Among patients with immune-mediated diseases and a history of malignancy, cancer recurrence rates were similar regardless of whether they received tumor necrosis factor inhibitors, traditional immunosuppressants, or no immunosuppression, according to a meta-analysis of 16 cohort and case-control studies.
“However, there is a need for larger studies to prospectively monitor for cancer recurrence and new malignancies in this population to better inform our practice,” wrote Dr. Edward Shelton of Massachusetts General Hospital in Boston, and his associates. The report is in the July issue of Gastroenterology.
Patients with immune-mediated diseases often have a history of malignancy, raising questions about the effects of therapies that target the immune system, the researchers noted. However, relevant studies have been “small with few events, preventing robust estimates of risk,” they said. They searched Medline, Embase, and conference proceedings through April 2015 for studies of the risk of primary or recurrent cancer among patients with a history of malignancy who were exposed to thiopurines, methotrexate, or anti-TNF agents, or no immunosuppression. Among the 16 studies meeting these criteria, seven included patients with rheumatoid arthritis, seven included patients with inflammatory bowel disease, one included both diseases, and one included patients with psoriasis. Twelve were cohort studies, one was a case-control study, and three were case series. The resulting meta-analysis comprised 11,702 patients who contributed a total of 31,258 person-years of follow-up (Gastroenterology 2016 May 13. doi: 10.1053/j.gastro.2016.03.037).
Rates of cancer recurrence were statistically similar among patients who received no immunosuppression, anti-TNF therapy, traditional immune modulators, or combination regimens (P greater than .1 for differences among groups). Numerically, however, the risk of recurrent cancer was highest with combination immunotherapy (54.5 cases per 1,000 person-years of follow-up), compared with 37.5 cases per 1,000 person-years for patients who did not receive immunosuppressive treatment, 36.2 cases per 1,000 person-years for patients who received traditional immunomodulator monotherapy, and 33.8 cases per 1,000 person-years for patients who received anti-TNF agents. Analyses of subgroups of patients with new or recurrent cancers, or various types of therapies, and of specific immune-mediated diseases yielded “similar results, with no increase in risk,” said the researchers. Furthermore, rates of cancer recurrence did not statistically differ depending on whether patients started immunosuppression less than or more than 6 years after their index cancer (P = .43).
“Treatment decisions after a cancer diagnosis are complex, and must take into account the natural history of cancer, histologic type and stage, time from diagnosis, and course of underlying chronic inflammatory disease,” the researchers noted. “Our findings suggest that anti-TNF therapy, conventional immunosuppressant therapy, or combination immunosuppression are not associated with an increased risk of cancer recurrence in this population.”
The researchers cited several limitations. Notably, three of the studies included only 20 patients, and the studies included variable index cancers and methods for detecting recurrent cancers. “It also is possible, and likely, that patients who were at high risk for recurrence were not recommenced on immunosuppression, and consequently our findings may be more applicable to a population in which the patient and physicians were comfortable with re-initiation of therapy,” they said.
The National Institutes of Health supported several of the study investigators. Dr. Shelton had no disclosures. Five coinvestigators disclosed relationships with a number of pharmaceutical companies.