Search

Summary Our objective was to evaluate the contribution of monitoring B cell subset depletion after rituximab in patients with rheumatoid arthritis (RA) in order to guide reintroduction to forestall relapse. This prospective, monocentre study included all RA patients receiving two 1-g rituximab infusions at a 15-day interval. The patients were followed clinically and biologically every 2 months until rituximab reintroduction. The physician was blinded to lymphocyte-typing results to diagnose relapse and, hence, retreatment. Among the 39 patients included between March 2010 and December 2011 and followed until April 2013, seven received two rituximab cycles, yielding a total of 46 cycles for analysis. After the two rituximab cycles, the total number of CD19+ B cells decreased significantly (0·155 versus 0·0002 G/l, P < 0·0001), with complete depletions in all patients of CD19+ CD38++ CD24++ (transitional) (P < 0·0001) and CD19+ CD27+ (memory) B lymphocytes. A significant majority of patients relapsed within the 4 months following repopulation of total B (P = 0·036), B transitional (P = 0·007) and B memory (P = 0·01) lymphocytes. CD19+ B lymphocyte repopulation preceded clinical RA relapse and enabled its prediction 4 months in advance. Hence, monitoring of CD19+ B lymphocytes could serve as a tool to predict those relapses.

Objective The aim of this study was to assess intraobserver and interobserver reliability of minor salivary gland biopsy (MSGB) in SS. Methods All MSGBs available from the Tolerance and Efficacy of Rituximab in Primary Sjogren's Syndrome (TEARS) study were subjected to a standardized blinded assessment by a single specifically trained pathologist twice at a 2 month interval; both the Chisholm-Mason (CM) grade and the focus score (FS) were determined. Baseline histopathological reports by local pathologists at each study centre were compared with the first standardized blinded assessment. Agreement was assessed for the dichotomized FS (dFS) and dichotomized CM (dCM) grade, as well as for nine other histopathological features. Results Eighty-nine MSGBs were studied. Intraobserver κ values were 1 for dFS, 0.80 for dCM, 0.67 for germinal centre-like structures, 0.44 for fibrosis and 0.29 for confluent foci. Most of the local histopathological reports based their diagnosis on the CM grade, although the FS was often reported or the data needed to determine it were provided. Interobserver agreement κ values were 0.71 for dFS, 0.64 for dCM, 0.46 for focal lymphocytic sialadenitis, 0.42 for non-specific chronic inflammation and 0.16 for fibrosis. Conclusion Although FS reliability was good, disparities were noted in the assessment methods used by local pathologists. The protocol for FS determination was not followed routinely, with the result that the FS was often overestimated. Germinal centre-like structures, which predict lymphoma, showed good reliability but were inconsistently reported.

Objectives. Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF drugs. This retrospective study aimed to describe the different PAEs that have occurred in a population of SpA patients treated with anti-TNF drugs, and to determine whether they are drug specific. Methods. Since 2000, we have followed 296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis, 12 Crohn’s disease) and 77 psoriatic arthritis] treated with at least one anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated only with conventional DMARDs who served as controls. Considering the cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in exposed patients were calculated. Results. Respective cumulative exposure times were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We observed the following PAEs: five psoriasis (three under infliximab and one with etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept) and four IBD (three under etanercept and one under infliximab). There was no significant association among any of these PAEs and a specific anti-TNF agent; nor significant difference in the overall PAEs among patients receiving anti-TNF drugs or controls (P ¼ 0.303), the latter experiencing two psoriasis and three AAU. Conclusions. Undesirable side effects—IBD, AAU and psoriasis—may appear with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence supports any PAEs to be anti-TNF agent-specific in SpA.