A Randomized, Double‐Blind Study Comparing Pharmacokinetics and Pharmacodynamics of Proposed Biosimilar ABP 798 With Rituximab Reference Product in Subjects With Moderate to Severe Rheumatoid Arthritis

ABP 798 is a proposed biosimilar to rituximab reference product (RP), an anti-CD20 monoclonal antibody. Pharmacokinetics (PK), pharmacodynamics (PD), and safety results from the comparative clinical study that evaluated the PK, PD, safety, efficacy, and immunogenicity of ABP 798 versus rituximab RP are presented here. Subjects with moderate to severe rheumatoid arthritis (RA) received 2 doses of ABP 798, United States-sourced RP (rituximab US) or European Union-sourced RP (rituximab EU), each consisting of two 1000-mg infusions 2 weeks apart. For the second dose (week 24), ABP 798- and rituximab EU-treated subjects received the same treatment; rituximab US-treated subjects transitioned to ABP 798. End points included area under the serum concentration-time curve from time 0 extrapolated to infinity and maximum observed serum concentration following the second infusion of the first dose (PK) and percentage of subjects with complete CD19+ cell depletion days 1-33 (PD). Primary analysis established PK similarity between ABP 798 and rituximab RP based on 90% confidence intervals of the adjusted geometric mean ratios being within a prespecified equivalence margin of 0.8 and 1.25. Complete CD19+ B-cell depletion on day 3 among groups confirmed PD similarity. These findings demonstrated PK/PD similarity between ABP 798 and rituximab RP in subjects with moderate to severe RA

Medico-economic evaluation of infliximab in rheumatoid arthritis—prospective French study of a cohort of 635 patients monitored for two years

Objectives. To perform, in real conditions of prescription, the medico-economic evaluation of infliximab in severe RA. Methods. A cost-effectiveness analysis of the annual costs was done with a comparison between the previous and the following year under infliximab. The effectiveness, determined from the HAQ, was expressed in clinically significant units and in quality-adjusted life years (QALYs). The incremental net benefit (INB), defined as willingness to pay (λ), was used to express the results. Results. A cohort of 635 patients was formed. Before the use of infliximab, after 1 and 2 years, the mean annual cost per patient for the care of RA was €9832, 27 723 and 46 704, respectively. Among the direct costs, infliximab accounts for €21 182 for the first year. The distribution of the different costs was similar after 2 years. By using the INB, the difference before and after 1 year under infliximab is significant, on average by 1.86 (s.e.m. = 0.76) when the effectiveness is expressed in clinically significant units. For severe HAQ, λ is €9841 (18 593 for all HAQ). When it is expressed in QALYs, also for severe HAQ, λ >€100 000. This can be explained by a short follow-up although severe complication of RA appears later. Conclusion. An evaluation of the more long-term costs is required in order to determine whether there are any full economic benefits with this treatmen

Approximation of the second fundamental form of a hypersurface of a Riemannian manifold

We give a general Riemannian framework to the study of approximation of curvature measures, using the theory of the normal cycle. Moreover, we introduce a differential form which allows to define a new type of curvature measure encoding the second fundamental form of a hypersurface, and to extend this notion to geometric compact subsets of a Riemannian manifold . Finally, if a geometric compact subset is close to a smooth hypersurface of a Riemannian manifold, we compare their second fundamental form (in the previous sense), and give a bound of their difference in terms of geometric invariants and the mass of the involved normal cycles

Approximation of Normal Cycles

This report deals with approximations of geometric data defined on a hypersurf- ace of the Euclidean space E^n. Using geometric measure theory, we evaluate an upper bound on the flat norm of the difference of the normal cycle of a compact subset of E^n whose boundary is a smooth (closed oriented embedded) hypersurface, and the normal cycle of a compact geometric subset of E^n "close to it". We deduce bounds between the difference of the curvature measures of the smooth hypersurface and the curvature measures of the geometric compact subset

Approximation of the Curvature Measures of a Smooth Surface endowed with a Mesh

This report deals with the approximation of a smooth surface M by a triangulated mesh T. We give an explicit bound on the difference of the curvature measures of M and the curvature measures of T, when T is close to M. The result is obtained by applying the theory of the normal cycle