Anti-TNF Therapy Is Not Associated with an Increase in Neoplasias in Patients with Spondyloarthritis (SpA): Results from the GISEA Registry

Background/Purpose: The use of TNF inhibitors (TNFIs) has led to efficient control of the signs and symptoms of SpA and rheumatoid arthritis (RA), and significantly improved the patients’ quality of life. However, as most patients need often indeterminately long-term treatment (especially those with SpA), rheumatologists must be aware of treatment side effects such as malignances, even though nine clinical trials of etanercept in SpA patients did not find an increased risk. The aim of this study was to evaluate the risk of malignances in the TNFI-treated SpA patients in the Gruppo Italiano Studio Early Arthritis( GISEA) Registry, and assess predictors of malignancies Methods: The Registry, which is designed to collect real-world clinical data concerning RA and SpA patients receiving biological drugs as part of routine care, was approved by local Ethics Committees, and enrols patients aged ≥18 years who have given their written informed consent. The baseline information includes demographics, disease duration, HAQ, DAS-28, BASDAI, BASFI and BASMI scores, steroid use (defined as actively receiving oral steroids at the time of recruitment), smoking history and comorbidities. Results: The analysis involved 3321 SpA patients (1731 males, 52.2%; mean age 47±13 years; median disease duration three years, interquartile range [IQR] 0, 8 years): 1065 (32%) treated with infliximab (IFN), 1052 (32%) with adalimumab (ADA), and 1204 (36%) with etanercept (ETN). Two thousand, one hundred and five (63.4%) had a median of one comorbity (IQR 0, 2], the most frequent being hypertension (701), thyroid diseases (281), diabetes mellitus (207), cardiopathy (189), and osteoporosis (145). In combination with the biological drug, 919 patients (27.7%) received steroids and 2451 (79.9%) at least one DMARD. The median follow-up time was three months (IQR 12 years). During 12 years of TNFI treatment, 50 patients experienced at least one of 56 neoplasias, 28% of which occurred during the first 12 months. Overall incidence was 6.3/1000 patient-years of follow-up (95% CI 4.7–8.2): 7.3/1000 (95% CI 4.1–11.8) among those treated with ADA; 6.1/1000 (95% CI 3.8–9.4) among those treated with ETN; and 5.8/1000 (95% CI 3.5–9.1) among those treated with IFN. Univariate analysis showed that age at the start of anti-TNF treatment (p=0.001), the number of comorbidities (p<0.001), and HAQ score (p=0.002) were associated with a high risk of malignancy. Multivariate models showed that male gender (hazard ratio [HR] 4.5, 95%CI1.3-16.0; p=0.020), age at the start of anti-TNF treatment (HR 1.1, 95%CI 1.01-1.11; p=0.020), and HAQ score (HR 2.8, 95%CI1.5-5.3; p=0.002) were statistically significant predictors of malignances. Ten of the 50 patients experiencing a neoplasia had had a previous solid cancer (HR 11.2, 95%CI 4.4-28.4; p