Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients.

OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).

Propensity score estimators for the average treatment effect and the average treatment effect on the treated may yield very different estimates.

OBJECTIVE: Propensity score matching is typically used to estimate the average treatment effect for the treated while inverse probability of treatment weighting aims at estimating the population average treatment effect. We illustrate how different estimands can result in very different conclusions. STUDY DESIGN: We applied the two propensity score methods to assess the effect of continuous positive airway pressure on mortality in patients hospitalized for acute heart failure. We used Monte Carlo simulations to investigate the important differences in the two estimates. RESULTS: Continuous positive airway pressure application increased hospital mortality overall, but no continuous positive airway pressure effect was found on the treated. Potential reasons were (1) violation of the positivity assumption; (2) treatment effect was not uniform across the distribution of the propensity score. From simulations, we concluded that positivity bias was of limited magnitude and did not explain the large differences in the point estimates. However, when treatment effect varies according to the propensity score (E[Y(1)-Y(0)|g(X)] is not constant, Y being the outcome and g(X) the propensity score), propensity score matching ATT estimate could strongly differ from the inverse probability of treatment weighting-average treatment effect estimate. We show that this empirical result is supported by theory. CONCLUSION: Although both approaches are recommended as valid methods for causal inference, propensity score-matching for ATT and inverse probability of treatment weighting for average treatment effect yield substantially different estimates of treatment effect. The choice of the estimand should drive the choice of the method.

Hepatitis C virus-associated polyarteritis nodosa.

OBJECTIVE: To analyze the main characteristics and outcome of polyarteritis nodosa (PAN)-type vasculitis associated with hepatitis C virus (HCV). METHODS: We reported the characteristics and outcome of 31 patients chronically infected with HCV who satisfied the American College of Rheumatology and Chapel Hill criteria for PAN, seen between 1990 and 2009 in a university center. RESULTS: Among a cohort of 161 patients with HCV-related vasculitis, 31 (19.3%) were diagnosed as having PAN. The median age was 64.5 years (interquartile range 49.5-70.5 years), with 54.8% women. Compared with HCV-associated mixed cryoglobulinemia (HCV-MC) vasculitis, HCV-PAN displayed a more severe and acute clinical presentation with more frequent fever and weight loss (P < 0.0001), severe hypertension (P = 0.0006), gastrointestinal tract involvement (P < 0.0001), severe acute sensory-motor multifocal mononeuropathy (P < 0.0001), kidney and liver microaneurysms (P = 0.002), and increased C-reactive protein level (P < 0.0001). Complete clinical remission of vasculitis was achieved in 79.3% of HCV-PAN patients compared to 57.5% of HCV-MC patients (P = 0.05). In multivariate analysis, skin involvement (odds ratio [OR] 2.81, 95% confidence interval [95% CI] 1.27-6.33) and PAN-type vasculitis (OR 3.01, 95% CI 1.16-8.96) were independently associated with a complete clinical response of HCV vasculitis. A glomerular filtration rate <70 ml/minute (OR 0.54, 95% CI 0.24-1.21) was negatively associated with a complete clinical response of HCV vasculitis. The 5-year survival rate was 86% in the entire cohort, regardless of the vasculitis type. CONCLUSION: HCV-PAN accounts for 19.3% of our cohort of HCV vasculitis. HCV-PAN displays a more severe and acute clinical presentation and a higher rate of clinical remission.