Assessment timing and choice of outcome measure in determining treatment response in chronic inflammatory demyelinating polyneuropathy: a post-hoc analysis of the PRISM trial

Introduction/Aims: Treatment response and its timing are variable in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we assessed the variability using multiple outcome measures. Methods: We performed a post hoc analysis of the PRISM trial, a 24-week prospective, multicenter, single-arm, open-label, phase III study of a 10% intravenous immunoglobulin preparation for CIDP. We ascertained timing of response with primary/secondary outcome measures. Results: At 6 weeks after treatment initiation, 13 of 40 subjects (32.5%) were defined as responders on the primary outcome measure, the adjusted Inflammatory Neuropathy Cause And Treatment (INCAT) scale. This increased to 20 of 41 (48.8%) at 12 weeks and to 32 of 42 (76.2%) at 24 weeks. Use of minimal important difference (MID)-determined amelioration of the inflammatory Rasch-built Overall Disability Scale (I-RODS), or of the Medical Research Council sum score (MRCSS), or of dominant hand-grip strength, in addition to the adjusted INCAT, indicated a sensitivity of 41.7% in identifying adjusted INCAT nonresponders at week 12 who subsequently responded at week 24. Specificity was 60% vs INCAT nonresponders at week 24. Consideration of amelioration of any amplitude on any secondary outcome measure indicated a 75% sensitivity, but only 30% specificity vs adjusted INCAT nonresponders at week 24. Discussion: Immunoglobulin treatment continuation may be justified for up to 24 weeks in CIDP. Additional outcome measures may help in the early treatment stages to predict delayed response on the adjusted INCAT. However, their use is limited by high false-positive rates. More robust, reliable, and relevant outcome measures are needed to detect early improvement in immunoglobulin-treated CIDP

An international multicenter efficacy and safety study of IqYmune in initial and maintenance treatment of patients with chronic inflammatory demyelinating polyradiculoneuropathy: PRISM study

This prospective, multicenter, single-arm, open-label phase 3 study aimed to evaluate the efficacy and safety of IqYmune in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients received one induction dose of 2 g/kg and then seven maintenance doses of 1 g/kg at 3-week intervals. The primary endpoint was the responder rate at the end of study (EOS), defined as an improvement of 651 point on the adjusted inflammatory neuropathy cause and treatment (INCAT) disability scale. The responder rate was compared with the responder rate of a historical placebo group (33.3%). Secondary endpoints included changes from baseline to EOS of adjusted INCAT disability score, grip strength, Medical Research Council (MRC) sum score, Rasch-modified MRC sum score, Rasch-built overall disability scale score and the clinical global impression. Forty-two patients, including 23 Ig-na\uefve and 19 Ig-pre-treated, were included in the efficacy set. The overall response rate at EOS was 76.2% (95% confidence interval [60.5%-87.9%]). The superiority of IqYmune compared to the historical placebo control was demonstrated (P < .0001). The responder rate was numerically higher in Ig-pre-treated than in Ig-na\uefve patients but confidence intervals were overlapping (84.2% [60.4%-96.6%] vs 69.6% [47.1%-86.8%]). All secondary endpoints confirmed this conclusion. The median time to response was 15 weeks [8.9-19.1 weeks]. A total of 156 adverse events including five serious were considered related to IqYmune, 87.2% were mild. Neither hemolysis nor signs of renal or hepatic impairment were observed. These results demonstrate that IqYmune is an effective and well-tolerated treatment in patients with CIDP

The Cenomanian-Turonian boundary on the Saharan Platform (Tunisia and Algeria)

International audienceSeveral transects made of correlated stratigraphic sections and well logs have been constructed spanning southern Tunisia and the Algerian Sahara (Tinrhert) for comparison with earlier results obtained in the Saharan Atlas. The study is based on fades analysis, sedimentology, biostratigraphy focused on ammonites and foraminifers) as well as whole rock geochemistry (delta C-13). These suggest that the entire northern Sahara Platform underwent marine flooding that commenced just prior to the onset of the global positive delta C-13 shift documented for the Cenomanian-Turonian boundary. This flooding occurred in two phases. The first phase is expressed by the deposition of deeper-water, light-coloured bioturbated mudstones overlying the shallow-water deposits comprising the local Cenomanian successions. But in some places in the Central Sahara (Hassi Messaoud area, Tihemboka Arch) as well as in the Saharan Atlas, shallow-water carbonates kept up locally with the relative sea-level rise to build up isolated carbonate platforms. The topographic lows or saddles between these areas could have been formed through differential accumulation rates. During the second phase, flooding resumed and black shales were deposited over the mudstones in the saddles. The occurrence of black shales in these saddles is limited to the northern edge of the platform (Saharan Atlas of Algeria, Gafsa Trough in southern Tunisia). On the platform, this phase is represented by the same kind of mudstones deposited during the first phase of the flooding (southern Tunisia), or by ammonite-rich chalks in the intra-cratonic basin of the Tinrhert (southern Algeria). Black-shale deposition ceased in the early Turonian. Based on the delta C-13 curve, the latest Cenomanian flooding of the Sahara Platform is roughly coeval with that documented for the US Western Interior. During the first phase of the transgression, that is before the occurrence of the large Whiteinella of the W. archeocretacea Zone in the black shale unit, planktic foraminifers are dominated by small globulose forms of the Hedbergella delrioensis type, associated with Heterohelicidae. Keeled forms (rotaliporids, dicarinellids) are scarce and always very small when present. Perhaps these dwarfed forms were adapted to the restricted environments of the extensive intracratonic seaways crossing the Saharan Platform to the Benoue Trough in Nigeria

FIRST ARCHAEOLOGICAL INVESTIGATIONS IN THE CHOTT EL JERID AREA, SOUTHERN TUNISIA

Questo lavoro presenta i risultati preliminari delle ricerche archeologiche nel sud tunisino. Il programma triennale, sebbene fortemente ostacolato dalla grave situazione interna e drammaticamente scosso dagli attentati del 2015, ha comunque permesso una prima valutazione del potenziale archeologico della regione del Chott el Jerid, nel governatorato di Kebili. Le ricognizioni geoarcheologiche e i primi interventi di scavo, unitamente a un’articolata serie di campionamenti per la ricostruzione paleoambientale, per la cronologia e per lo studio genetico di popolazioni nomadi e sedentarie della regione, forniscono una prima base analitica per ricostruire gli sviluppi culturali del Tardo Quaternario, dalla Middle Stone Age, attraverso la transizione Pleistocenee Olocene (facies Iberomaurusiano e Capsiano), fino al tardo Neolitico