged that their study didn’t have enough statistical power to detect increased risks for cancer subtypes.

Still, the data was strong enough for them to unequivocally conclude that “there was a small to moderately increased risk of malignancies excluding [non-melanoma skin cancers] in RA patients.”

References:

Shafay Raheel, Cynthia S. Crowson, et al. “Risk of Malignant Neoplasm in Patients with Incident Rheumatoid Arthritis 1980–2007 in relation to a Comparator Cohort: A Population-Based Study,” International Journal of Rheumatology. http://dx.doi.org/10.1155/2016/4609486

Pauline Raaschou, Julia F Simard, et al. “Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden,” The British Medical Journal. Jan. 28, 2016.  DOI: http://dx.doi.org/10.1136/bmj.i262  Cite this as: BMJ 2016;352:i262

Wassila Amari, Angelique L. Zeringue, et al. “Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis," Rheumatology. March 16, 2011. DOI: 10.1093/rheumatology/ker113