AB0510 INFLIXIMAB IS AN EFFECTIVE GLUCOCORTICOID-SPARING TREATMENT FOR TAKAYASU ARTERITIS: RESULTS OF A MULTICENTER OPEN-LABEL PROSPECTIVE STUDY

Background:Approximately half of patients with Takayasu Arteritis (TA) have glucocorticoid (GC)-dependency and require the addition of a second-line immunosuppressive treatment.Objectives:Here, we conducted a multicenter open-label prospective cohort study to assess the efficacy and safety of infliximab originator as a GC-sparing agent in TA.Methods:A temporary recommendation for use for infliximab in refractory TA was approved by the French National Drug Authorities (April 2014). Infliximab was administered to patients in case of disease activity with a NIH score ≥2 despite conventional therapy. Data regarding patient’s clinical, laboratory, imaging and treatments were obtained at baseline, and at each following visit until last visit (October 2017). TA activity was evaluated according to NIH criteria and GC requirement throughout the study.Results:Twenty-three patients were enrolled, including 19 female. The median age at inclusion was 33 years (Interquartile range, IQR: 23-44 years). At baseline, 17 (74%) patients were treated with GCs, at a median dose of 10 mg/day (IQR: 0-21) of prednisone-equivalent. After a median follow-up of 36.9 months (IQR: 10-58.7), improvement of ≥1 NIH criterion of TA activity was achieved for 14/22 (64%) patients. The median GC dose was 8 mg/day (IQR: 7-10) at 6 months; 5 mg/day (IQR: 0-8) at 12 months and 0 mg/day (IQR: 0-5) at 36 months of follow-up. Overall, infliximab originator had a significant GC-sparing effect between baseline and last follow-up (p=0.009).Conclusion:This multicenter open-label cohort study suggests that infliximab originator is an effective GC-sparing treatment for TA refractory to conventional therapy.Disclosure of Interests:None declared

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Cohort study evaluating the impact of a discharge letter (DL) compared with usual care on adherence to surveillance following treatment for stage II/III colorectal cancer (CRC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.620 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 620-620 ◽

Cited By ~ 2

Author(s):

Janine Marie Davies ◽

Eugene Batuyong ◽

Sasha M. Lupichuk ◽

Robert Hilsden ◽

Misha Eliasziw ◽

...

Keyword(s):

Cohort Study ◽

Adjuvant Therapy ◽

Clinical Laboratory ◽

Ct Imaging ◽

Care Physician ◽

Stage Ii ◽

Disease Stage ◽

Cancer Centre ◽

The Impact

620 Background: The 2005 ASCO guidelines recommend surveillance testing and frequencies following surgical +/− adjuvant therapy for stage II/III CRC. In Canada, many patients are discharged from their oncologist to their primary care physician (PCP) for ongoing surveillance. However, adherence to surveillance recommendations is low. This cohort study evaluated adherence to surveillance 1 year after treatment of stage II/III CRC prior to and following implementation of a DL. Methods: Cohort 1 (C1) patients were retrospectively identified from the Alberta Cancer Registry following adjuvant therapy (as applicable) at a tertiary cancer centre (07/2006 - 09/2007). Cohort 2 (C2) patients were prospectively identified from the Registry and clinic records following adjuvant therapy (as applicable), as those discharged from the centre (10/2007 - 4/2009); DL was sent to the patient and PCP recommending surveillance tests and dates. Clinical, laboratory, diagnostic imaging, and endoscopy data was collated. Adherence at 1 year follow-up was compared between cohorts using Kaplan-Meier time-to-event analyses. Results: C1 (n=218) was larger than C2 (n=114) despite the longer accrual time for C2. There were no differences between cohorts by age, sex, primary site of disease, stage, or adjuvant oxaliplatin use. During year 1 of follow-up, 11.8% and 11.4% recurred (local or metastatic) and 6.5% and 2.7% died (p=0.1) in C1 and C2 respectively. Comparing C1 with C2, 14.8% vs. 23.0% of patients had one CEA test within 3 months, 45.2% vs. 72.2% within 6 months, and 71.7% vs. 85.1% within 1 year (p<0.001). Only 44.0% (C1) and 68.6% (C2) had 2 CEA tests within 1 year. Only 3.9% (C1) vs. 6.6% (C2) of patients had 4 CEA tests within the year following treatment as recommended. The rate of CT imaging was 32.3% (C1) and 56.1% (C2); endoscopy was 36.7% (C1) and 42.1% (C2). Conclusions: Implementation of a DL improved compliance with surveillance at 1 year of follow-up following discharge from a tertiary cancer centre, although optimal adherence remains low. However, adherence to CT imaging nearly doubled. Evaluation of compliance at 3 years of follow-up is ongoing.

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Tuberculous meningitis in adult patients of a Mexican neurological referral center: A-six-year retrospective cohort study

10.1101/2020.12.02.20242420 ◽

2020 ◽

Author(s):

Maldonado-Diaz Ellis Daniela ◽

Soto-Hernández José Luis ◽

Salinas-Lara Citlaltepetl ◽

Kammar-Garcia Ashuin ◽

Cárdenas Graciela

Keyword(s):

Cohort Study ◽

Tuberculous Meningitis ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Clinical Laboratory ◽

Hiv Positive ◽

Important Concern ◽

Lowenstein Jensen ◽

One Year

AbstractIntroductionTuberculosis (TB) remains as an important concern of public health worldwide because the high prevalence and severe sequelae. Tuberculous meningitis (TBM) is the most lethal and disabling form.AimTo describe the clinical, laboratory, and neuroimaging characteristics of TBM on admission at neurological center in Mexico City.MethodsRetrospective cohort study at the third level neurological center from 2010 to 2016. Clinical follow-up was evaluated at hospital discharge, three months, and one-year either due to lack of follow-up or mortality, during the follow-up the adverse events were registered.ResultsOne-hundred and six patients were included, 74 (69.8%) males and 32 (30.2%) females. From these 31 (29.2%) were HIV-positive. The median age was 35.5 (IQR:28-51). Pulmonary TB was found in 25% of the population. Alcoholism was observed in a half of the patients while diabetes in 15%, the latter being significant (p=0.04). Abnormalities in neuroimaging were significant among our population (p=0.003). Only one-third of the population had a positive Lowenstein-Jensen culture. There were no differences in clinical outcomes between HIV positive and non-HIV patients.ConclusionOur study shows data to those described in the literature. The initiation of empirical treatment in all patients with a high clinical suspicion of tuberculosis mandatory to try to avoid severe neurological sequels.

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POS0307 FATIGUE IN RHEUMATOID ARTHRITIS PATIENTS IS ASSOCIATED TO SUBJECTIVE BUT NOT OBJECTIVE ASSESSMENTS OF DISEASE ACTIVITY DURING TREATMENT WITH TOCILIZUMAB

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.152 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 379.1-380

Author(s):

H. B. Hammer ◽

B. Agular ◽

L. Terslev

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Joint Pain ◽

Patient Reported Outcomes ◽

Clinical Laboratory ◽

Inflammatory Activity ◽

Inadequate Response ◽

Open Label ◽

Patient Reported

Background:Fatigue is common in patients with rheumatoid arthritis (RA), and its association with inflammatory activity is not fully understood.Objectives:To explore the associations between fatigue and inflammation by clinical, laboratory and ultrasound examinations during follow-up of RA patients on biological treatment.Methods:A Nordic (Denmark, Finland, Norway, Sweden) open-label, single-arm study (part of the umbrella program – TOZURA (1)), enrolled patients with inadequate response to conventional synthetic (cs) DMARDs. Patients received tocilizumab 162 mg sc weekly for 24 weeks as monotherapy or in combination with a csDMARD. Stable oral NSAIDs and corticosteroids (≤10 mg/day prednisone or equivalent), were allowed. Patients were assessed at baseline, 4, 12 and 24 weeks for fatigue (FACIT-F questionnaire (total sum scores)), patient reported outcome measures ((PROMs) including joint pain and patient’s global visual analogue scale (VAS) as well as HAQ-DI), clinical assessments (tender and swollen joints, assessor’s global VAS), laboratory examinations (ESR, CRP) and ultrasound assessments (36 joints and 4 tendons, scored according to the Norwegian US atlas (2)). Spearman correlations, performed both at baseline and for changes from baseline of variables during follow-up, explored associations between fatigue and PROMs, clinical, laboratory as well as ultrasound variables. Predictive value of fatigue was investigated by linear regression.Results:110 patients were included (83% female, mean (SD) age 55.6 (12.1) years and RA duration 8.7 (9.5) years, 81% anti-CCP positive). All PROMs, clinical, laboratory and ultrasound variables decreased significantly, already after 4 weeks (p<0.001). Both for baseline assessments as well as for changes during follow-up, fatigue was associated with PROMs (Table 1 (baseline) and Table 2 (follow-up)). However, there were no or low associations between fatigue and clinical, laboratory and ultrasound assessments at baseline or during follow-up. In addition, baseline fatigue was predictive of joint pain, patient’s global VAS and HAQ-DI during follow-up (p<0.05-0.001), but not for the clinical, laboratory or ultrasound assessments.Conclusion:Fatigue assessed by an established questionnaire did not show any associations with several assessments of inflammatory activity in RA patients, neither at baseline nor during effective treatment. Thus, the present study adds to the increasing number of papers finding fatigue to reflect other aspects of RA disease activity than inflammation.References:[1]Choy E et al. Rheumatology 2018; 2. Hammer HB et al, ARD 2011Table 1.Spearman correlations between FACIT-F total score and patient reported outcomes, clinical, laboratory and ultrasound assessments. *p<0.05. **p<0.001Table 2.Spearman correlations between changes in FACIT-F total score from baseline to 4, 12 and 24 weeks and changes in patient reported outcomes, clinical, laboratory and ultrasound assessments. *p<0.05. **p<0.001Disclosure of Interests:Hilde Berner Hammer Speakers bureau: AbbVie, Pfizer, Roche, Lilly and Novartis, Consultant of: Novartis, Birte Agular Employee of: Roche, Lene Terslev Speakers bureau: Roche, MSD, BMS, Pfizer, AbbVie, Novartis and Janssen

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Different potencies of topical corticosteroids for a better treatment strategy in children with atopic dermatitis (the Rotterdam Eczema study): protocol for an observational cohort study with an embedded randomised open-label controlled trial

BMJ Open ◽

10.1136/bmjopen-2018-027239 ◽

2019 ◽

Vol 9 (6) ◽

pp. e027239

Author(s):

Karlijn F van Halewijn ◽

Arthur M Bohnen ◽

Pieter J van den Berg ◽

Suzanne G M A Pasmans ◽

Patrick J E Bindels ◽

...

Keyword(s):

Atopic Dermatitis ◽

Cohort Study ◽

Study Protocol ◽

Controlled Trial ◽

Observational Cohort Study ◽

Open Label ◽

Once Daily ◽

Stepwise Approach ◽

Observational Cohort

IntroductionTopical corticosteroids (TCS) of different potencies are the main treatment to control atopic dermatitis (AD). The Dutch guideline on AD for general practitioners (GPs) recommends a stepwise approach in which treatment steps are tailored to the severity of the disease, starting with the lowest possible potency of TCS. However, it remains unclear whether the recommended stepwise approach is most efficient. This randomised open-label controlled trial aims to determine whether a potent TCS is more effective than a low-potency TCS in the initial treatment of children with a moderate flare-up of AD in primary care. In the observational cohort, the overall aim is to determine the frequency, burden and determinants of flare-ups of AD during follow-up.Methods and analysisThe study is an observational cohort study with an embedded pragmatic randomised controlled, open-label trial. Eligible are patients diagnosed with AD (aged 12 weeks to 18 years) who visited the GP for AD or received repeated prescriptions for AD in the previous 12 months; follow-up of the cohort is 1 year. Children are enrolled in the trial if they have a flare-up of AD during follow-up in the cohort. Eligible children are randomised to the intervention group (with a potent TCS once daily) or to the GP guideline group (with a low potency TCS once daily). Primary outcome is the difference in average subjective disease severity over 24 weeks follow-up in the trial, measured with the patient-oriented eczema measure. As secondary outcome, the Eczema Area and Severity Index is measured.Ethics and disseminationThis study tests the hypothesis that immediate treatment with a potent TCS during a flare-up of AD leads to faster and more efficacious results as compared with starting with a TCS with low potency with less overall use of TCS. The study protocol is approved by the Medical Ethics Committee (MEC) of the Erasmus Medical Center Rotterdam, the Netherlands (MEC-2017–328). The results of the study will be published in international peer-reviewed journals and presented at national and international conferences.Trial registration numberNTR: 6679; Pre-results.

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P183 Assessing the safety of treatment cessation in Takayasu arteritis

Rheumatology ◽

10.1093/rheumatology/keaa111.178 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Chanaka Dahanayake ◽

Robert Maughan ◽

Taryn Youngstein ◽

Justin C Mason

Keyword(s):

Median Duration ◽

Takayasu Arteritis ◽

Inflammatory Markers ◽

Demographic Data ◽

Immunosuppressive Treatment ◽

Post Treatment ◽

Treatment Withdrawal ◽

Treatment Cessation ◽

Duration Of Treatment

Abstract Background Takayasu arteritis (TA) is a chronic granulomatous large vessel vasculitis. Patients typically receive immunosuppressive therapies, often continued indefinitely. Despite recent publication of recommendations for treatment initiation in TA, there is limited data on whether immunosuppressive treatments can ever be safely withdrawn. Our aim was to investigate the characteristics and outcomes of patients in long-term remission in whom immunosuppressive treatment had been stopped. Methods Clinical and radiographic data from a cohort of 160 TA patients followed-up over 20 years in a single tertiary specialist centre were analysed cross-sectionally, identifying those in whom immunosuppressive treatment was fully withdrawn. Baseline demographic data was collected and compared to those remaining on treatment. Outcomes assessed included status of follow-up imaging, change in inflammatory markers (CRP and ESR) and National Institute of Health (NIH) scores where data was available. A Mann Whitney U test was used for statistical analysis. Results Of the 160 patients analysed, 134 required treatment of whom 22 (16%) (all female, median age 47 years) had treatment fully withdrawn, after receiving immunosuppression for >6 months. Median age at diagnosis was 30 years and median number of arteries involved was 3. In those remaining on treatment, 89% were female (median age 47 years). All those withdrawn from treatment had received prednisolone, 15 methotrexate, 8 azathioprine, 2 mycophenolate and 2 cyclophosphamides. Median duration of treatment was 106 months (IQR 104 months). Median time from treatment cessation to analysis was 26 months (IQR 67 months). All 22 patients remained alive at the time of analysis, 17 (77%) had follow-up imaging post-treatment withdrawal (5 currently awaited). Only one patient suffered a disease flare after immunosuppression was stopped. This occurred 4 months post-withdrawal, confirmed by imaging with a positive FDG-PET scan, concurrent increases in inflammatory markers and NIH score consistent with new active disease. In the 21 cases in whom treatment was successfully withdrawn, CRP and ESR results pre- and post-treatment cessation were not significantly different (p = 0.944 and p = 0.322 respectively). Likewise, NIH scores compared pre- and post-treatment withdrawal revealed a median change 0 (range -1 to + 3). Conclusion Little data exists on the cessation of immunosuppression in complex rheumatic disease. Of 160 TA patients, 21/22 patients off treatment had stable outcomes. The baseline characteristics of this sub-group did not differ significantly from the whole cohort, however none of them had ever received biological therapy, suggesting a less refractory course. Although these data demonstrate that immunosuppression can be safely withdrawn, the median duration of treatment was 106 months, raising the question of whether withdrawal should be attempted earlier. Biomarkers are required to help identify those in whom treatment can be withdrawn. We aim to develop protocols to facilitate safe treatment cessation in order to minimise treatment-related side-effects and with potential economic impact. Disclosures C. Dahanayake None. R. Maughan None. T. Youngstein None. J.C. Mason Other; Professor Mason has participated in medical board meetings with Roche/Chugai.

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Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up

Journal of Clinical Medicine ◽

10.3390/jcm9103280 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3280

Author(s):

Manon Levy ◽

Juliette Abeillon ◽

Stéphane Dalle ◽

Souad Assaad ◽

Françoise Borson-Chazot ◽

...

Keyword(s):

Cell Death ◽

Cohort Study ◽

Programmed Cell Death ◽

Clinical Laboratory ◽

Morphological Characteristics ◽

University Hospital ◽

Acth Deficiency ◽

Programmed Cell Death 1

Hypophysitis, secondary to programmed cell death 1 protein (PD1) and programmed cell death 1 ligand 1 (PDL1) inhibitors, were thought to be rare, with only a few studies describing more than one case with long-term follow-up. The aim of the present study was to describe the clinical, laboratory, and morphological characteristics of PD1/PDL1 inhibitor-induced hypophysitis, and its long-term course. This cohort study was conducted at the University Hospital of Lyon, France, with longitudinal follow-up of patients. Seventeen cases of PD1/PDL1 inhibitor-induced hypophysitis were included. The median time to onset of hypophysitis was 28 weeks (range: 10–46). At diagnosis, 16 patients complained of fatigue, 12 of nausea or loss of appetite, while headache was rare. We found no imaging pituitary abnormality. All patients presented adrenocorticotropic hormone (ACTH) deficiency; other pituitary deficiencies were less common (n = 7). At last follow-up (median: 13 months), ACTH deficiency persisted in all but one patient and one patient recovered from gonadotropic deficiency. PD1/PDL1 inhibitor-induced hypophysitis is a clinical entity different from those associated to cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors, with less obvious clinical and radiological signs, and probably a different mechanism. The paucity of symptoms demonstrates the need for systematic hormonal follow-up for patients receiving PD1/PDL1 inhibitors.

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