Abatacept in the Treatment of Severe, Longstanding, and Refractory Uveitis Associated with Juvenile Idiopathic Arthritis

2015 ◽  
Vol 42 (4) ◽  
pp. 706-711 ◽  
Author(s):  
Christoph Tappeiner ◽  
Elisabetta Miserocchi ◽  
Bahram Bodaghi ◽  
Kaisu Kotaniemi ◽  
Friederike Mackensen ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Immunosuppressive Treatment ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Ocular Complications ◽  
Systemic Corticosteroids ◽  
Before And After ◽  
Active Arthritis ◽  
Factor Α ◽  
Antigen Presenting

Objective.Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA).Methods.Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor–α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications.Results.In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup.Conclusion.A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

scholarly journals Safety and Efficacy of Infliximab and Adalimumab for Refractory Uveitis in Juvenile Idiopathic Arthritis: 1-year Followup Data from the Italian Registry

2012 ◽  
Vol 40 (1) ◽  
pp. 74-79 ◽  
Author(s):  
MARIA E. ZANNIN ◽  
CAROLINA BIROLO ◽  
VALERIA M. GERLONI ◽  
ELISABETTA MISEROCCHI ◽  
IRENE PONTIKAKI ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Remission Rate ◽  
Immunosuppressive Treatment ◽  
Treatment Change ◽  
Ocular Complications ◽  
Safety And Efficacy ◽  
Patient Reported ◽  
Factor Α ◽  
Chronic Course ◽  
Necrosis Factor

Objective.To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis (JIA-AU).Methods.Starting January 2007, patients with JIA-AU treated with IFX and ADA were managed by a standard protocol and data were entered into the National Italian Registry (NIR). At baseline, all patients were refractory to standard immunosuppressive treatment and/or were corticosteroid-dependent. Data recorded every 3 months included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change or withdrawal, and laboratory measures. Data of patients treated for at least 1 year were retrieved from the NIR and analyzed using descriptive statistics. Treatment efficacy was based on change in uveitis course and in number of ocular complications.Results.Up to December 2009, data for 108 patients with JIA-AU treated with anti-tumor necrosis factor-α agents were recorded in the NIR and data from 91, with at least 12 months’ followup, were included in the study. Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients (55.3%) achieved remission of AU, 28 (32.9%) had recurrent AU, and 10 (11.8%) maintained a chronic course. A higher remission rate was observed with ADA (67.4% vs 42.8% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32 per subject. Five patients experienced resolution of structural complications. No patient reported serious AE; 8 (8.8%) experienced 11 minor AE (9 with IFX, 2 with ADA).Conclusion.IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period.

scholarly journals Use of connected digital products in clinical research following the COVID-19 pandemic: a comprehensive analysis of clinical trials

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e047341
Author(s):  
Caroline Marra ◽  
William J Gordon ◽  
Ariel Dora Stern
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Outcome Measures ◽  
Remote Monitoring ◽  
Search Algorithm ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Digital Products ◽  
Clinical Trial Registry ◽  
Before And After

ObjectivesIn an effort to mitigate COVID-19 related challenges for clinical research, the US Food and Drug Administration (FDA) issued new guidance for the conduct of ‘virtual’ clinical trials in late March 2020. This study documents trends in the use of connected digital products (CDPs), tools that enable remote patient monitoring and telehealth consultation, in clinical trials both before and after the onset of the pandemic.DesignWe applied a comprehensive text search algorithm to clinical trial registry data to identify trials that use CDPs for remote monitoring or telehealth. We compared CDP use in the months before and after the issuance of FDA guidance facilitating virtual clinical trials.SettingAll trials registered on ClinicalTrials.gov with start dates from May 2019 through February 2021.Outcome measuresThe primary outcome measure was the overall percentage of CDP use in clinical trials started in the 10 months prior to the pandemic onset (May 2019–February 2020) compared with the 10 months following (May 2020–February 2021). Secondary outcome measures included CDP usage by trial type (interventional, observational), funder type (industry, non-industry) and diagnoses (COVID-19 or non-COVID-19 participants).ResultsCDP usage in clinical trials increased by only 1.65 percentage points, from 14.19% (n=23 473) of all trials initiated in the 10 months prior to the pandemic onset to 15.84% (n=26 009) of those started in the 10 months following (p<0.01). The increase occurred primarily in observational studies and non-industry funded trials and was driven entirely by CDP usage in trials for COVID-19.ConclusionsThese findings suggest that in the short-term, new options created by regulatory guidance to stimulate telehealth and remote monitoring were not widely incorporated into clinical research. In the months immediately following the pandemic onset, CDP adoption increased primarily in observational and non-industry funded studies where virtual protocols are likely medically necessary due to the participants’ COVID-19 diagnosis.

scholarly journals Juvenile idiopathic arthritis-associated uveitis in the era of biological therapy: how the disease changed in more than 20 years of observation in a tertiary referral center in Rome (Italy)

2021 ◽  
Author(s):  
E. Del Giudice ◽  
C. Simio ◽  
A. Scala ◽  
A. Di Coste ◽  
G. La Torre ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Biological Therapy ◽  
Ocular Complications ◽  
Tertiary Referral Center ◽  
The Past ◽  
Systemic Corticosteroids ◽  
Band Keratopathy ◽  
Current Therapies ◽  
Disease Modifying ◽  
Care Improvement

Abstract Objectives To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis. Methods Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy. Results The total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047). Conclusion Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.

Comparison of Varying Bolus Doses of Oxytocin in Patients Undergoing Caesarean Spinal Delivery

2020 ◽  
Vol 10 (4) ◽  
pp. 261-265
Author(s):  
Muhammad Maqbool ◽  
Huda Shafqat
Keyword(s):  
Side Effects ◽  
Bolus Dose ◽  
Uterine Contraction ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Epigastric Discomfort ◽  
Hemodynamic Variables ◽  
Before And After ◽  
Oxytocin Infusion ◽  
Elective Cesarean

Objective: To determine the lowest effective bolus dose of oxytocin to produce adequate uterine tone during elective caesarean delivery avoiding side effects. Study design and setting: A study was conducted at Rawal General and Dental Hospital, from 10th Oct, 2018 to 27th May, 2019. Methodology: Patients undergoing elective cesarean spinal delivery were randomly divided by computer generated numbers(n=155) into 5 groups A, B, C, D and E receiving 0.5, 1, 3, 5 and 10 units of injection oxytocin as bolus respectively after delivery of baby. Uterine contraction was assessed by gynecologist by manual palpation of uterus on a linear scale. Value of 8 was considered adequate and 8 inadequate uterine tone respectively. Heart rate, non-invasive blood pressure and oxygen saturation were noted before and after oxytocin bolus. All patients received oxytocin infusion. The primary outcome measure was the assessment of uterine tone at 2 minute of oxytocin bolus. The secondary outcome variables included shortness of breath, chest discomfort, top-up bolus administered, hemodynamic variables, epigastric discomfort and oxytocin related effects (tachycardia, epigastric discomfort and hypotension). Results: The use of 5 units oxytocin (group-D) showed most optimal uterine contractions, 61.3% in comparison to commonly used 10 units bolus dose (group-E) 48.4% with minimal side effects like, less tachycardia(12.9% versus 72.9%) and hypotension (12.9% versus 32.3%), no top-up bolus dose was required in 54.8% cases and no complain of epigastric discomfort was observed. Conclusion: Low doses of oxytocin are effective in terms of uterine contraction with minimal side effects

Evidence for Tocilizumab as a Treatment Option in Refractory Uveitis Associated with Juvenile Idiopathic Arthritis

2016 ◽  
Vol 43 (12) ◽  
pp. 2183-2188 ◽  
Author(s):  
Christoph Tappeiner ◽  
Marina Mesquida ◽  
Alfredo Adán ◽  
Jordi Anton ◽  
Athimalaipet V. Ramanan ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Macular Edema ◽  
Therapeutic Option ◽  
Disease Onset ◽  
Systemic Corticosteroids ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Final Followup ◽  
Factor Α ◽  
Necrosis Factor

Objective.To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA).Methods.Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy.Results.A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit.Conclusion.TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.

A Feasibility Study of the Effect of Intra-Articular Corticosteroid Injection on Isokinetic Muscle Strength in Children With Juvenile Idiopathic Arthritis

2013 ◽  
Vol 25 (2) ◽  
pp. 221-237 ◽  
Author(s):  
Damien McKay ◽  
Genevieve Ostring ◽  
Carolyn Broderick ◽  
Jeffrey Chaitow ◽  
Davinder Singh-Grewal
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Muscle Strength ◽  
Corticosteroid Injection ◽  
Knee Extensor ◽  
Isokinetic Dynamometry ◽  
Isokinetic Muscle Strength ◽  
Peak Knee ◽  
Before And After ◽  
Active Arthritis ◽  
Flexor Strength

This study assessed the magnitude of changes in isokinetic muscle strength in children with juvenile idiopathic arthritis (JIA) before and after treatment with intra-articular corticosteroid injection and assessed the feasibility of a larger study of the same effect. Isokinetic dynamometry was used to measure peak knee extension and flexion torque in 12 children before and after treatment for unilateral knee arthritis. Extensor and flexor strength was reduced on the affected side before treatment (-0.56Nm/kg, p = .004 and −0.24Nm/kg, p = .02 respectively). Increases in extensor strength were observed at two weeks (p = .01) and twelve weeks postinjection (p = .03). Improvements at 6 weeks approached but did not reach statistical significance (p = .17). Improvements in flexor strength were not observed until 12 weeks postinjection (p = .03). Despite significant improvements in extensor strength, low peak knee extensor torque continued to be observed at 12 weeks (p = .01). Knee extensor and flexor strength is reduced in children with JIA with active arthritis and improves following intra-articular corticosteroid injection. Significant improvements in knee extensor and flexor strength were seen postinjection; however deficits in extensor strength were still evident at three months. Isokinetic dynamometry was safe and well tolerated in our sample of children with JIA with active arthritis.

scholarly journals Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

2018 ◽  
Vol 45 (8) ◽  
pp. 1167-1172 ◽  
Author(s):  
Vanessa Cecchin ◽  
Maria Elisabetta Zannin ◽  
Daniele Ferrari ◽  
Irene Pontikaki ◽  
Elisabetta Miserocchi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Remission Rate ◽  
Immunosuppressive Treatment ◽  
Dependent Data ◽  
Treatment Modalities ◽  
Ocular Complications ◽  
Safety And Efficacy ◽  
Standardized Protocol ◽  
Tnf Α ◽  
Treatment Switch

Objective.Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years.Methods.Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics.Results.Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX.Conclusion.At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

scholarly journals Juvenile idiopathic arthritis-associated uveitis in the era of biological therapy: how the disease changed in 14 years of observation in a tertiary referral center in Rome (Italy)

2021 ◽  
Author(s):  
Emanuela Del Giudice ◽  
Claudia Simio ◽  
Andrea Scala ◽  
Annalisa Di Coste ◽  
Giuseppe La Torre ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Biological Therapy ◽  
Ocular Complications ◽  
Tertiary Referral Center ◽  
The Past ◽  
Systemic Corticosteroids ◽  
Band Keratopathy ◽  
Current Therapies ◽  
Disease Modifying ◽  
Care Improvement

Abstract Objectives To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis. Methods Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy. Results 49 JIA patients analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort were on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying antirheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), elevated intraocular pressure (IOP) (p = 0.047) Conclusion. Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.

scholarly journals Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19

2021 ◽  
Vol 7 ◽  
Author(s):  
Xiao-Zhi Li ◽  
Yun Qiu ◽  
Louisa Jeffery ◽  
Fen Liu ◽  
Rui Feng ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Protein Expression ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Immunosuppressive Treatment ◽  
Before And After ◽  
Healthy Control ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Active Disease

Background and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients.Methods: We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed.Results: Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders (P &lt; 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate (P &lt; 0.0001) and mild (P = 0.0002) histologically active disease.Conclusion: Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD.

Comparative study of intracranial access in thrombectomy using next generation 0.088 inch guide catheter technology

2021 ◽  
pp. neurintsurg-2021-017341
Author(s):  
Devin V Bageac ◽  
Blake S Gershon ◽  
Jan Vargas ◽  
Maxim Mokin ◽  
Zeguang Ren ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Control Group ◽  
Anterior Circulation ◽  
Guide Catheter ◽  
Catheter Failure ◽  
Catheter Technology ◽  
Intracranial Vasculature

BackgroundMost conventional 0.088 inch guide catheters cannot safely navigate intracranial vasculature. The objective of this study is to evaluate the safety of stroke thrombectomy using a novel 0.088 inch guide catheter designed for intracranial navigation.MethodsThis is a multicenter retrospective study, which included patients over 18 years old who underwent thrombectomy for anterior circulation large vessel occlusions. Technical outcomes for patients treated using the TracStar Large Distal Platform (TracStar LDP) or earlier generation TRX LDP were compared with a matched cohort of patients treated with other commonly used guide catheters. The primary outcome measure was device-related complications. Secondary outcome measures included guide catheter failure and time between groin puncture and clot engagement.ResultsEach study arm included 45 patients. The TracStar group was non-inferior to the control group with regard to device-related complications (6.8% vs 8.9%), and the average time to clot engagement was 8.89 min shorter (14.29 vs 23.18 min; p=0.0017). There were no statistically significant differences with regard to other technical outcomes, including time to recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2B). The TracStar was successfully advanced into the intracranial internal carotid artery in 33 cases (73.33%); in three cases (6.67%), it was swapped for an alternate catheter. Successful reperfusion (mTICI 2B-3) was achieved in 95.56% of cases. Ninety-day follow-up data were available for 86.67% of patients, among whom 46.15% had an modified Rankin Score of 0–2%, and 10.26% were deceased.ConclusionsTracstar LDP is safe for use during stroke thrombectomy and was associated with decreased time to clot engagement. Intracranial access was regularly achieved.

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