Cancer Risk in Patients With Rheumatoid Arthritis Treated With Anti-Tumor Necrosis Factor alpha Therapies Does the Risk Change With the Time Since Start of Treatment?

Department of Medicine Solna, Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
Arthritis & Rheumatology (Impact Factor: 7.76). 11/2009; 60(11):3180-9. DOI: 10.1002/art.24941
Source: PubMed


To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.
By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.
During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.
During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.

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Available from: Johan Askling, Mar 29, 2014
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    • "Use of disease-modifying treatment that controls chronic inflammation may reduce the elevated risk associated with uncontrolled RA. Recent long-term studies have failed to identify an effect of TNF antagonists on the incidence of cancer, including lymphoma (with exception of NMSC), and also determined that the relative risk of cancer did not increase with time since first starting a TNF antagonist or with cumulative duration of TNF antagonist therapy [31-33]. Lastly, mortality rates were lower in patients receiving ADA therapy in ReAct and ReAlise than observed in a matched population without RA, and there was no increase in the overall mortality rate over the course of the studies. "
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    • "An integrated analysis of three patient databases found that the risk of malignancy in RA patients treated with anti-TNF biologics does not increase with time [130]. "
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    • "Interestingly, anti-inflammatory steroid treatment in RA reduces the risk of developing lymphoma (Hellgren et al. 2010). It has been postulated that it is the severity of inflammation and duration of the rheumatoid arthritis that contributes to the increased risk of lymphoma (Askling et al. 2009). The risk of hematological cancer is higher in younger RA patients (Chen et al. 2011). "
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