Treatment of rheumatoid arthritis with anti-TNF-alpha agents: A reappraisal

It has been found that tumour necrosis factor(TNF)-alpha plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and the development of drugs targeting this molecule has extended the therapeutical approaches to RA patients. A number of observational studies of large patient series have also been published over the last few years, many of which have been based on national registries designed to monitor the efficacy and safety of anti-TNF agents, and allow healthcare institutions to control expenditure. Registry data can also help in identifying clinical and laboratory findings capable of predicting response. It has been suggested that the percentage of responding patients is lower in everyday clinical practice than that observed in RCTs, possibly because of patient selection, the use of a washout period before inclusion (which may artificially increase disease activity), and differences in doses, co-morbidities and adherence to therapy. A number of safety concerns have been raised since the introduction of anti-TNF agents, and they are now contraindicated in patients with advanced heart failure; however, the most widely debated current issues regard infections and neoplastic diseases. Moreover, the marketing of new and expensive biological agents has made strictly necessary to create systems capable of monitoring their safety and effectiveness in everyday practice, including the use of longitudinal observational studies. As the first published registry of anti-TNFalpha-treated patients in Italy, Lombardy Rheumatology Network (LORHEN) is already making its contribution in this directio

FRI0215 Comparative efficacy and retention rate of tocilizumab and tnf inhibitors used in combination with methotrexate as first-line biologic therapy in rheumatoid arthritis: data from a multicentre observational registry

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Serious infections during anti-TNFalpha treatment in rheumatoid arthritis patients

The objective was to estimate the incidence of serious infections in the patients treated with anti-TNFalpha agents for rheumatoid arthritis (RA) recorded in the Lombardy Rheumatology Network (LORHEN) registry. The study inclusion criteria were met by 1064 of the 1114 patients with long-standing RA, 519 treated with infliximab, 303 with adalimumab, and 242 with etanercept; their mean age was 55.8 years and the mean duration of RA 9.4 years. Seventy-three patients (6.9%) experienced a total of 74 serious infections, an incidence rate for all treatment courses of 35.9 per 1000 patient-years (95% confidence interval [95% CI] 27.66-44.13). Most were lower respiratory tract (34.2%) or skin and soft tissue infections (20.5%). Of the 1064 patients, the 790 treated with anti-TNFalpha after March 2002 underwent screening tests for LTBI; five patients developed active tuberculosis. Three patients died of septic shock. The type of anti-TNFalpha agent did not seem to affect the incidence or site of the infections. Both univariate and multivariate analyses identified age at the start of anti-TNFalpha treatment (p=0.008), baseline erythrocyte sedimentation rate ([ESR] p=0.014), and the concomitant use of corticosteroids (p=0.029) as significant predictors of infections. There was no statistically significant difference in risk between the anti-TNFalpha agent

Predictors of response to anti-TNF therapy in RA patients with moderate or high DAS28 scores.

OBJECTIVES: To identify the clinical factors predicting a good clinical response to anti-TNF therapy in rheumatoid arthritis (RA) patients entered in the LORHEN registry after 5years of treatment with anti-TNF agents and divided into two groups on the basis of their baseline DAS28 scores (moderate>3.2-5.1 [MDA] and high>5.1 [HDA]). METHODS: Disease activity at baseline and after 12months was assessed using the DAS28, and response was evaluated using the EULAR improvement criteria. RESULTS: The study involved 1300 patients with established RA: 975 with HDA and 325 with MDA. After a mean 36-month, 29.6% of the patients had a DAS28 score of less or equal to 2.6 (HDA 25.8% vs. MDA 43.0%; P<0.001) and were considered to be in remission. A higher probability of a good EULAR response in patients with HDA was associated with male gender (F vs. M - OR 0.45, 95% CI 0.26-0.78; P: 0.004), lower age at the start of treatment (OR 0.98, 95% CI 0.96-0.99; P: 0.002), the absence of comorbidities (OR 0.18, 95% CI 0.06-0.52; P: 0.002) or no previous use of corticosteroids (OR 1.92, 95% CI 1.14-3.22; P: 0.015) and the use of adalimumab vs. infliximab (OR 2.21, 95% CI 1.37-3.57; P 0.001); in patients with MDA, the probability of a good EULAR response was associated with male gender (F vs. M - OR 0.39, 95% CI 0.17-0.90; P: 0.027). CONCLUSIONS: With the exception of male gender, the factors predicting a good EULAR response are different in patients with MDA and those with HDA

Incidence of cancer in patients with spondyloarthritis treated with anti-TNF drugs

Objective: To determine the incidence of cancer in TNF inhibitor (TNFi)-treated spondyloarthritis (SpA) patients entered in the GISEA registry, and identify the factors associated with its development. Methods: This observational study involved an open cohort of 3321 SpA patients selected from the GISEA registry, designed to collect real-world clinical data concerning patients with RA or SpA treated with biological drugs. The baseline information includes demographics and clinical parameters. The overall incidence of neoplasias was compared to this observed in the general population according to the Italian Association of Medical Oncology. Results: Of the 3321 SpA patients (1731 males, 52.2%; mean age 47 \ub1 13 years; median disease duration three years, interquartile range [IQR] 0\u20138), 50 developed at least one of 56 malignancies during the follow-up period of up to 12 years of treatment with TNFi. The overall incidence was 6.3/1000 patient-years of follow-up (95% confidence interval [CI] 4.7\u20138.2): 7.3/1000 patient-years (95% CI 4.1\u201311.8) in those treated with ADA; 6.1/1000 patient-years (95% CI 3.8\u20139.4) in those treated with ETN; and 5.8/1000 patient-years (95% CI 3.5\u20139.1) in those treated with INF while in the general population was 5.1/1000 patient-years. Univariate analysis showed that age at the time of starting TNFi (P = 0.001), the presence of comorbidities (P = 0.012), the number of comorbidities (P &lt; 0.001), and HAQ-DI score (P = 0.002) were associated with a higher risk of malignancies. Stepwise regression models showed that only previous neoplasia was a significant predictor of a new malignancy. The type of drug was not associated with the risk of malignancy. Conclusions: The incidence of malignancies among SpA patients treated with the three TNFi was higher than in general population; having had a previous solid cancer is predictive of a new malignancy