Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients

2015 ◽  
Vol 22 (4) ◽  
pp. 511-519 ◽  
Author(s):  
M Radaelli ◽  
L Moiola ◽  
F Sangalli ◽  
F Esposito ◽  
V Barcella ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neuromyelitis Optica ◽  
Close Monitoring ◽  
Disability Status ◽  
Caucasian Patients ◽  
Spectrum Disorders ◽  
High Level ◽  
Term Benefit

Objective: To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. Methods: This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. Results: At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 ( p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 ( p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. Conclusions: A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19+ B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia.

scholarly journals Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders

2021 ◽  
Vol 9 (1) ◽  
pp. e1100
Author(s):  
Marius Ringelstein ◽  
Ilya Ayzenberg ◽  
Gero Lindenblatt ◽  
Katinka Fischer ◽  
Anna Gahlen ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Interleukin 6 ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Class Iii ◽  
Disability Status ◽  
Interleukin 6 Receptor ◽  
Spectrum Disorders ◽  
The Brain

Background and ObjectivesTo evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).MethodsAnnualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab.ResultsPatients received TCZ for 23.8 months (median; interquartile range 13.0–51.1 months), with an IV dose of 8.0 mg/kg (median; range 6–12 mg/kg) every 31.6 days (mean; range 26–44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5–5) to 0 (range 0–0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0–5] to 0 [range 0–4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0–3.0] to 0.2 [range 0–2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy.DiscussionThis study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.

Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders

2020 ◽  
pp. 135245852090699
Author(s):  
K Bigaut ◽  
C Lambert ◽  
L Kremer ◽  
C Lebrun ◽  
M Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
First Episode ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Disability Status ◽  
Plane Transverse ◽  
Spectrum Disorders ◽  
Extensive Transverse Myelitis

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

scholarly journals P629 Long-term effectiveness and safety of ustekinumab (UST) in patients with active Crohn’s disease (CD) in real life: Interim analysis of the SUSTAIN study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S520-S522
Author(s):  
M Chaparro ◽  
S Sulleiro ◽  
I Bastón-Rey ◽  
C Rodríguez ◽  
I García-Tercero ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Predictive Factors ◽  
Cumulative Incidence ◽  
Retention Rate ◽  
Previous Surgery ◽  
Short Term ◽  
Term Benefit

Abstract Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (&gt;60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) &gt;4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

Long Term Follow-up and Optimization of Infliximab in Refractory Uveitis Due to Behçet’s Disease. National Study of 103 Caucasian Patients

2020 ◽  
pp. jrheum.200300
Author(s):  
José Luis Martín-Varillas ◽  
Belén Atienza-Mateo ◽  
Vanesa Calvo-Rio ◽  
Emma Beltrán ◽  
Juan Sánchez-Bursón ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cost Effective ◽  
National Study ◽  
Serious Adverse Events ◽  
Oral Ulcers ◽  
Long Term Follow Up ◽  
Caucasian Patients ◽  
The Comparative Study

Objective In a large series of Caucasian patients with refractory uveitis due to Behçet disease (BD) treated with infliximab (IFX) we assessed: a) long-term efficacy and safety and b) IFX optimization when ocular remission was achieved. Methods Multicenter study of IFX-treated patients with BD uveitis refractory to conventional immunosuppressant agents.103 patients/185 affected eyes were treated with IFX as first biologic therapy as follows: 3-5 mg/kg i.v. at 0, 2, 6 and then every 4-8 weeks. a) The main outcome variables were analyzed at baseline, 1st week, 1st and 6th months and 1st and 2nd years of IFX therapy. b) After remission, based on a shared decision between patient and clinician, IFX optimization was performed. Efficacy, safety, and cost of IFX therapy were evaluated. Results In whole series (n=103), main outcome variables showed a rapid and maintained improvement, reaching remission in 78 patients after a mean IFX duration of 31.5 months. Serious adverse events were observed in 9 patients: infusional reactions (n=4), tuberculosis (n=1), Mycobacterium avium pneumonia (n=1), severe oral ulcers (n=1), palmoplantar psoriasis (n=1) and colon carcinoma (n=1). In the optimization subanalysis, the comparative study between optimized and nonoptimized groups showed: a) no differences in clinical characteristics at baseline; b) similar maintained improvement in most ocular outcomes; and c) lower severe adverse events, and d) lower mean IFX costs in optimized group (4,826.52 vs. 9,854.13 euros/patient/year). Conclusion IFX seems to be effective and relatively safe in Caucasian patients with refractory BD uveitis. IFX optimization is effective, safe, and cost-effective.

OP270 Why The Haute Autorité de Santé Rejects the Widespread Use Of “Mini-Bypass”/One Anastomosis Gastric Bypass For Obesity In France

2020 ◽  
Vol 36 (S1) ◽  
pp. 4-4
Author(s):  
Jean-Charles Lafarge ◽  
Denis-Jean David ◽  
Cédric Carbonneil
Keyword(s):  
Esophageal Cancer ◽  
Gastric Bypass ◽  
Adverse Events ◽  
Severe Obesity ◽  
One Anastomosis Gastric Bypass ◽  
Close Monitoring ◽  
Efficacy And Safety ◽  
Multicenter Rct ◽  
Nutritional Complications

IntroductionOne anastomosis gastric bypass (OAGB) has become a widespread technique over the last few years in France, without any prior assessment and despite existing controversies among bariatric surgeons. An older bypass technique for treating obesity, the Roux-en-Y gastric bypass (RYGB), is available and reimbursed, having been assessed and approved for use in 2005. In 2019, the French Haute Autorité de Santé (HAS) assessed OAGB for the treatment of severe and massive obesity. This assessment, the first in the world, was undertaken for OAGBs carried out with a 200- or 150-centimeter biliopancreatic-limb (BP-limb) length.MethodsA systematic review (SR) of the literature and consultation of a working group consisting of both healthcare professionals (clinician and surgeons) and patients were carried out. The primary aim of our assessment was to determine whether the OAGB technique can replace RYGB. The efficacy and safety profile of OAGB was compared with RYGB in adult patients with massive, severe obesity. Complications and postoperative follow up specific to OAGB were identified.ResultsThe three selected randomized controlled trials (RCTs) could not confirm the superiority or the non-inferiority of OAGB, compared with RYGB, on the selected efficacy endpoints of weight loss, resolution of comorbidities, and quality of life. Adverse events reported for OAGB included severe nutritional complications and bile reflux that could potentially lead to lower esophageal cancer. In one RCT, the frequency of serious adverse events in the OAGB group was almost two times higher than in the RYGB group.ConclusionsHAS considered that OAGB carried out with a longer (200 centimeter) BP-limb is not a validated technique for the surgical treatment of massive, severe obesity. Thus, it cannot be considered an alternative to RYGB. There were insufficient data available on OAGB performed with a 150-centimeter BP-limb. Thus, HAS recommended undertaking a multicenter RCT to assess the efficacy and safety of OAGB. Patients who have already undergone OAGB should receive the same follow up as patients who have received RYGB, including close monitoring for nutritional complications and lower esophageal cancer and an endoscopic examination five years after surgery.

scholarly journals POS0815 CLINICAL CHARACTERISTICS, IMAGING PHENOTYPE, AND LONG-TERM OUTCOMES OF TAKAYASU ARTERITIS PATIENTS WITH HYPERTENSION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 661.1-661
Author(s):  
Y. Sun ◽  
L. Ma ◽  
H. Chen ◽  
C. Rongyi ◽  
L. Jiang
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Clinical Features ◽  
Takayasu Arteritis ◽  
Pressure Control ◽  
Free Survival ◽  
The World ◽  
Cluster 2

Background:Hypertension occurred in 30-80% of TAK patients around the world. The occurrence of hypertension might severely worsen TAK prognosis. Nevertheless, data describing the specific imaging features in hypertensive TAK patients and the associations between hypertensive severity, blood pressure control status and long-term outcome were still lacking.Objectives:To investigate the characteristics and associations of hypertensive characteristics with adverse events-free survival in Takayasu arteritis (TAK) patients with hypertension.Methods:This research was based on a prospectively on-going observational cohort-East China Takayasu Arteritis (ECTA) cohort. In all, 618 TAK patients, who registered in the ECTA cohort up to December 2019, were enrolled. The main outcome was the adverse-events-free survival among hypertensive TAK patients during the follow-up ended on August 2020.Results:Totally, 204 (33.0%) patients suffered from hypertension, with 48 (23.5%), 62 (30.4%), and 94 (46.1%) mild, moderate, and severe hypertension, respectively. Cluster analysis indicated three imaging phenotypes for hypertensive TAK patients: Cluster 1: involvement of the abdominal aorta and/or renal artery (n=56, 27.5%); Cluster 2: involvement of the ascending aorta, thoracic aorta, and the aortic arch and its branches (n=38, 18.6%); Cluster 3: combined involvement of Cluster 1 and Cluster 2 (n=111, 54.4%). By the end of the follow-up, the blood pressure control rate was 50.8%, while the adverse-events-free survival was 67.9% in the entire hypertensive population. Multivariate Cox regression analysis indicated that well-controlled blood pressure (HR=2.13, 95%CI 1.32–3.78, p=0.047), co-existence of severe aortic valve regurgitation (HR=0.87, 95%CI 0.64–0.95, p=0.043), Cluster 1 (HR=0.69, 95%CI 0.48–0.92, p=0.017) and Cluster 3 (HR=0.72, 95%CI 0.43–0.94, p=0.048) imaging phenotype was associated with the adverse-events-free survival.Conclusion:Patients with controlled hypertension showed better adverse-events-free survival, while those with the Cluster 1 imaging phenotype were more likely to suffer from worse adverse-events-free survival. Hypertension occurred in 30-80% of TAK patients around the world. The occurrence of hypertension might severely worsen TAK prognosis.References:[1]Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: a review. J Clin Pathol 2002; 55:481–6.[2]Watanabe Y, Miyata T, Tanemoto K. Current clinical features of new patients with Takayasu arteritis observed from a cross-country research in Japan: age and sex specificity. Circulation 2015; 132:1701–9.[3]Yilmaz N, Can M, Oner FA, et al. Impaired quality of life, disability and mental health in Takayasu’s arteritis. Rheumatol. (Oxford) 2013; 52:1898–904.[4]Laurent A, Julien H, Nicolas L, et al. Takayasu arteritis in France: a single-center retrospective study of 82 cases comparing white, North African, and black patients. Medicine 2010; 89:1–17.[5]Mwipatayi BP, Jeffery PC, Beningfield SJ, et al. Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg 2005; 75:110–7.Disclosure of Interests:None declared

Ultrasound Biomicroscopy Documented Anterior Uveal Melanoma Regression after Ruthenium-106 Plaque Therapy

2021 ◽  
pp. 1-9
Author(s):  
Biljana Kuzmanović Elabjer ◽  
Mladen Bušić ◽  
Andrej Pleše ◽  
Mirjana Bjeloš ◽  
Daliborka Miletić ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Tumor Regression ◽  
Corneal Thickness ◽  
Case Series ◽  
Ultrasound Biomicroscopy ◽  
Close Monitoring ◽  
Single Institution ◽  
Retrospective Case ◽  
Caucasian Patients

<b><i>Introduction:</i></b> Ultrasound biomicroscopy (UBM) is the only widely used method for the evaluation of anterior uveal melanoma (AUM). <b><i>Objective:</i></b> Documentation of regression of AUM treated with ruthenium-106 (Ru-106) plaque types CCB and CCC using UBM. <b><i>Methods:</i></b> This single institution-based retrospective case series involved 10 Caucasian patients with AUM followed after brachytherapy with UBM from January 2014 until February 2019. The largest prominence of the tumor perpendicular to the sclera or the cornea (including scleral/corneal thickness) (<i>D</i>) and the largest basal dimension (<i>B</i>) were measured in millimeters with UBM for all patients prior to the brachytherapy and at 4-month interval follow-up. Tumor regression was calculated as a percentage of decrease in the initial <i>D</i> and <i>B</i> values. <b><i>Results:</i></b> The study involved 10 patients with a mean age of 64.4 years (yr) (range 46–80 yr). <i>D</i> ranged from 1.82 to 5.5 mm (median 2.99 mm) and <i>B</i> from 2.32 to 12.38 mm (median 4.18 mm). The apical radiation dose in all patients was 100 Gy. The median follow-up was 42.02 months. Regression for <i>D</i> was 21.11 ± 13.66%, 31.09 ± 14.66%, and 34.92 ± 19.86% at 1st, 2nd, and 3rd year of the follow-up, respectively, while for <i>B</i> it was 21.58 ± 16.05%, 28.98 ± 17.71%, and 32.06 ± 18.96%, respectively. Tumor recurrence was documented in 2/10 patients. <b><i>Conclusion:</i></b> The major regression of AUM, treated with Ru-106 plaque types CCB and CCC, was documented in the first 2 years after brachytherapy in our study group. In the following years, only minimal regression was documented that warns of the need for close monitoring and active search for local recurrences.

scholarly journals Physical workload and increased frequency of musculoskeletal pain: a cohort study of employed men and women with baseline occasional pain

2021 ◽  
pp. oemed-2020-107094
Author(s):  
Kathryn Badarin ◽  
Tomas Hemmingsson ◽  
Lena Hillert ◽  
Katarina Kjellberg
Keyword(s):  
Survey Data ◽  
Musculoskeletal Pain ◽  
Leisure Time Physical Activity ◽  
Physical Workload ◽  
Job Exposure Matrix ◽  
Men And Women ◽  
Strenuous Work ◽  
High Level

ObjectivesMusculoskeletal pain (MSP) is prevalent among the workforce. This study investigates the long-term association between physical workload (PWL) and increased frequency of MSP among male and female employees with pre-existing occasional MSP.MethodsThis study uses the Stockholm Public Health cohort survey data from the baseline 2006. The sample includes 5715 employees with baseline occasional MSP (no more than a few days per month). Eight PWL exposures and overall PWL were estimated using a job-exposure matrix (JEM). The JEM was assigned to occupational titles from a national register in 2006. Follow-up survey data on frequent MSP (a few or more times a week) were collected from 2010. Logistic regressions produced sex-specific ORs with 95% CIs and were adjusted for education, health conditions, psychological distress, smoking, BMI, leisure-time physical activity and decision authority.ResultsAssociations were observed between several aspects of heavy PWL and frequent MSP for men (eg, OR 1.57, 95% CI 1.13 to 2.20, among those in the highest exposure quartile compared with those in the lowest quartile for heavy lifting) and women (eg, OR 1.76, 95% CI 1.35 to 2.29, among those in the highest exposure quartile compared with those in the the lowest quartile for physically strenuous work). Small changes were observed in the OR after adjustment, but most of the ORs for PWL exposures among the men were no longer statistically significantly increased.ConclusionA high level of exposure to heavy PWL was associated with increased frequency of MSP 4 years later for men and women with baseline occasional pain.

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