AbbVie (Ireland)

IntroductionTo evaluate real-life efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in posterior segment inflammation due to non-infectious uveitis (treatment-naïve or not) in French clinics.MethodsIn this prospective, multicenter, observational, non-comparative, post-reimbursement study, consecutive patients with posterior segment inflammation due to non-infectious uveitis were enrolled and evaluated at baseline (day 0). Those who received DEX on day 0 were re-evaluated at months 2, 6, and 18. Retreatment with DEX and/or alternative therapies was allowed during follow-up. Primary outcome: patients (%) with at least a 15-letter gain in best corrected visual acuity (BCVA) at 2 months. Secondary outcomes included patients (%) with at least 15-letter BCVA gains at 6 and 18 months; mean BCVA change from baseline at 2, 6, and 18 months; and patients (%) retreated, mean central retinal thickness (CRT), and adverse events (AEs) at all post-baseline visits.ResultsNinety-seven of 245 enrolled patients with posterior segment inflammation due to non-infectious uveitis (80% previously treated) and disease duration of 5 years (average) received DEX on day 0 and were included in efficacy analyses. At month 2 (n = 91), 20.5% of patients (95% CI 12.0–28.9) gained at least 15 letters from a baseline mean of 60.9 letters; the mean gain was 6.2 letters (95% CI 3.5–8.9). At month 6, 50.0% (n = 38/76) of patients did not receive alternative treatment or DEX retreatment, mostly because inflammation had sufficiently subsided (n = 27/38, 71.1%). Although early study termination prevented efficacy analysis at 18 months (n = 12), CRT reductions persisted throughout follow-up. From baseline to month 18, 21/245 (8.6%) patients had DEX-related AEs; 17/245 (6.9%) had ocular hypertension (most common AE).ConclusionLOUVRE 2 confirms DEX efficacy on visual acuity and CRT in predominantly DEX-pretreated patients with relatively old/stabilized uveitis. DEX tolerability was consistent with known/published data, confirming treatment benefits in posterior segment inflammation due to non-infectious uveitis.ClinicalTrials.gov IdentifierNCT02951975.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00525-8.

BackgroundLupus low disease activity state (LLDAS) attainment has been reported to be associated with reduced damage accrual, flare, and mortality, as well as improved quality of life, in cohorts of SLE patients with established disease. Whether these associations are present in recent-onset disease is less well known.ObjectivesTo evaluate the associations of LLDAS attainment with outcomes in patients with recent onset SLE.MethodsData from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected prospectively between 2013 and 2020 using standard templates. Organ damage and flare were captured using SLICC Damage Index and SELENA-SLEDAI Flare Index, respectively. LLDAS was defined as Golder et al., 2019 [1]. An inception cohort was defined based on duration since SLE diagnosis<1 year at enrolment. Patient characteristics between inception and non-inception cohorts were compared using Wilcoxon rank-sum (continuous variables) or Pearson’s Chi-squared tests (categorical variables). Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare.ResultsThe study cohort included 4,106 patients of whom 680 (16%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the non-inception cohort, inception cohort patients were significantly younger, had higher disease activity (SLEDAI-2K and physician global assessment), used more glucocorticoids and immunosuppressants but had less organ damage at enrolment and only 88 (13.6%) patients accrued damage during a median 2.2 years follow-up (Table 1).Table 1.Non-inception cohortInception cohortp-valuen=3426n=680Age at enrolment (years), median [IQR]40 [31, 51]33 [25, 44]<0.001Age at diagnosis (years), median [IQR]28 [21, 38]33 [25, 43]<0.001SLE duration at enrolment (years), median [IQR]10 [5, 16]1 [0, 1]<0.001Study duration (years), median [IQR]2.5 [1.0, 5.4]2.2 [0.9, 3.7]<0.001Females, n (%)3155 (92.1%)623 (91.6%)0.68Asian ethnicity, n (%)3037 (89.1%)595 (88.1%)0.49Prednisolone (PNL) use - ever, n (%)2865 (83.6%)620 (91.2%)<0.001Time adjusted mean (TAM)-PNL, median [IQR]5.0 [2.2, 8.6]6.2 [3.2, 10.3]<0.001Cumulative PNL (g), median [IQR]3.4 [0.5, 9.7]3.8 [1.1, 8.5]0.26Anti-Malarial use - ever, n (%)2669 (77.9%)569 (83.7%)<0.001Immunosupressant use -ever, n (%)2367 (69.1%)521 (76.6%)<0.001AMS (TAM-SLEDAI-2K), median [IQR]2.8 [1.2, 4.6]3.1 [1.6, 5.0]0.002TAM-PGA, median [IQR]0.4 [0.2, 0.7]0.4 [0.3, 0.8]<0.001Mild/moderate/severe flare ever, n (%)1789 (52.2%)391 (57.5%)0.012Organ damage accrual, n (%)629 (20.8%)88 (13.6%)<0.001LLDAS at baseline, n (%)1730 (50.5%)195 (28.7%)<0.001LLDAS-ever (at least once), n (%)2637 (78.2%)492 (73.9%)0.014≥50% time in LLDAS (LLDAS-5), n (%)1612 (50.6%)256 (41.1%)<0.001Significantly fewer inception cohort patients were in LLDAS at enrolment than the non-inception cohort (29% vs. 51%, p<0.001). However, 74% of inception and 78% of non-inception cohort patients achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrolment, time to first LLDAS attainment was assessed: inception cohort patients were 60% more likely to attain their first LLDAS (HR = 1.60 (95%CI: 1.40, 1.82), p<0.001) than non-inception cohort patients. LLDAS attainment was significantly protective against flare in the inception (HR, 95% CI) and non-inception (HR, 95% CI) cohorts. Trends towards protection against damage accrual in association with LLDAS in the inception cohort were not significant.ConclusionLLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed, due to low rates of damage accrual in the first years after SLE diagnosis.

To collect real-world data to gain improved understanding of safety, tolerability, and potential benefits of adding CGRP monoclonal antibody therapy (CGRPmAb) to onabotulinumtoxinA treatment in patients with chronic migraine (CM).

Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB. Fifty-nine children aged 3 to <18 years hepatitis B e antigen-positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group. Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events. The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.

BackgroundWomen with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancer. The decision to embark on risk reduction strategies is a difficult and personal one. We surveyed an international group of women with BRCA mutations and measured choices and sequence of breast cancer risk reduction strategies.MethodsWomen with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the US, Canada, the UK, Australia, and from a national advocacy group. Using an online survey, we asked about cancer-risk reduction preferences including for one of two hypothetical medicines, randomly assigned, and women’s recommendations for a hypothetical woman (Susan, either a 25- or 36-year-old). Sunburst diagrams were generated to illustrate hierarchy of choices.ResultsAmong 598 respondents, mean age was 40.9 years (range 25–55 years). Timing of the survey was 4.8 years (mean) after learning their positive test result and 33% had risk-reducing bilateral salpingo-oophorectomy (RRBSO) and bilateral mastectomy (RRBM), while 19% had RRBSO only and 16% had RRBM only. Although 30% said they would take a hypothetical medicine, 6% reported taking a medicine resembling tamoxifen. Respondents were 1.5 times more likely to select a hypothetical medicine for risk reduction when Susan was 25 than when Susan was 36. Women assigned to 36-year-old Susan were more likely to choose a medicine if they had a family member diagnosed with breast cancer and personal experience taking tamoxifen.ConclusionsWomen revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women with BRCA1 or BRCA2 mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical.

Severe infection of infants with respiratory syncytial virus (RSV) is a leading cause of morbidity in the developed world and mortality in the developing world. Prophylaxis using palivizumab in infants at risk for severe RSV disease reduces the rate of hospitalisation in this population of children. To ensure complete prophylaxis, infants must receive monthly doses over the winter season. To improve parental convenience, the Synacare® programme was implemented in Ireland and the Netherlands. Synacare® is now a longstanding programme in which palivizumab is administered in the home setting by skilled nurses. Protocols and procedures described here illustrate the efficiency and acceptability of the home delivery service of RSV disease prophylaxis. Post-administration surveys have indicated a high level of parental satisfaction with the programme. At-home paediatric programmes like Synacare® may serve as an alternative to burdensome monthly hospital visits and may lead to enhanced clinical outcomes.