The clinical perspective: How to personalise treatment in MS and how may biomarkers including imaging contribute to this?

Background: Multiple sclerosis (MS) is a highly heterogeneous disease, both in its course and in its response to treatments. Effective biomarkers may help predict disability progression and monitor patients’ treatment responses. Objective: The aim of this review was to focus on how biomarkers may contribute to treatment individualisation in MS patients. Methods: This review reflects the content of presentations, polling results and discussions on the clinical perspective of MS during the first and second Pan-European MS Multi-stakeholder Colloquia in Brussels in May 2014 and 2015. Results: In clinical practice, magnetic resonance imaging (MRI) measures play a significant role in the diagnosis and follow-up of MS patients. Together with clinical markers, the rate of MRI-visible lesion accrual once a patient has started treatment may also help to predict subsequent treatment responsiveness. In addition, several molecular (immunological, genetic) biomarkers have been established that may play a role in predictive models of MS relapses and progression. To reach personalised treatment decisions, estimates of disability progression and likely treatment response should be carefully considered alongside the risk of serious adverse events, together with the patient’s treatment expectations. Conclusion: Although biomarkers may be very useful for individualised decision making in MS, many are still research tools and need to be validated before implementation in clinical practice.

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AB0249 SAFETY OF BARICITINIB IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS (RA): THE 2020 INTERIM REPORT FROM ALL-CASE POST MARKETING SURVEILLANCE IN CLINICAL PRACTICE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.433 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1150.1-1150

Author(s):

T. Fujii ◽

T. Atsumi ◽

N. Okamoto ◽

N. Takahashi ◽

N. Tamura ◽

...

Keyword(s):

Clinical Practice ◽

Adverse Events ◽

Aspiration Pneumonia ◽

Japanese Patients ◽

Research Support ◽

Serious Adverse Events ◽

Chugai Pharmaceutical ◽

Post Marketing Surveillance ◽

Otsuka Pharmaceutical ◽

Post Marketing

Background:An all-case post marketing surveillance (PMS) of baricitinib (Bari), that started in Sep 2017, collects safety and effectiveness for the first 24 wks of treatment and continues to collect serious adverse events (SAEs) for 3 yrs.Objectives:To evaluate Bari safety in RA patients (pt) in clinical practice.Methods:We report pt baseline demographics and adverse events (AEs) up to 24 wks for pts whose case report files for 24-wk data were completed as of Jun 2020.Results:Data from 3445 pts were analyzed (females=80%, mean age=64yr, mean RA duration 12yr). Bari dose regimen was as follows: 4mg, 60%, 2mg, 27%, 4mg→2mg, 5%, 2mg→4mg, 5%, and others, 2%. Concomitant use of MTX and glucocorticoid was 65% and 48%, respectively. 74% continued treatment for 24 wks. AE and SAE were recognized in 887 (26%) and 122 pts (4%), respectively. 6 pts died of pneumonia, aspiration pneumonia, bacterial pneumonia, cerebral infarction/ILD/aspiration pneumonia, adenocarcinoma, and colorectal cancer. Major AEs were as follows: herpes zoster=3%, liver dysfunction=3%, serious infection=1%, anemia=1%, hyperlipidemia=1%, malignancy=0.3%, interstitial pneumonia=0.2%, MACE=0.1%, and VTE=0.1%.Conclusion:Data do not show new safety concerns and encourage guideline-compliant use of Bari.Disclosure of Interests:Takao Fujii Speakers bureau: Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; Ono Pharmaceutical Co. Ltd., Consultant of: Asahikasei Pharma Corp, Grant/research support from: Asahikasei Pharma Corp; AbbVie Japan GK; Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Ono Pharmaceutical Co., Ltd., Tatsuya Atsumi Speakers bureau: AbbVie Japan GK; Astellas Pharma Inc.; Bristol-Myers Squibb Co. Ltd; Chugai Pharmaceutical Co. Ltd.; Daiichi Sankyo Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., UCB Japan Co. Ltd., Consultant of: AbbVie Japan GK; AstraZeneca plc.; Boehringer Ingelheim Co. Ltd.; Medical & Biological Laboratories Co. Ltd.; Novartis Pharma K.K.; Ono Pharmaceutical Co. Ltd.; Pfizer Japan Inc., Grant/research support from: Astellas Pharma Inc., Alexion Inc.; Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co., Ltd.Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., Nami Okamoto Speakers bureau: AbbVie Japan GK; Asahikasei Pharma Co.; AYUMI Pharmaceutical Co.Eisai Co. Ltd; Bristol-Myers Squibb Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Pfizer Japan Inc.Sanofi K.K.; Chugai Pharmaceutical Co. Ltd.; Novartis Pharma Co.; Teijin Pharma Ltd.; Torii Pharmaceutical Co., Ltd., Nobunori Takahashi Speakers bureau: AbbVie Japan GK; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Chugai Pharmaceutical Co., Ltd.; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; UCB Japan Co. Ltd.; Astellas Pharma Inc.; Bristol Myers Squibb Co. Ltd., Grant/research support from: Bristol Myers Squibb Co. Ltd., Naoto Tamura Speakers bureau: AbbVie Japan GK; Bristol Myers Squibb Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Glaxo Smith Kline K.K.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co., Atsuo Nakajima: None declared, Ayako Nakajima Speakers bureau: AbbVie Japan GK; Actelion Pharmaceuticals Japan Ltd., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd.,Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Glaxo Smith Kline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Teijin Pharma Ltd., Grant/research support from: Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Hiroaki Matsuno Speakers bureau: Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Consultant of: Mochida Pharmaceutical Co., Ltd., Grant/research support from: Astellas Pharma Inc., Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K, Naoto Tsujimoto Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Atsushi Nishikawa Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Taeko Ishii Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Masataka Kuwana Speakers bureau: AbbVie Japan GK, Astellas Pharma Inc., Asahi Kasei Pharma Co., Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Medical &Biological Laboratories Co., Ltd.; Mitsubishi Tanabe Pharma Co.; Mochida Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Pfizer Japan Inc., Consultant of: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Corbus Pharmaceuticals Holdings, Inc.; Medical &Biological Laboratories Co., Ltd.; Mochida Pharmaceutical Co., Ltd., Grant/research support from: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Medical &Biological Laboratories Co., Ltd; Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., Ltd., Michiaki Takagi Speakers bureau: Yes, but sponsored lectures without COI in the academic meetings, only.

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Repurposing Domperidone in Secondary Progressive MS

Neurology ◽

10.1212/wnl.0000000000011863 ◽

2021 ◽

pp. 10.1212/WNL.0000000000011863

Author(s):

Marcus W. Koch ◽

Kayla Sage ◽

Sharanjit Kaur ◽

Janet Kim ◽

Graziela Cerchiaro ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Phase 2 ◽

Disability Progression ◽

Two Stage ◽

Serious Adverse Events ◽

Secondary Progressive ◽

Link Type

ObjectiveTo assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon two-stage design.MethodsWe enrolled patients in an open-label, Simon two-stage, single-center, phase 2, single-arm futility trial at the Calgary MS Clinic if they met the following criteria: age 18–60 years, SPMS, screening EDSS score of 4.0–6.5 and screening T25FW of 9 seconds or more. Patients received domperidone 10 mg QID for one year. The primary outcome was worsening of disability, defined as worsening of the T25FW performance by 20% or more at 12 months compared to at baseline. This trial is registered with ClinicalTrials.gov, number NCT02308137.ResultsBetween February 13, 2015 and January 3, 2020, 110 patients were screened, 81 received treatment, 64 completed follow-up, of whom 62 were analysed. The study did not meet its primary endpoint: 22 of 62 (35%) patients experienced significant worsening of disability, which is close to the expected proportion of 40%, and above the pre-defined futility threshold. Patients with higher prolactin levels during the study had a significantly lower risk of disability progression, which may warrant further investigation. Domperidone treatment was reasonably well tolerated, but adverse events occurred in 84% and serious adverse events in 15% of patients.ConclusionsDomperidone treatment could not reject futility in reducing disability progression in SPMS. The Simon two-stage trial model may be a useful model for phase 2 studies in progressive MS.Classification of evidenceThis study provides Class III evidence that in individuals with secondary progressive multiple sclerosis participating in a futility trial, domperidone treatment could not reject futility in reducing disability progression at 12 months.

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Should We Use Clinical Tools to Identify Disease Progression?

Frontiers in Neurology ◽

10.3389/fneur.2020.628542 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hernan Inojosa ◽

Undine Proschmann ◽

Katja Akgün ◽

Tjalf Ziemssen

Keyword(s):

Multiple Sclerosis ◽

Clinical Markers ◽

Disability Progression ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Secondary Progressive ◽

Disability Status ◽

Relapsing Remitting ◽

Clinical Tools

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted. The characterization of structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed to differentiate between both phenotypes. However, there is no definite threshold between them. Whether the risk of clinical progression can be predicted by structural markers at early disease phases is still a focus of clinical research. However, several theories and pathological evidence suggest that both disease phenotypes are part of a continuum with common pathophysiological mechanisms. In this case, the clinical evaluation of the patients would play a preponderant role above destruction biomarkers for the early identification of disability progression and SPMS. For this purpose, the use of clinical tools beyond the Expanded Disability Status Scale (EDSS) should be considered. Besides established functional tests such as the Multiple Sclerosis Functional Composite (MSFC), patient's neurological history or digital resources may help neurologists in the decision-taking. In this article, we discuss arguments for the use of clinical markers in the detection of secondary progressive MS and the characterization of progressive disease activity.

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Individual Expectation: An Overlooked, but Pertinent, Factor in the Treatment of Individuals Experiencing Musculoskeletal Pain

Physical Therapy ◽

10.2522/ptj.20090306 ◽

2010 ◽

Vol 90 (9) ◽

pp. 1345-1355 ◽

Cited By ~ 95

Author(s):

Joel E. Bialosky ◽

Mark D. Bishop ◽

Joshua A. Cleland

Keyword(s):

Clinical Practice ◽

Clinical Outcomes ◽

Musculoskeletal Pain ◽

Current Literature ◽

Potential Role ◽

Physical Therapists ◽

Clinical Perspective ◽

The Relationship

Physical therapists consider many factors in the treatment of patients with musculoskeletal pain. The current literature suggests expectation is an influential component of clinical outcomes related to musculoskeletal pain for which physical therapists frequently do not account. The purpose of this clinical perspective is to highlight the potential role of expectation in the clinical outcomes associated with the rehabilitation of individuals experiencing musculoskeletal pain. The discussion focuses on the definition and measurement of expectation, the relationship between expectation and outcomes related to musculoskeletal pain conditions, the mechanisms through which expectation may alter musculoskeletal pain conditions, and suggested ways in which clinicians may integrate the current literature regarding expectation into clinical practice.

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P521Conversion test during Subcutaneous Implantable Cardioverter-Defibrillator Implantation in clinical practice: in-hospital and mid-term outcome

EP Europace ◽

10.1093/europace/euaa162.118 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

V Bianchi ◽

I Diemberger ◽

V Tavoletta ◽

L Perrotta ◽

L Ottaviano ◽

...

Keyword(s):

Clinical Practice ◽

Ejection Fraction ◽

Systolic Function ◽

Implantable Cardioverter Defibrillators ◽

Icd Implantation ◽

Serious Adverse Events ◽

Term Outcome ◽

Appropriate Shocks ◽

Ct Data

Abstract Funding Acknowledgements No funding OnBehalf RHYTHM DETECT Registry Background With subcutaneous implantable cardioverter–defibrillators (S-ICD), conversion test (CT) is still recommended at implantation. However, prior works found that adherence to this recommendation is declining in clinical practice. Purpose To describe current practice regarding CT at S-ICD implantation, and also measure in-hospital outcome of patients who underwent CT and mid-term outcome of patients without CT. Methods We analyzed 1652 consecutive patients (49 ± 15 years old, 80% male, 51% with ischemic or non-ischemic dilated cardiomyopathy, 45% with ejection fraction ≤35%) who underwent S-ICD implantation in 60 Italian centers from 2013 to 2019. Results CT data were missing in 27 patients. CT was performed in 1300 patients. Successful conversion with ≤65J was obtained in 97.4% of patients. Shock at 80J was not effective in 12 (0.9%) patients. In 10 of these patients the CT was successful after device repositioning, while in 2 patients it was decided to implant a transvenous ICD. Two (0.15%) episodes of electromechanical dissociation (1 fatal) were reported as consequence of CT. CT was not performed in 325 patients (for clinical reasons in 182 patients, for facility preference in 71, ventricular fibrillation not inducible in 72 patients). As compared to the CT group, these patients were older (51 ± 16 vs. 48 ± 15 years; p < 0.01) and had lower ejection fraction (37 ± 16% vs. 46 ± 16%; p < 0.01). 243 non-CT patients had at least 6 months follow-up (median 15 months). In this group, 12 (4.9%) patients had appropriate shocks to treat VT/VF (all successfully terminated with the first shock), and 9 (3.7%) patients had inappropriate shocks. Conclusions This analysis showed that CT is frequently omitted in current clinical practice, especially in older patients with worse systolic function. Shocks at CT are very frequently effective and system revision after CT is rarely required. CT is also safe, although serious adverse events cannot be excluded. A strategy that omits CT did not appear to compromise the effectiveness of the S-ICD, but larger populations and longer follow-up are needed to confirm this finding.

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High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice

Multiple Sclerosis Journal ◽

10.1177/1352458519894713 ◽

2019 ◽

Vol 26 (14) ◽

pp. 1898-1906 ◽

Cited By ~ 2

Author(s):

Laura Couloume ◽

Laetitia Barbin ◽

Emmanuelle Leray ◽

Sandrine Wiertlewski ◽

Emmanuelle Le Page ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Practice ◽

Prospective Study ◽

Outcome Measures ◽

Progressive Multiple Sclerosis ◽

Routine Clinical Practice ◽

High Dose ◽

Disability Progression ◽

Edss Score ◽

Multiple Sclerosis Patients

Background: A recent controlled trial suggested that high-dose biotin supplementation reverses disability progression in patients with progressive multiple sclerosis. Objective: To analyze the impact of high-dose biotin in routine clinical practice on disability progression at 12 months. Methods: Progressive multiple sclerosis patients who started high-dose biotin at Nantes or Rennes Hospital between 3 June 2015 and 15 September 2017 were included in this prospective study. Disability outcome measures, patient-reported outcome measures, relapses, magnetic resonance imaging (MRI) data, and adverse events were collected at baseline, 6, and 12 months. Results: A total of 178 patients were included. At baseline, patients were 52.0 ± 9.4 years old, mean Expanded Disability Status Scale (EDSS) score was 6.1 ± 1.3, mean disease duration was 16.9 ± 9.5 years. At 12 months, 3.8% of the patients had an improved EDSS score. Regarding the other disability scales, scores either remained stable or increased significantly. In total, 47.4% of the patients described stability, 27.6% felt an improvement, and 25% described a worsening. Four patients (2.2%) had a relapse. Of the 74 patients (41.6%) who underwent an MRI, 20 (27.0%) had new T2 lesions, 8 (10.8%) had gadolinium-enhancing lesions. Twenty-five (14%) reported adverse event. Conclusion: In this study, high-dose biotin did not seem to be associated with a clear improvement in disability.

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Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group

Arthritis Research & Therapy ◽

10.1186/s13075-020-02313-w ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Irini Genitsaridi ◽

Irini Flouri ◽

Dimitris Plexousakis ◽

Konstantinos Marias ◽

Kyriaki Boki ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Serious Adverse Events ◽

Term Outcome ◽

Mixed Effect ◽

Long Term Outcome ◽

Moderate Disease ◽

Moderate Disease Activity

Abstract Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups. Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

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Statins and age: is there a limit beyond which primary prevention is futile?

European Heart Journal Supplements ◽

10.1093/eurheartj/suab103 ◽

2021 ◽

Vol 23 (Supplement_E) ◽

pp. E109-E111

Author(s):

Gian Piero Perna

Keyword(s):

Clinical Practice ◽

Side Effects ◽

Primary Prevention ◽

Subclinical Atherosclerosis ◽

Lipid Lowering ◽

Clinical Markers ◽

Vascular Events ◽

Increased Risk ◽

Glomerular Filtrate ◽

Meta Analyses

Abstract Hypercholesterolaemic patients at an advanced age (>75 years) with and without known cardiovascular disease are at higher cardiovascular risk than younger subjects, and the frequency of vascular events in this group of the patient increases with increasing age. However, in clinical practice, these subjects are undertreated for various reasons: conservative cultural attitude, fear of side effects, doubts about efficacy, lack of specific trials. Two recent meta-analyses have shown that the use of lipid-lowering drugs is as safe and effective in this age group as in younger subjects. Subjects aged >75 years in primary prevention are poorly represented in trials but should be considered for treatment in daily clinical practice, because, in the risk assessment (SCORE algorithm), they are very often classified as intermediate or high risk but can also be reclassified at increased risk if an additional assessment step with clinical markers (diabetes and reduced glomerular filtrate) or cardiovascular imaging is used for the detection of subclinical atherosclerosis. Greater attention to treatment methods and monitoring of possible side effects is recommended, but the only limit to the treatment is its ‘futility’ in the fragile patient.

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Immuno-related endocrinopathy in patients treated with immune checkpoint inhibitors

Medical Council ◽

10.21518/2079-701x-2020-9-16-24 ◽

2020 ◽

pp. 16-24

Author(s):

D. I. Yudin ◽

K. K. Laktionov ◽

K. A. Sarantseva ◽

O. I. Borisova ◽

V. V. Breder ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Clinical Practice ◽

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Serious Adverse Events ◽

Immune Mediated ◽

Discontinuation Of Treatment ◽

The Russian Federation

Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.

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Real-world experience of fingolimod in patients with multiple sclerosis (MS Fine): An observational study in the UK

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318801638 ◽

2018 ◽

Vol 4 (4) ◽

pp. 205521731880163

Author(s):

Gordon Mazibrada ◽

Charlotte Sharples ◽

Ines Perfect

Keyword(s):

Multiple Sclerosis ◽

Clinical Practice ◽

Observational Study ◽

Disease Activity ◽

Relapse Rate ◽

Disability Progression ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

The Uk ◽

Relapsing Remitting Multiple Sclerosis

Background Fingolimod is approved for the treatment of highly active relapsing–remitting multiple sclerosis in Europe. There is limited information on its effectiveness and safety in clinical practice within the UK. Objective To evaluate retrospectively the effectiveness and safety of fingolimod in patients with relapsing–remitting multiple sclerosis who were prescribed fingolimod by UK neurologists within the National Health Service. Methods This was a multicentre, observational study conducted in the UK. Patients were initiated on fingolimod 0.5 mg 12 months before inclusion in the study. Key efficacy outcomes included annualised relapse rate and the proportion of patients free from relapses, disability progression and clinical and radiological disease activity at 12 months following fingolimod initiation. Resource utilisation and safety outcomes were also assessed. Results In 12 months of treatment with fingolimod, the mean annualised relapse rate was reduced by 79%, the majority of patients were free from relapses (83.7%). Based on limited data, most patients were free from disability progression and clinical and radiological disease activity. More than 90% of patients continued on fingolimod. Lymphocyte count reductions and liver enzyme increases were observed. Conclusion Fingolimod was effective in reducing the disease activity in relapsing–remitting multiple sclerosis patients requiring an escalation from first-line therapies who were prescribed fingolimod in clinical practice in the UK.

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