Susana Ferreira, autor em New Breathe

Susana Ferreira

21/Dec/2021

Acute Myeloid Leukemia Case after Gene Therapy for Sickle Cell Disease

Gene therapy with LentiGlobin for sickle cell disease (bb1111, lovotibeglogene autotemcel) consists of autologous transplantation of a patient’s hematopoietic stem cells transduced with the BB305 lentiviral vector that encodes the βA-T87Q-globin gene. Acute myeloid leukemia developed in a woman approximately 5.5 years after she had received LentiGlobin for sickle cell disease as part of the initial cohort (Group A) of the HGB-206 study. An analysis of peripheral-blood samples revealed that blast cells contained a BB305 lentiviral vector insertion site. The results of an investigation of causality indicated that the leukemia was unlikely to be related to vector insertion, given the location of the insertion site, the very low transgene expression in blast cells, and the lack of an effect on expression of surrounding genes. Several somatic mutations predisposing to acute myeloid leukemia were present after diagnosis, which suggests that patients with sickle cell disease are at increased risk for hematologic malignant conditions after transplantation, most likely because of a combination of risks associated with underlying sickle cell disease, transplantation procedure, and inadequate disease control after treatment. (Funded by Bluebird Bio.)

Sunita Goyal, M.D., John Tisdale, M.D., Manfred Schmidt, Ph.D., Julie Kanter, M.D., Jennifer Jaroscak, M.D., Dustin Whitney, Ph.D., Hans Bitter, Ph.D., Philip D. Gregory, Ph.D., Geoffrey Parsons, Ph.D., Marianna Foos, M.S., Ashish Yeri, Ph.D., Maple Gioia, A.L.M., et al.

This article was published on December 12, 2021, at NEJM.org.

Leukemia

Susana Ferreira

14/Dec/2021

Efficacy and safety of carboplatin with nab-paclitaxel versus docetaxel in older patients with squamous non-small-cell lung cancer (CAPITAL): a randomised, multicentre, open-label, phase 3 trial

Background
In Japan, docetaxel, a cytotoxic monotherapy, is the standard drug administered to older patients with advanced non-small-cell lung cancer (NSCLC). Carboplatin plus nab-paclitaxel has shown a high objective response rate in patients with squamous histology and was suggested to improve overall survival in patients aged 70 years and older. The CAPITAL trial aimed to assess the safety and efficacy of carboplatin plus nab-paclitaxel versus docetaxel as first-line therapy for patients aged 70 years and older with advanced squamous NSCLC.

Methods
This multicentre, open-label, randomised, phase 3 trial was carried out at 92 medical institutions in Japan. Eligible patients were aged 70 years and older, had advanced squamous NSCLC with no previous systemic chemotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Using an electronic data capture system, patients were randomly assigned (1:1) to intravenous carboplatin (area under the concentration-time curve of 6 mg/mL per min for 30 min) on day 1 of a 21-day cycle and intravenous nab-paclitaxel (100 mg/m2 for 60 min) on days 1, 8, and 15 every 3 weeks or intravenous docetaxel (60 mg/m2 for 60 min) on day 1 every 3 weeks. Randomisation was computer-generated per participant and stratified by ECOG performance status, clinical stage, sex, age, and institution. The primary endpoint was overall survival, measured in the full analysis set and defined as the time from registration to the date of death due to any cause. Safety was assessed in all patients who received at least one dose of the trial treatment. This trial is registered with the UMIN Clinical Trials Registry, UMIN000019843, and the Japan Registry of Clinical Trials, jRCTs041180110. After the planned interim analysis in Aug 3, 2020, the independent data monitoring committee recommended that the trial be stopped early. This report represents the final analysis.

Findings
Between Feb 24, 2016, and Aug 11, 2020, 196 patients were enrolled and were randomly assigned to the carboplatin plus nab-paclitaxel group (n=98) or the docetaxel group (n=98). Of these patients, four (carboplatin plus nab-paclitaxel group, n=3; docetaxel group, n=1) did not receive any treatment and two patients in the docetaxel group were excluded from the full analysis set. Median overall survival in the full analysis set was 16·9 months (95% CI 12·6–25·4) in the carboplatin plus nab-paclitaxel group and 10·9 months (8·5–12·4) in the docetaxel group (hazard ratio 0·52 [90% CI 0·38–0·70]; p=0·0003). Grade 3–4 adverse events occurred in 79 (83%) patients in the carboplatin plus nab-paclitaxel group and 77 (79%) patients in the docetaxel group (p=0·63). The most common grade 3–4 adverse events in the carboplatin plus nab-paclitaxel group and the docetaxel group were leukopenia (44 [46%] vs 55 [57%]; p=0·20), neutropenia (60 [63%] vs 75 [77%]; p=0·046), febrile neutropenia (nine [10%] vs 19 [20%]; p=0·073), and anaemia (37 [39%] vs two [2%]; p<0·0001). Serious treatment-related adverse events of all grades occurred in 13 (14%) patients in the carboplatin plus nab-paclitaxel group and 11 (11%) patients in the docetaxel group. Treatment-related deaths occurred in two (2%; respiratory failure n=1, visceral arterial ischaemia n=1) patients in the carboplatin plus nab-paclitaxel group and one (1%; sepsis) patient in the docetaxel group.

Interpretation
Our study showed that overall survival was longer with carboplatin plus nab-paclitaxel than with docetaxel, suggesting that carboplatin plus nab-paclitaxel can be used as standard first-line treatment for patients aged 70 years and older with advanced squamous NSCLC.

Yoshihito Kogure, MD; Shunichiro Iwasawa, MD; Hideo Saka, MD; Yoichiro Hamamoto, MD; Akiko Kada, MPH; Hiroya Hashimoto, PhD; et al.

Lung cancer

Susana Ferreira

09/Nov/2021

Biliary tract cancer

Biliary tract cancers, including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are low-incidence malignancies in most high-income countries, but represent a major health problem in endemic areas; moreover, the incidence of intrahepatic cholangiocarcinoma is rising globally. Surgery is the cornerstone of cure; the optimal approach depends on the anatomical site of the primary tumour and the best outcomes are achieved through management by specialist multidisciplinary teams. Unfortunately, most patients present with locally advanced or metastatic disease. Most studies in advanced disease have pooled the various subtypes of biliary tract cancer by necessity to achieve adequate sample sizes; however, differences in epidemiology, clinical presentation, natural history, surgical therapy, response to treatment, and prognosis have long been recognised. Additionally, the identification of distinct patient subgroups harbouring unique molecular alterations with corresponding targeted therapies (such as isocitrate dehydrogenase-1 mutations and fibroblast growth factor receptor-2 fusions in intrahepatic cholangiocarcinoma, among others) is changing the treatment paradigm. In this Seminar we present an update of the causes, diagnosis, molecular classification, and treatment of biliary tract cancer.

Prof Juan W Valle, MD; R Katie Kelley, MD; Bruno Nervi, MD; Prof Do-Youn Oh, PhD; Prof Andrew X Zhu, MD

Susana Ferreira

02/Nov/2021

Alzheimer’s disease

In this Seminar, we highlight the main developments in the field of Alzheimer’s disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer’s disease. The earliest phase of Alzheimer’s disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer’s disease is 60–80% dependent on heritable factors, with more than 40 Alzheimer’s disease-associated genetic risk loci already identified, of which the APOE alleles have the strongest association with the disease. Novel biomarkers include PET scans and plasma assays for amyloid β and phosphorylated tau, which show great promise for clinical and research use. Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia. Lifestyle factors do not directly affect Alzheimer’s disease pathology, but can still contribute to a positive outcome in individuals with Alzheimer’s disease. Promising pharmacological treatments are poised at advanced stages of clinical trials and include anti-amyloid β, anti-tau, and anti-inflammatory strategies.

Prof Philip Scheltens, MD; Prof Bart De Strooper, MD; Prof Miia Kivipelto, MD, Henne Holstege, PhD; Prof Gael Chételat, MD; Prof Charlotte E Teunissen, PhD

Alzheimer’s disease

Susana Ferreira

26/Oct/2021

Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia

Hairy-cell leukemia (HCL) is a CD20+ indolent B-cell cancer in which a BRAF V600E kinase–activating mutation plays a pathogenetic role. In clinical trials involving patients with refractory or relapsed HCL, the targeting of BRAF V600E with the oral BRAF inhibitor vemurafenib led to a response in 91% of the patients; 35% of the patients had a complete response. However, the median relapse-free survival was only 9 months after treatment was stopped.

Methods

In a phase 2, single-center, academic trial involving patients with refractory or relapsed HCL, we assessed the safety and efficacy of vemurafenib (960 mg, administered twice daily for 8 weeks) plus concurrent and sequential rituximab (375 mg per square meter of body-surface area, administered for 8 doses over a period of 18 weeks). The primary end point was a complete response at the end of planned treatment.

Results

Among the 30 enrolled patients with HCL, the median number of previous therapies was 3. A complete response was observed in 26 patients (87%) in the intention-to-treat population. All the patients who had HCL that had been refractory to chemotherapy (10 patients) or rituximab (5) and all those who had previously been treated with BRAF inhibitors (7) had a complete response. Thrombocytopenia resolved after a median of 2 weeks, and neutropenia after a median of 4 weeks. Of the 26 patients with a complete response, 17 (65%) were cleared of minimal residual disease (MRD). Progression-free survival among all 30 patients was 78% at a median follow-up of 37 months; relapse-free survival among the 26 patients with a response was 85% at a median follow-up of 34 months. In post hoc analyses, MRD negativity and no previous BRAF inhibitor treatment correlated with longer relapse-free survival. Toxic effects, mostly of grade 1 or 2, were those that had previously been noted for these agents.

Conclusions

In this small study, a short, chemotherapy-free, nonmyelotoxic regimen of vemurafenib plus rituximab was associated with a durable complete response in most patients with refractory or relapsed HCL.

Enrico Tiacci, M.D., Luca De Carolis, M.D., Edoardo Simonetti, M.D., Monia Capponi, M.D., Achille Ambrosetti, M.D., Eugenio Lucia, M.D., Agostino Antolino, M.D., Alessandro Pulsoni, M.D., Samantha Ferrari, M.D., Pier L. Zinzani, M.D., Stefano Ascani, M.D., Vincenzo M. Perriello, M.D., et al.

Leukemia

Susana Ferreira

19/Oct/2021

Lung Cancer

We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%.

Methods

In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0–1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing.

Findings

Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17·9–not evaluable) with cemiplimab (n=283) versus 14·2 months (11·2–17·5) with chemotherapy (n=280; hazard ratio [HR] 0·57 [0·42–0·77]; p=0·0002). Median progression-free survival was 8·2 months (6·1–8·8) with cemiplimab versus 5·7 months (4·5–6·2) with chemotherapy (HR 0·54 [0·43–0·68]; p<0·0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3–4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy.

Interpretation

Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population.

Funding

Regeneron Pharmaceuticals and Sanofi.

Ahmet Sezer, MD; Prof Saadettin Kilickap, MD; Prof Mahmut Gümüş, MD; Prof Igor Bondarenko, MD; Prof Mustafa Özgüroğlu, MD; Miranda Gogishvili, MD; et al.

Lung cancer

Susana Ferreira

12/Oct/2021

Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial

HER2 amplification has been identified in 2–3% of patients with colorectal cancer, although there are currently no approved HER2-targeted therapies for colorectal cancer. We aimed to study the antitumour activity and safety of trastuzumab deruxtecan (an antibody–drug conjugate of humanised anti-HER2 antibody with topoisomerase I inhibitor payloads) in patients with HER2-expressing metastatic colorectal cancer.

Methods

DESTINY-CRC01 is an open-label, phase 2 study that recruited patients from 25 clinics and hospitals in Italy, Japan, Spain, the UK, and the USA. Eligible patients had centrally confirmed HER2-expressing metastatic colorectal cancer that had progressed on two or more previous regimens (HER2-targeted therapies other than trastuzumab deruxtecan permitted), were aged 18 years or older (≥20 years in Japan), had an Eastern Cooperative Oncology Group score of 0 or 1, and had RAS and BRAFV600E wild-type tumours. Patients were enrolled into one of three cohorts by HER2 expression level: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC2+ and in-situ hybridisation [ISH]-positive), cohort B (IHC2+ and ISH-negative), or cohort C (IHC1+). Patients received 6·4 mg/kg trastuzumab deruxtecan intravenously every 3 weeks until disease progression, unacceptable adverse events, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate in cohort A by independent central review which was assessed in the full analysis set and safety was assessed in the safety analysis set. Both the full analysis set and the safety analysis set included all patients who received one or more doses of trastuzumab deruxtecan. This ongoing trial is registered with ClinicalTrials.gov, number NCT03384940.

Findings

Between Feb 23, 2018, and July 3, 2019, 78 patients were enrolled in the study (53 in cohort A, seven in cohort B, and 18 in cohort C), all of whom received at least one dose of study drug. For the 53 (68%) patients with HER2-positive tumours (cohort A), a confirmed objective response was reported in 24 (45·3%, 95% CI 31·6–59·6) patients after a median follow-up of 27·1 weeks (IQR 19·3–40·1). Grade 3 or worse treatment-emergent adverse events that occurred in at least 10% of all participants were decreased neutrophil count (17 [22%] of 78) and anaemia (11 [14%]). Five patients (6%) had adjudicated interstitial lung disease or pneumonitis (two grade 2; one grade 3; two grade 5, the only treatment-related deaths).

Interpretation

Trastuzumab deruxtecan showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with that reported in previous trastuzumab deruxtecan trials. Interstitial lung disease and pneumonitis are important risks requiring careful monitoring and prompt intervention.

Salvatore Siena, Maria Di Bartolomeo, Kanwal Raghav, Toshiki Masuishi, Fotios Loupakis, Hisato Kawakami, Kensei Yamaguchi, Tomohiro Nishina, Marwan Fakih, Elena Elez, Javier Rodriguez, Fortunato Ciardiello, Yoshito Komatsu, Taito Esaki, Ki Chung, Zev Wainberg, Andrea Sartore-Bianchi, Kapil Saxena, Eriko Yamamoto, Emarjola Bako, Yasuyuki Okuda, Javad Shahidi, Axel Grothey, Takayuki Yoshino, on behalf of the DESTINY-CRC01 investigators

Colorectal Cancer

Susana Ferreira

28/Sep/2021

Clinical Trials

Clinical trials are studies conducted in humans designed to discover or verify the effects of one or more investigational drugs. These are essential for confirming the safety and efficacy of new drugs, as well as for testing new uses of drugs already on the market. Those responsible for planning and conducting a clinical trial must carefully assess whether the potential benefits resulting from the participation of patients in a particular clinical trial outweigh any risks that the research may involve, as clinical trials involve ethical issues and some risks and their impact on the patients involved must be carefully evaluated.

Clinical trials are always considered the best treatment, as it results from the use of the best drugs with the best technology and even the best treatment available for this condition. Those who participate may or may not benefit from the treatment, however they will always have the support, comfort, monitoring and follow-up of an experienced and qualified research team.
Although there is always the chance that a new treatment will prove ineffective, the results obtained at earlier stages of the development of a new treatment make researchers believe that they are as effective or more effective than existing treatments.
By participating in these research projects, they are helping researchers get closer to a cure, contributing to the development of innovative molecules and improving the quality of life of all those who suffer or will suffer from the same disease.

📌 How can I participate in a Clinical Trial?

Participation in a trial or clinical study is voluntary, you may participate if:

Get invited by your doctor
Be aware of the existence of the trial and want to participate

New Breathe has the medical knowledge and experience to know the best clinical trials around the world for you.

📌 Clinical research is usually classified into 4 phases: I, II, III, and IV.

We must first remember that in order to clinically study a drug, it must have already been approved in preclinical tests, i.e., safety aspects are evaluated in experimental animals before this drug is applied to humans. When this medication is ready to be tested in humans, the phases of clinical investigation begin and follow one after the other, until as much information as possible about the drug is obtained.

Step I: refers to the use of the drug for the first time in a human being, usually a healthy individual who does not have the disease for which the drug is being studied. About 20 to 100 individuals participate in this phase.
Step II: About 100 to 300 individuals who have the disease or condition for which the procedure is being studied participate in this phase. Phase II tests usually different dosages as well as different indications of the new drug are also evaluated in this phase.
Step III: After the pilot study has been completed, large multicenter studies follow thousands of patients, 5,000 to 10,000 in general, depending on the pathology in question, for a longer period of time, usually being compared to other existing and recommended treatments for the same problem. The analysis of the data obtained in phase III may lead to the registration and approval for commercial use of the new drug or procedure by the health authorities.
Step IV: After a drug or a diagnostic/therapeutic procedure is approved and brought to market, follow-up tests on its use are designed and implemented in thousands of people, providing additional details about the safety and efficacy of the product. One of the important objectives of phase IV studies is to detect and define previously unknown or incompletely qualified side effects and related risk factors.

📌 If you are considering participating in a clinical trial, you should ask the clinical trial investigating physician all questions before agreeing to participate. You can, and should, ask questions about the clinical trial, its procedures, risks and benefits, or about alternative treatments, at any time. Some questions:

What is a clinical trial?
Who sponsors the clinical trial?
What is the purpose of this clinical trial? What are you investigating?
Who can participate?
How many patients will participate?
What is the duration of the clinical trial?
When participating, what are my rights? And my responsibilities?
What treatment will I receive? Can I choose? How long is the treatment?
What is the investigational drug? Do you know its advantage over existing ones? Are there any results already? How safe are they and the other drugs that will be used?
If I decide to participate, can I continue to take my usual medications?
What procedures (analyses/diagnostic tests) will be performed? Are there any invasive tests?
What risks will I take with my participation?
What benefits will I get from my participation?
Will my participation in the clinical trial affect my daily routine/work activity?
Will I be aware of the results?
Who can I contact when I have questions?
Will they always be with me?
What if I regret it and don’t want to continue participating?
I am currently receiving treatment, if I do not want to participate in the clinical trial, will I continue to receive treatment and medical assistance?
And if something goes wrong, how will I be treated or compensated?
Is there any insurance?
How will my personal and medical data be processed?
How is the confidentiality of my data kept?

New Breathe Team

New Breathe – services

Susana Ferreira

21/Sep/2021

Donanemab in Early Alzheimer’s Disease

A hallmark of Alzheimer’s disease is the accumulation of amyloid-β (Aβ) peptide. Donanemab, an antibody that targets a modified form of deposited Aβ, is being investigated for the treatment of early Alzheimer’s disease.

Methods

We conducted a phase 2 trial of donanemab in patients with early symptomatic Alzheimer’s disease who had tau and amyloid deposition on positron-emission tomography (PET). Patients were randomly assigned in a 1:1 ratio to receive donanemab (700 mg for the first three doses and 1400 mg thereafter) or placebo intravenously every 4 weeks for up to 72 weeks. The primary outcome was the change from baseline in the score on the Integrated Alzheimer’s Disease Rating Scale (iADRS; range, 0 to 144, with lower scores indicating greater cognitive and functional impairment) at 76 weeks. Secondary outcomes included the change in scores on the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog₁₃), the Alzheimer’s Disease Cooperative Study–Instrumental Activities of Daily Living Inventory (ADCS-iADL), and the Mini–Mental State Examination (MMSE), as well as the change in the amyloid and tau burden on PET.

Results

A total of 257 patients were enrolled; 131 were assigned to receive donanemab and 126 to receive placebo. The baseline iADRS score was 106 in both groups. The change from baseline in the iADRS score at 76 weeks was −6.86 with donanemab and −10.06 with placebo (difference, 3.20; 95% confidence interval, 0.12 to 6.27; P=0.04). The results for most secondary outcomes showed no substantial difference. At 76 weeks, the reductions in the amyloid plaque level and the global tau load were 85.06 centiloids and 0.01 greater, respectively, with donanemab than with placebo. Amyloid-related cerebral edema or effusions (mostly asymptomatic) occurred with donanemab.

Conclusions

In patients with early Alzheimer’s disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed. Longer and larger trials are necessary to study the efficacy and safety of donanemab in Alzheimer’s disease. (Funded by Eli Lilly; TRAILBLAZER-ALZ ClinicalTrials.gov number, NCT03367403)

Mark A. Mintun, M.D., Albert C. Lo, M.D., Ph.D., Cynthia Duggan Evans, Ph.D., Alette M. Wessels, Ph.D., Paul A. Ardayfio, Ph.D., Scott W. Andersen, M.S., Sergey Shcherbinin, Ph.D., JonDavid Sparks, Ph.D., John R. Sims, M.D., Miroslaw Brys, M.D., Ph.D., Liana G. Apostolova, M.D., Stephen P. Salloway, M.D., et al.

Alzheimer’s disease

Susana Ferreira

14/Sep/2021

Parkinson’s disease

Parkinson’s disease is a recognisable clinical syndrome with a range of causes and clinical presentations. Parkinson’s disease represents a fast-growing neurodegenerative condition; the rising prevalence worldwide resembles the many characteristics typically observed during a pandemic, except for an infectious cause. In most populations, 3–5% of Parkinson’s disease is explained by genetic causes linked to known Parkinson’s disease genes, thus representing monogenic Parkinson’s disease, whereas 90 genetic risk variants collectively explain 16–36% of the heritable risk of non-monogenic Parkinson’s disease. Additional causal associations include having a relative with Parkinson’s disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson’s disease. The diagnosis is clinically based; ancillary testing is reserved for people with an atypical presentation. Current criteria define Parkinson’s disease as the presence of bradykinesia combined with either rest tremor, rigidity, or both. However, the clinical presentation is multifaceted and includes many non-motor symptoms. Prognostic counselling is guided by awareness of disease subtypes. Clinically manifest Parkinson’s disease is preceded by a potentially long prodromal period. Presently, establishment of prodromal symptoms has no clinical implications other than symptom suppression, although recognition of prodromal parkinsonism will probably have consequences when disease-modifying treatments become available. Treatment goals vary from person to person, emphasising the need for personalised management. There is no reason to postpone symptomatic treatment in people developing disability due to Parkinson’s disease. Levodopa is the most common medication used as first-line therapy. Optimal management should start at diagnosis and requires a multidisciplinary team approach, including a growing repertoire of non-pharmacological interventions. At present, no therapy can slow down or arrest the progression of Parkinson’s disease, but informed by new insights in genetic causes and mechanisms of neuronal death, several promising strategies are being tested for disease-modifying potential. With the perspective of people with Parkinson’s disease as a so-called red thread throughout this Seminar, we will show how personalised management of Parkinson’s disease can be optimised.

Bastiaan R Bloem, Michael S Okun, Christine Klein

Parkinson’s disease

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