Whole blood transcriptome signature predicts severe forms of COVID-19: Results from the COVIDeF cohort study.

COVID-19 is associated with heterogeneous outcome. Early identification of a severe progression of the disease is essential to properly manage the patients and improve their outcome. Biomarkers reflecting an increased inflammatory response, as well as individual features including advanced age, male gender, and pre-existing comorbidities, are risk factors of severe COVID-19. Yet, these features show limited accuracy for outcome prediction. The aim was to evaluate the prognostic value of whole blood transcriptome at an early stage of the disease. Blood transcriptome of patients with mild pneumonia was profiled. Patients with subsequent severe COVID-19 were compared to those with favourable outcome, and a molecular predictor based on gene expression was built. Unsupervised classification discriminated patients who would later develop a COVID-19-related severe pneumonia. The corresponding gene expression signature reflected the immune response to the viral infection dominated by a prominent type I interferon, with IFI27 among the most over-expressed genes. A 48-genes transcriptome signature predicting the risk of severe COVID-19 was built on a training cohort, then validated on an external independent cohort, showing an accuracy of 81% for predicting severe outcome. These results identify an early transcriptome signature of severe COVID-19 pneumonia, with a possible relevance to improve COVID-19 patient management.

Benzodiazepines for pediatric epilepsies and their risks in a cohort within the French health care data.

OBJECTIVE: The management of antiseizure treatment in patients with epilepsy relies on the benefit-risk ratio. Data on antiseizure medication (ASM) use in children are limited. We described antiseizure medication use in children with epilepsy (CwE) in France, with a focus on the chronic use of benzodiazepines and related implications. METHODS: We conducted a 5-year cohort study from January 2012, using data from the French national health care data system (Système National des Données de Santé). We included CwE identified through International Classification of Diseases, 10th Revision codes and medications from January 2012 to December 2015 and followed them until December 2016. We described ASMs and assessed whether the risk of initiating a polytherapy after a bitherapy depends on whether benzodiazepine was included in the bitherapy. RESULTS: We identified 62 885 CwE. Valproate was the most reimbursed ASM (40%), followed by lamotrigine (17.6%), levetiracetam (9.3%), clobazam (6.1%), and carbamazepine (5.8%). Prescriptions were initiated at the hospital in 74.5% of CwE. We observed a decrease in the number of CwE with at least one benzodiazepine reimbursement from 15.3% in 2013 to 10.1% in 2016 (p < .0001). The prevalence of CwE with levetiracetam reimbursements increased, whereas that of CwE with valproate decreased. A switch from a bitherapy to a polytherapy was more likely when the bitherapy included a benzodiazepine (subdistribution hazard ratio [sHR] = 1.20 [1.03-1.39]). SIGNIFICANCE: The prevalence of CwE with at least one benzodiazepine reimbursement decreased during the study period. Benzodiazepines were associated with an increased use of subsequent ASM polytherapy.

Amantadine use in the French prospective NS-Park cohort.

OBJECTIVE: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). BACKGROUND: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. METHODS: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). RESULTS: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. CONCLUSIONS: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

Ability to predict rheumatoid arthritis relapse after tumour necrosis factor inhibitor tapering by the Multi-Biomarker Disease Activity Score: a post-hoc analysis of the STRASS trial.

OBJECTIVES: The aim was to evaluate the ability of baseline multi-biomarker disease activity (MBDA) score to discriminate between patients with rheumatoid arthritis (RA) in remission who are at high risk versus low risk of relapse after TNF-inhibitor (TNFi) tapering. METHODS: The study is a post-hoc analysis of patients who completed the Spacing of TNFi injections in Rheumatoid ArthritiS Study (STRASS), a multicentre 18-month equivalence randomised controlled study, of TNFi tapering in RA patients in remission, and had baseline serum samples available for MBDA testing. The primary endpoint of this study was the ability of the baseline MBDA score to predict relapse at any time during the 18 months following initiation of TNFi tapering. Secondary endpoints were the ability of baseline MBDA score to predict TNFi discontinuation at Month 18, and structural damage progression on x-rays assessed by the change in total van der Heijde-modified Sharp score from baseline to month 18. RESULTS: 64 and 73 patients were included in the spacing (S)-arm and maintenance (M)-arm, respectively. In the M-arm, the mean MBDA score at baseline was higher among patients who relapsed during the 18-month follow-up than those who did not relapse: 32.5 compared to 27.2 (p=0.053) whereas no difference in the MBDA score was observed in the S-arm between patients who relapsed or not 27 compared to 26.2 (p=0.57) 13 patients (21.3%) of the S-arm were able to discontinue TNFi, for which the predictive value of the MBDA score was low (AUC=0.560). Radiographic progression in both arms, although low (n=9) was not correlated with the MBDA score at baseline with a poor discriminative value in both arms (AUC=0.558). CONCLUSIONS: In our study MBDA score in baseline was not predictive of relapse, discontinuation of TNFi in patients with long-standing RA patients tapering TNFi.

Clinical features, therapeutic choice and response by phototype in psoriasis: analysis of the French PsoBioTeq cohort.

BACKGROUND: Little is known about phototype and the response to systemic treatment in psoriasis. OBJECTIVES: To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype. METHODS: We included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12 months based on 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index (DLQI) 0/1. RESULTS: Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, and more frequently initiated ustekinumab. Patients in the V-VI group maintained the initial biologic prescribed as did the other phototype groups, even though the proportion of patients reaching PASI 90 and DLQI 0/1 at 12 months was lower in this group than the other groups. CONCLUSIONS: Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. The phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient.

In-hospital mortality of older patients with COVID-19 throughout the epidemic waves in the great Paris area: a multicenter cohort study.

BACKGROUND: Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19. METHODS: This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group's data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type. RESULTS: Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79-90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21-1.66] and 1.56 [95%CI 1.33-1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants. CONCLUSIONS: Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as "milder" but not "mild". This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.

Computerized decision support system (CDSS) use for surveillance of antimicrobial resistance in urinary tract infections in primary care.

BACKGROUND: Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care. OBJECTIVES: To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs. METHODS: We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections. RESULTS: We collected 43 591 Q-UTI, of which 10 192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%-42.2%) for amoxicillin, 16.6% (95% CI, 15.9%-17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%-7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%-6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value = 0.004), and in EARS-NET (55.2%, P value < 0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value < 0.001) and EARS-NET (15.8%, P value = 0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value < 0.001), but lower than in EARS-NET (9.5%, P value < 0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value < 0.001). CONCLUSIONS: CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC.

Fully automated opportunistic screening of vertebral fractures and osteoporosis on more than 150 000 routine computed tomography scans.

OBJECTIVE: Osteoporosis is underdiagnosed and undertreated, although severe complications of osteoporotic fractures, including vertebral fractures, are well known. This study sought to assess the feasibility and results of an opportunistic screening of vertebral fractures and osteoporosis in a large database of lumbar or abdominal CT scans. MATERIAL AND METHODS: Data were analysed from CT scans obtained in 35 hospitals from patients aged 60 years or older and stored in a Picture Archiving and Communication System in Assistance-Publique-Hôpitaux de Paris, from 2007 to 2013. Dedicated software was used to analyse the presence or absence of at least 1 vertebral fracture (VF), and the radiodensity of the lumbar vertebrae was measured Hounsfield Units (HUs). A simulated T-score was calculated. RESULTS: Data were analysed from 152 268 patients [mean age (S.D.) = 73.2 (9.07) years]. Success rates for VF assessment and HUs measurements were 82 and 87%, respectively. The prevalence of VFs was 24.5% and increased with age. Areas under the receiver operating characteristic curves for the detection of VFs were 0.61 and 0.62 for the mean HUs of the lumbar vertebrae and the L1 HUs, respectively. In patients without VFs, HUs decreased with age, similarly in males and females. The prevalence of osteoporosis (sT-score ≤ -2.5) was 23.8% and 36.5% in patients without and with VFs, respectively. CONCLUSION: It is feasible on a large scale to screen for VFs and osteoporosis during opportunistic screening in patients 60 years or older having lumbar or abdominal CT.

Real-life golimumab persitence in patients with axial spondyloarthritis: post-hoc results of the prospective observational cohort study, GO-PRACTICE.

OBJECTIVES: To evaluate in clinical practice the persistence and safety of golimumab, together with the evolution of disease activity and patient reported outcomes, in adult patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis (axSpA). This article focuses on the outcomes of golimumab treatment in axSpA patients. METHODS: Golimumab persistence 24 months after initial prescription (primary outcome) was assessed using Kaplan-Meier estimates. Secondary outcomes included evaluations of disease activity evolution (ASDAS and BASDAI), patient-reported outcomes (EQ-5D, SF-12 and HAQ), and golimumab's safety profile. RESULTS: Of 478 axSpA patients, 60.9% were biologic-naïve. Mean age and proportion of females were higher in biologics-pretreated patients (46.8 vs. 40.2 years, p<0.001 and 62.0% vs. 49.8%, p=0.009, respectively). Golimumab persistence at 24 months was 52.6% [95% CI 47.9-57.1%] in the axSpA cohort. It was 59.2% [95% CI 53.1-64.8%] and 42.7% [95% CI 35.3-49.8%] respectively, for biologics-naïve and biologics-pretreated patients (p<0.01), and 65.9% [95% CI 58.9-72.0%] and 41.5% [95% CI 35.2-47.6%], respectively for males and females (p<0.01). Reasons for golimumab discontinuation were primary non-response (37.4%), secondary non-response (24.8%) and intolerance (21.5%). Disease activity and patient reported outcomes improved significantly for those who persisted at 24 months and were higher for biologics-naïve patients. CONCLUSIONS: Golimumab persistence at 2 years in axSpA patients was 52.6%. Previous treatment with another biologic and female gender were associated with earlier discontinuation. Golimumab was a well-tolerated therapy for axSpA, with no new safety signals observed.

Impact of Childhood Onset Psoriasis on Addictive Behaviours, Socioeconomic and Educational Data in Adulthood.

Paediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease.

Evolution of Drug Survival with Biological Agents and Apremilast Between 2012 and 2018 in Patients with Psoriasis from the PsoBioTeq Cohort.

Drug survival reflects treatment effectiveness and safety in real life. There is limited data on the variation of drug survival with the availability of systemic treatments with additional biological disease-modifying antirheumatic drugs (bDMARDs) or synthetic disease-modifying antirheumatic drugs (sDMARDs). The aim of this study was to determine whether the increasing number of available systemic treatments for psoriasis affects drug survival over time. Patients were selected from the PsoBioTeq cohort, a French prospective observational cohort enrolling patients with moderate to severe psoriasis. All patients initiating a first bDMARD or sDMARD were included. The primary outcome was comparison of drug survival over time. A multivariate Cox proportional hazard ratio model was computed. A total of 1,866 patients were included; 739 females (39%), median age 47 years. In the multivariate Cox model, no association was found between the calendar year of initiation and drug survival (hazard ratio) overlapping from 0.80 (0.42-1.52) to 1.17 (0.64-2.17), p = 0.633). In conclusion, drug survival in psoriasis is not affected by the year of initiation.

Compassionate Use of Hydroxychloroquine in Clinical Practice for Patients With Mild to Severe COVID-19 in a French University Hospital.

BACKGROUND: Data from nonrandomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against coronavirus disease 2019 (COVID-19). METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe COVID-19 in a French university hospital. Patients who received hydroxychloroquine (200 mg 3 times daily dosage for 10 days) on a compassionate basis in addition to standard of care (SOC) were compared with patients without contraindications to hydroxychloroquine who received SOC alone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, obesity, National Early Warning Score 2 (NEWS2) score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed COVID-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOC alone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxychloroquine was not associated with a significantly reduced risk of unfavorable outcome (hazard ratio, 0.90 [95% confidence interval, .38-2.1], P = .81). Overall survival was not significantly different between the 2 groups (hazard ratio, 0.89 [0.23; 3.47], P = 1). CONCLUSION: In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC. Unmeasured confounders may have persisted however, despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of COVID-19. In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC.

Association Between Lack of Blinding and Mortality Results in Critical Care Randomized Controlled Trials: A Meta-Epidemiological Study.

OBJECTIVES: To investigate whether intervention effect estimates for mortality differ between blinded and nonblinded randomized controlled trials conducted in critical care. We used a meta-epidemiological approach, comparing effect estimates between blinded and nonblinded randomized controlled trials for the same research question. DATA SOURCES: Systematic reviews and meta-analyses of randomized controlled trials evaluating a therapeutic intervention on mortality in critical care, published between January 2009 and March 2019 in high impact factor general medical or critical care journals and by Cochrane. DATA EXTRACTION: For each randomized controlled trial included in eligible meta-analyses, we evaluated whether the trial was blinded (i.e., double-blinded and/or reporting adequate methods) or not (i.e., open-label, single-blinded, or unclear). We collected risk of bias evaluated by the review authors and extracted trial results. DATA SYNTHESIS: Within each meta-analysis, we compared intervention effect estimates between blinded and nonblinded randomized controlled trials by using a ratio of odds ratio (< 1 indicates larger estimates in nonblinded than blinded randomized controlled trials). We then combined ratio of odds ratios across meta-analyses to obtain the average relative difference between nonblinded and blinded trials. Among 467 randomized controlled trials included in 36 meta-analyses, 267 (57%) were considered blinded and 200 (43%) nonblinded. Intervention effect estimates were statistically significantly larger in nonblinded than blinded trials (combined ratio of odds ratio, 0.91; 95% CI, 0.84-0.99). We found no heterogeneity across meta-analyses (p = 0.72; I2 = 0%; τ2 = 0). Sensitivity analyses adjusting the main analysis on risk of bias items yielded consistent results. CONCLUSIONS: Intervention effect estimates of mortality were slightly larger in nonblinded than blinded randomized controlled trials conducted in critical care, but confounding cannot be excluded. Blinding of both patients and personnel is important to consider when possible in critical care trials, even when evaluating mortality.

Secukinumab and ustekinumab treatment in psoriatic arthritis: results of a direct comparison.

OBJECTIVES: To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. METHODS: In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. RESULTS: A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. CONCLUSION: In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

Impact of persistence with tumour necrosis factor inhibitors on healthcare resource utilization and costs in chronic inflammatory joint diseases.

AIM: To assess persistence with subcutaneous (SC) tumour necrosis factor (TNF) inhibitors as well as the impact of persistence on healthcare resource utilization (HCRU) and costs in patients with chronic inflammatory joint diseases. METHODS: In this cohort study using population-based French claims data (from 2011 to 2014), we measured persistence with SC TNF inhibitors within 12 months (M0-12) following treatment initiation in treatment-naïve and treatment-experienced users (divided into three cohorts: rheumatoid arthritis [RA], ankylosing spondylitis [AS] and psoriatic arthritis [PsA]). Persistent patients were propensity score matched to nonpersistent patients at M12. The impact of persistence status on HCRU and costs was assessed during M12-24. RESULTS: Of treatment-naïve (n = 3,804) and treatment-experienced (n = 2,279) users, only 56.1% and 46.8% were persistent at M12, respectively. Nonpersistent patients had more outpatient visits, computerized tomography scans, spine or joint magnetic resonance imaging procedures and disease-related hospitalizations, while persistent patients had more rheumatologist visits. Nonpersistent patients had lower drug costs but higher nondrug-related healthcare and hospitalization costs than persistent patients. In AS and PsA, overall healthcare costs were similar in persistent and nonpersistent patients. In RA, overall healthcare costs were lower in persistent patients (15,753€ vs 17,590€ in treatment-naïve and 17,622€ vs 21,177€ in treatment-experienced). CONCLUSION: Persistence with SC TNF inhibitors within first 12 months following treatment initiation was low in both treatment-naïve and treatment-experienced patients. Differences were observed in distribution of costs between persistent and nonpersistent patients, showing that nonpersistence with SC TNF inhibitors can lead to increased HCRU and higher costs.

Prevalence of hyposmia and hypogeusia in 390 COVID-19 hospitalized patients and outpatients: a cross-sectional study.

Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (n = 198), hospital outpatients seen during the previous month (n = 129), and all COVID-19-highly suspect patients in two primary health centers (n = 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers' outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.

Real-life persistence of golimumab in patients with chronic inflammatory rheumatic diseases: results of the 2-year observational GO-PRACTICE study.

OBJECTIVES: GO-PRACTICE aimed to evaluate the persistence, clinical response and safety of golimumab in adult patients with chronic inflammatory rheumatic disease. METHODS: Prospective observational study with 24 months of follow-up, involving 134 rheumatologists from public or private health establishments in France. The primary outcome was the persistence of golimumab 24 months after initial prescription. Cumulative persistence probabilities were determined from Kaplan-Meier estimates. Secondary outcomes included an evaluation of disease activity and golimumab safety profile. RESULTS: Of 754 consecutively recruited patients, 170 had rheumatoid arthritis (RA) (54.3 years, 74.1% female, 64.7% biologics-naïve), 106 had psoriatic arthritis (PsA) (48.1 years, 70% female, 66.0% biologics-naïve) and 478 had axial spondyloarthritis (axSpA) (42.8 years, 54.6% female, 60.9% biologics-naïve). Golimumab persistence at 2 years was 56.5%, 45.1% and 52.6%, respectively, in RA, PsA and axSpA groups. Persistence was higher in biologics-naïve (58.3%) than in biologics pre-treated patients (42.7%, p<0.01). For 362 patients continuing golimumab at 2 years, disease activity improved significantly from baseline to 2 years: mean 28-joint disease activity score for RA and PsA was lowered by 2.06 and 1.89 points, and mean ankylosing spondylitis disease activity score was lowered by 3.11 points (p<0.0001) for axSpA. Patient appreciation of disease activity also improved; 8.9% of discontinuations were due to intolerance. CONCLUSIONS: Golimumab persistence was satisfactory at 2 years and accompanied by improvements in clinical effectiveness in 362 patients continuing golimumab at 2 years. Golimumab was well tolerated and its safety profile was consistent with those reported in previous studies.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq.

BACKGROUND: Obesity is associated with an increased risk of psoriasis. OBJECTIVE: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis. METHODS: In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival. RESULTS: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36-56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10-4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23-2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04-2.19). CONCLUSION: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.

Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies.

AIMS: Two post-authorisation studies assessed the safety and persistence of patients' use of nalmefene. METHODS: The START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted 'all comers' without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities. RESULTS: START study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were 'goal reached' and 'drug cost'. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year. CONCLUSIONS: Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.