Summary
Background
Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing ...steroid‐related adverse events (AEs) is unproven.
Objectives
To utilize data collected in a French investigator‐initiated, phase III, open‐label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV.
Methods
This was an independently conducted post hoc analysis of the moderate‐to‐severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg−1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg−1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24‐month efficacy and safety results were also reported.
Results
At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab‐plus‐prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS‐related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone.
Conclusions
In patients with moderate‐to‐severe PV, rituximab plus short‐term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life‐threatening CS‐related AEs.
What's already known about this topic?
Pemphigus vulgaris (PV) is the most common type of pemphigus.
Corticosteroids, a standard first‐line treatment for PV, have significant side‐effects.
Although their effects are unproven, adjuvant corticosteroid‐sparing agents are routinely used to minimize steroid exposure and corticosteroid‐related side‐effects.
There is evidence that the anti‐CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus.
What does this study add?
This study provides a more detailed analysis of patients with PV enrolled in an investigator‐initiated trial.
Rituximab plus prednisone had a steroid‐sparing effect and more patients achieved complete remission off prednisone.
Fewer patients experienced grade 3 or grade 4 steroid‐related adverse events than those on prednisone alone.
This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate‐to‐severe PV.
Linked Comment: Scorer et al. Br J Dermatol 2020; 182:1078–1079.
Objective. To evaluate the efficacy of resistance exercises in RA patients.
Methods. A systematic literature search was done using Pubmed, Embase and Cochrane databases through November 2009 and in ...abstracts presented at rheumatology scientific meetings over the past 3 years. Randomized controlled trials (RCTs) comparing resistance exercise based therapy with interventions without resistance exercise for the treatment of RA patients were included. Outcomes studied were post-intervention disability on the HAQ, functional capacity assessed by walking speed, pain on the visual analogue scale (VAS), joint count, isometric, isokinetic and grip strength. Efficacy was assessed by weighted mean differences (WMDs) and tolerance was assessed by relative risk (RR). Data were pooled using the inverse of variance model, and heterogeneity was tested.
Results. Ten RCTs, including 547 patients, met the study inclusion criteria. The mean (S.D.) Jadad score was 2.3 (0.6). Resistance exercises significantly improved isokinetic strength (WMD = 23.7%, P < 0.001), isometric strength (WMD = 35.8%, P < 0.001), grip strength (WMD = 26.4%, P < 0.001) and HAQ (WMD = −0.22, P < 0.001). Exercise also had a positive impact on the 50-foot walking test (WMD = −1.90 s, P < 0.001) and ESR (WMD = −5.17, P = 0.005). Withdrawals RR = 0.95, 95% confidence interval (CI) 0.61, 1.48 and adverse events (RR = 1.08, 95% CI 0.72, 1.63) were well balanced in both groups. Patient and exercise characteristics did not influence the results. Subgroup analysis revealed a trend towards higher efficacy associated with high-intensity programmes.
Conclusion. Resistance exercise in RA is safe, and the improvement in most outcomes was statistically significant and possibly clinically relevant for RA disability.
In studies investigating the effects of endocrine disruptors (ED) such as phthalates, bisphenols and some pesticides on human health, exposure is usually characterized with urinary metabolites. The ...variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment.
This study was conducted to assess variability of urinary metabolites of ED, and to investigate how sampling time and number of samples analyzed impacts exposure assessment.
Urine samples were collected over 6 months from 16 volunteers according to a random sampling design, and analyzed for 16 phthalate metabolites, 9 pesticide metabolites and 4 bisphenols. The amount of biomarkers excreted in urine at different times of the day were compared. In parallel, 2 algorithms were developed to investigate the effect of the number of urine samples analyzed per subject on exposure assessment reliability.
In the 805 urine samples collected from the participants, all the biomarkers tested were detected, and 18 were present in >90% of the samples. Biomarkers variability was highlighted by the low intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51. Comparing the amount of biomarkers excreted in urine at different time did not allow to identify a preferred moment for urine collection between first day urine, morning, afternoon and evening. Algorithms demonstrated that between 10 (for monobenzyl (MBzP) phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure.
The results illustrate the high variability of urinary biomarkers of ED over time and the impossibility to reliably classify subjects based on a single urine sample (or a limited number). Results showed that classifying individuals based on urinary biomarkers requires several samples per subject, and this number is highly different for different biomarkers.
Display omitted
•805 urine samples were collected over 6 months from 16 volunteers.•16 phthalate metabolites, 4 bisphenols and 9 pesticide metabolites were analyzed.•21 of the 29 fast elimination biomarkers were detected in >80% of samples.•No evidence to prefer a specific time of day for sample collection was observed.•High variability over time was observed for all the urinary biomarkers.
Notre objectif était d’évaluer l’évolution de la performance du diagnostic anténatal (DAN) des cardiopathies congénitales (CC) graves et sa qualité sur une période de 15
ans.
Analyse rétrospective de ...toutes les CC observées entre 2000 et 2005 (période 3) dans une population limitée au département d’Indre-et-Loire ; comparaison aux études réalisées de 1991 à 1994 (période 1) et de 1995 à 1999 (période 2). Les CC considérées comme détectables (CCD) étaient les CC majeures à révélation néonatale. La qualité a été évaluée en classant les DAN selon qu’ils étaient exacts, erronés ou incomplets.
Exactement 65,7 % des CCD ont été dépistées. Selon les critères de la période 1, le taux de dépistage est passé de 43,2 % (période 1) à 66,7 % (période 2), puis à 78 % (période 3). Entre les périodes 2 et 3, pour les CCD par une coupe 4 cavités et par une coupe sur les gros vaisseaux, ce taux est passé respectivement de 63 à 71 % et de 52 à 74 %. Au cours de la période 3, les diagnostics étaient exacts dans 80 % des cas s’ils étaient réalisés par un cardiopédiatre ; sinon, dans moins de 25 % des cas.
Notre étude montre une augmentation du taux de DAN des CC. Cependant, environ un tiers des CC majeures de la période néonatale n’a pas été diagnostiqué avant la naissance.
The value of prenatal diagnosis of major congenital heart diseases (CHDs) has already been proved. In this study, we observed the evolution of the detection rate of CHDs and the quality of the diagnoses over a 15-year period in the Indre-et-Loire department of France.
Retrospective analysis of the quantitative and qualitative data of prenatal diagnosis between 2000 and 2005 (period 3) and comparison with studies conducted from 1991 to 1994 (period 1) and from 1995 to 1999 (period 2). The CHDs considered to be detectable are the major CHDs with neonatal symptoms. In order to analyze the quality of prenatal diagnosis, each diagnosis was classified as correct, false, or incomplete during period 3.
Period 3: 65.7% detectable CHDs were screened. Using period 1 criteria for prenatal diagnosis, the percentage of CHDs detected for periods 1, 2, and 3 was 43.2, 66.7, and 78%, respectively. Between periods 2 and 3, the detection rate increased from 52 to 74% for CHDs diagnosed with the visualization of the outflow tract. It increased from 63 to 71% for CHDs diagnosed with a four-chamber view. During period 3, diagnoses made by a pediatric cardiologist were correct and complete in 80% of cases. It was less than 25% otherwise.
The improvement of prenatal diagnosis over time results from technological progress, the greater experience of ultrasonographers, and the systematic visualization of the outflow tract in addition to the four-chamber view. Despite the improvement in prenatal diagnosis, one-third of major CHDs were not screened before birth. Pediatricians still need to diagnose CHDs after birth.
Summary
Background
The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity.
Objectives
The objective of this ...study was to calculate BPDAI cut‐off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti‐BP180 and anti‐BP230 antibodies.
Methods
Severity scores were recorded by two blinded investigators. Anti‐BP180 and anti‐BP230 antibodies were measured using an enzyme‐linked immunosorbent assay (ELISA). Cut‐off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score.
Results
In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0–164). Cut‐off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 interquartile range (IQR) 17–45, and for patients with > 10 daily new blisters the median score was 55 (IQR 39–82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti‐BP180 ELISA value (Spearman’s rank r = 0·34, P < 0·004), but not with anti‐BP230 antibodies (r = 0·17, P = 0·15).
Conclusions
This study suggests cut‐off values of 20–57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.
What is already known about this topic?
The Bullous Pemphigoid Disease Area Index (BPDAI) is a new scoring system to measure bullous pemphigoid (BP) activity.
The use of this score in clinical practice is limited by the absence of cut‐off values.
What does this study add?
Cut‐off values of 20 and 57 were established to distinguish mild, moderate and severe BP using the BPDAI.
These disease activity subgroups could help physicians in the management of patients with BP.
What are the clinical implications of this work?
This study classified patients with BP into three subgroups (mild, moderate and severe) based on the BPDAI score.
The BPDAI score is a robust tool to assess BP activity accurately, both at diagnosis and during the course of the disease, and could help physicians tailor treatment to disease activity, thereby providing better management of patients with BP.
Linked Comment: Blome and Klein. Br J Dermatol 2021; 184:997–998.
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