The Risk of Cancer with Tumor Necrosis Factor Inhibitors in Patients Concomitantly Exposed to Non-Biological Immunosuppressants Differs According to the Indication

Layla Saliba¹, Guillaume Moulis², Malak Aboutaam³, Grégory Pugnet², Vanessa Rousseau¹, Leila Chebane¹, Nadine Petitpain⁴, Bernadette Baldin⁵, Jean-Louis Montastruc¹ and Haleh Bagheri¹, ¹Toulouse University Hospital, Clinical Pharmacology Department, University of Toulouse, Toulouse, France, ²Toulouse University Hospital, Department of Internal Medicine, University of Toulouse, INSERM UMR 1027, Toulouse, France, ³Reims University Hospital, Pharmacovigilance Regional Center, Reims, France, ⁴Nancy University Hospital, Pharmacovigilance Regional Center, Nancy, France, ⁵Nice University Hospital, Pharmacovigilance Regional Center, Nice, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: anti-TNF therapy, autoimmune diseases, cancer and rheumatoid arthritis (RA), DMARDs

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy I: Safety of Biologics and Small Molecules in Rheumatoid Arthritis - Malignancy and Infection

Session Type: Abstract Submissions (ACR)

Background/Purpose: The risk of cancer with TNF-a inhibitor (TNFi) in patients concomitantly exposed to non-biological immunosuppressants (NBIS) is highly debated in RA, AS and psoriasis/PsA. In contrast, it has been suggested that the excess risk of some lymphomas in IBD was due to NBIS exposure and not to add-on TNFi. The primary objective of this study was to detect a signal of an increased risk of cancer in patients treated with TNFi and NBIS compared with NBIS alone for these diseases. The secondary objective was to compare this risk between the different TNFi.

Methods: We conducted a disproportionality analysis (case/non-case study) in the French National PharmacoVigilance Database. Study population was all the reports of serious adverse drug reactions from 2000 to 2010 in patients treated with NBIS for labeled indications of TNFi. Cases were all the reports of cancer that occurred after a minimal exposure of three months to NBIS. Non-cases were all the other reports. We searched for exposure to TNFi in cases and non-cases, leading to Reporting Odds Ratio (ROR) calculations. The analyses were stratified on the condition and the type of cancer (blood and solid cancer, non-melanoma skin cancers – NMSCs, melanoma), and were adjusted on the age, the gender, the history of cancer, the type of NBIS and the year of reporting. Sensitivity analyses were carried out to detect event- or drug-related competition biases.

Results: Out of the 1,918 reports meeting the study population definition, 217 were cases (135 solid and 82 blood cancers). RA was the leading indication among the study population (n=1200), followed by IBD (n=422), psoriasis or PsA (n=126), and AS (n=92). Exposure to TNFi was found in 156 (72.7%) cases (infliximab, 48.9%, adalimumab, 28.8% and etanercept, 37.2%) and in 698 (43.0%) non-cases (infliximab, 63.5%, adalimumab, 18.8% and etanercept, 18.8%). A safety signal was found as regards the risk of cancer with exposure to both TNFi and NBIS compared with NBIS alone in RA (ROR: 5.43, 95%CI[3.52-8.38]). The signal was significant for every type of cancer, but was the most important for NMSCs (ROR: 20.17, 95%CI[2.49-163.36]). In contrast, no signal was found in AS, psoriasis/PsA and IBD, whatever the type of cancer. As regards the secondary objective, there was no difference between TNFis. Sensitivity analyses confirmed these results.

Conclusion: This study adds strong argument for an increased risk of cancer, and particularly NMSCs, in RA patients exposed to TNFi in addition to NBIS compared with NBIS alone. The signal seems similar with infliximab, adalimumab and etanercept. In contrast, it suggests that there is no signal in AS, psoriasis/PsA and IBD.

Disclosure:

L. Saliba,
None;

G. Moulis,
None;

M. Aboutaam,
None;

G. Pugnet,
None;

V. Rousseau,
None;

L. Chebane,
None;

N. Petitpain,
None;

B. Baldin,
None;

J. L. Montastruc,
None;

H. Bagheri,
None.

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