P335 Cancer recurrence with immunosuppressive therapy in immune-mediated diseases: a systematic review and meta-analysis
E. Shelton*1, D. Laharie2, F. Scott3, R. Mamtani4, J. Lewis4, J.-F. Colombel5, A. Ananthakrishnan1
1Massachusetts General Hospital, Boston, Massachusetts, United States, 2University-Bordeaux, Bordeaux, France, 3University of Pennsylvania, Philadelphia, Pennsylvania, United States, 4University of Pennsylvania Perelman School of Medicine, Division of Gastroenterology, Philadelphia, Pennsylvania, United States, 5Mount Sinai, Icahn School of Medicine, New York, New York, United States
Physicians frequently encounter patients with immune-mediated diseases and a history of malignancy. There are limited data on the safety of immunosuppressive therapy in this setting. Published studies have been small, with few events, precluding robust estimates of risk.
We searched Medline, EMBASE, and conference proceedings for terms related to immune-mediated disease, immunosuppressive therapy, and cancer recurrence from inception to April 2015. We included 16 studies (rheumatoid arthritis [RA]-8, inflammatory bowel disease [IBD]-8, psoriasis-1) and stratified studies by immunosuppressive exposure (anti-TNF, conventional immunomodulator [IMM], or no immunosuppression [no IS)]). A random-effects meta-analysis was performed to calculate pooled incidence rates, as well as risk differences between the various treatments.
Our analysis included 11 702 persons contributing 31 258 person-years (p-yr) of follow-up after prior cancer diagnosis. There were 1 698 instances of a new primary or recurrent cancer.
Rates of cancer recurrence were similar across patient groups: anti-TNF therapy 33.8/1 000 p-yr, immunomodulator therapy 36.2/1 000 p-yr, and no immunosuppression 37.5/1 000 p-yr, and was numerically higher for combination immunosuppression (54.5/1 000 p-yr) (p > 0.1 for all). The pooled incidence rates of new cancers were not statistically different between the no IS (24.9/1 000 p-yr; 95% CI 5.6–44.3), anti-TNF (28.8/1 000 p-yr; 95% CI 7.6–50.0), and IMM (38.4/1 000 p-yr; 95% CI 12.2–64.6) groups, respectively though the latter had numerically the highest rates. We also observed similar rates of new or recurrent cancer with thiopurines (37.9 per 1 000 p-yr, 95% CI 5.9–69.9) compared with methotrexate (38.9, 95% CI 14.7–63.0) (p = 0.78). Amongst the 2 studies that included index skin cancer alone, the risk of new or recurrent cancers was statistically significantly greater with IMM (71.6 per 1 000 p-yr, 95% CI 58.9–84.2) when compared with no IS (50.8 per 1 000 p-yr, 95% CI 43.7–57.8) and numerically (but not statistically) higher with anti-TNF therapy (55.5 per 1,000 p-y, 95% CI 44.7–66.3). In contrast, excluding studies with skin cancer as the index malignancy yielded similar rates of new or recurrent cancer with IMM (26.3 per 1 000 p-yr), anti-TNF (24.3 per 1 000 p-yr) or no IS (31.2 per 1 000 p-yr).
Figure 1. Forest plot of risk of recurrence of cancer or development of new primary by type of immunosuppression in individuals with a prior history of cancer.
Similar rates of cancer recurrence in individuals with prior cancer were observed with no immunosuppression, anti-TNF, immunomodulator, or combination therapy in this meta-analysis.