RESUMO
OBJECTIVES: To compare retention rates of adalimumab, etanercept and infliximab as first-line biotherapy in rheumatoid arthritis (RA), to determine causes of discontinuation, retention-associated factors, and retention rates of possible second-line TNF-α inhibitors (TNFi). METHODS: In this retrolective, multicentric study, medical charts of RA patients starting TNFi between March 2005 and April 2009 were reviewed, with follow-up between two and six years. The retention rate was estimated using the Kaplan-Meier method. Comparison between TNFi was done after adjustment using a Cox model. Factors associated with better retention were identified by multivariate analysis. RESULTS: Of the 706 patients included, the percentage continuing treatment after two years was 54.9, 61.9 and 48.7%, and the median retention was 31, 45 and 23 months for adalimumab, etanercept and infliximab, respectively. The hazard ratios (HRs) for discontinuation were greater with adalimumab and infliximab than etanercept (1.315, 95% CI [1.050-1.648] and 1.380, 95% CI [1.041-1.828], respectively). The HR for discontinuation due to inefficacy was significantly higher with adalimumab than etanercept. Adverse events were significantly higher with infliximab than etanercept. Past use of more DMARDs and higher baseline ESR were associated with better retention. The median retention of the second-line TNFi was 11, 43 and 19.1 months for adalimumab, etanercept, and infliximab, respectively. HRs for adalimumab discontinuation due to all causes were significantly greater than for etanercept. CONCLUSIONS: Etanercept had a better retention rate than adalimumab and infliximab as first-line biotherapy in RA, and than adalimumab as second-line biotherapy.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab , Adulto , Antirreumáticos/uso terapêutico , Etanercepte , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Synovial hyperplasia in rheumatoid arthritis (RA) has been associated with apoptosis deficiency of RA fibroblast-like synoviocytes (FLSs). Celecoxib is a non-steroidal anti-inflammatory drug that has been demonstrated to induce apoptosis in some cellular systems. We have therefore examined the dose- and time-dependent effects of celecoxib on RA FLS viability. Treatment of RA FLSs with celecoxib for 24 hours reduced their viability in a dose-dependent manner. Analysis of celecoxib-treated RA FLSs for their content of apoptotic and necrotic cells by Annexin V staining and TO-PRO-3 uptake displayed only few apoptotic cells. Caspase 3, a key mediator of apoptosis, was not activated in celecoxib-treated RA FLSs, and the presence of specific caspase 3 or pan-caspase inhibitors did not affect celecoxib-induced cell death. Moreover, we could not detect other signs of apoptosis, such as cleavage of poly(ADP-ribose) polymerase, caspase 8 or 9, or DNA fragmentation. We therefore conclude that apoptosis is not the major death pathway in celecoxib-treated RA FLSs.