scholarly journals P282 Outcome for PsA biologic switchers following primary inefficacy of TNFi therapy in a secondary care cohort: sequential TNFi versus switching mode of action

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Meena Naja ◽  
Liliana R Santos ◽  
Muhammad Shipa ◽  
Greenwood Mandy ◽  
Madhura Castelino
Keyword(s):  
Mode Of Action ◽  
Real Life ◽  
Initial Therapy ◽  
Current Evidence ◽  
First Line ◽  
Test Analysis ◽  
Drug Survival ◽  
Clinical Biomarkers ◽  
Switching Mode ◽  
Drop Outs

Abstract Background TNFi are the most used first line of biologic disease modifying anti-rheumatic drugs (bDMARDs) in PsA. In primary loss of response (PLR) to TNFi, there is no current evidence that directs the choice of second line bDMARDs. Our aim in this work was to compare drug survival for those who switched to a second TNFi versus alternative agents in real life. Methods Data was analysed retrospectively from a cohort of 400 PsA patients followed through from 2002-2019. Statistical analysis was carried out with descriptive statistics and t-test analysis using SPSS version 22. Results Out of 400 patients, 220 (55.0%) were started on bDMARD treatment. Of these 220, 212 (96.5%) were started on TNFi as initial therapy. PLR was seen in 42 of these patients (19.8%). The median drug survival of initial TNFi therapy was 7.1 months (interquartile range [IQR] 3.6 - 53.4 months). Of the 42 patients with PLR: 32 (76.2%) were switched to a second TNFi; 6 (14.3%) were switched to ustekinumab and 4 (9.5%) were switched to secukinumab. 21 of the 32 patients switched to a second TNFi were subsequently switched onto a third biologic due to treatment failure (65.6%). The median drug survival of the second TNFi in this group was 7.7 months (IQR 3.0 - 26.3 months). 3 out of the 6 (50%) patients who were switched to ustekinumab were then subsequently switched, this was due to primary inefficacy in 66.7% and adverse events in 33.3%. The median drug survival of ustekinumab in this group was 10.0 months (IQR 0.0 - 16.0 months). All 4 patients switched to secukinumab continue on this treatment with no drop outs, giving a median drug survival 12.3 months (IQR 6.5 - 19.5 months). Conclusion Our data suggests that patients with PLR to TNFi in PsA who switched mode of action to IL-17 inhibitor appeared to have better drug survival than subsequent TNFi or IL-12/23 inhibitors. Exploring the clinical biomarkers for those with successful switch to non-TNFi bDMARD in a larger cohort would help with targeting the most appropriate individuals and early disease control. Disclosures M. Naja None. L. R. Santos None. M. Shipa None. G. Mandy None. M. Castelino None.

scholarly journals Switching to riociguat: a potential treatment strategy for the management of CTEPH and PAH

2020 ◽  
Vol 10 (1) ◽  
pp. 204589401983784
Author(s):  
Raymond L. Benza ◽  
Paul A. Corris ◽  
Hossein-Ardeschir Ghofrani ◽  
Manreet Kanwar ◽  
Vallerie V. McLaughlin ◽  
...  
Keyword(s):  
Life Experience ◽  
Soluble Guanylate Cyclase ◽  
Real Life ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Cyclic Guanosine Monophosphate ◽  
Initial Therapy ◽  
Guanosine Monophosphate ◽  
Current Evidence ◽  
Off Label ◽  
Insufficient Response

Currently, five classes of drug are approved for the treatment of pulmonary arterial hypertension (PAH): phosphodiesterase 5 inhibitors (PDE5i); endothelin receptor antagonists; prostacyclin analogs; the IP receptor agonist selexipag; and the soluble guanylate cyclase (sGC) stimulator riociguat. For patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), riociguat is currently the only approved pharmacotherapy. Despite the development of evidence-based guidelines on appropriate use of specific drugs, in clinical practice patients are often prescribed PAH-targeted therapies off label or at inadequate doses. PDE5i are the most often prescribed class of drugs as initial therapy, either alone or in combination with other drug classes. However, a proportion of patients receiving PAH therapies do not reach or maintain treatment goals. As PDE5i and riociguat target different molecules in the nitric oxide-sGC-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway, for patients with PAH without an initial or sustained response to PDE5i, there is a biological rationale for switching to riociguat. However, robust data from randomized controlled trials on the safety and efficacy of switching are lacking, as is formal guidance for clinicians. Here we review studies of sequential combination therapy, and trial data and case studies that have investigated switching between PAH-approved therapies, particularly from PDE5i to riociguat in patients with PAH with an insufficient response to PDE5i, and in patients with CTEPH who were receiving off-label treatment. These studies summarize the current evidence and practical real-life experience on the concept of switching treatments.

scholarly journals AB0312 REAL-LIFE DATA ON THE USE OF BIOLOGICAL DMARDS IN RHEUMATOID ARTHRITIS IN AUSTRIA WITH SPECIAL ATTENTION TO SWITCHING AFTER FIRST BDMARD FAILURE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1455.1-1455
Author(s):  
V. Nell-Duxneuner ◽  
B. Reichardt ◽  
T. Stamm
Keyword(s):  
Rheumatoid Arthritis ◽  
Mode Of Action ◽  
Real Life ◽  
Social Health Insurance ◽  
Tnf Inhibitors ◽  
The Other ◽  
Social Health ◽  
Special Focus ◽  
Tnf Inhibitor ◽  
Drug Survival

Background:The introduction of biological disease modifying anti-rheumatic drugs (bDMARDs) offered new dimensions in controlling disease progress for patients with Rheumatoid Arthritis (RA). According to the recommendations by EULAR, treatment should be commenced with a conventional synthetic DMARD as soon as diagnosis is made, followed by a bDMARD after treatment failure. The choice of drug is done in respect to comorbidities, preference of the patient and to costs.Objectives:Drug expenditure data of 2012-2016 were retrieved to evaluate frequency of prescription and drug survival with special focus on switching habits after first bDMARD failure.Methods:Data were extracted from 11 Austrian social health insurance funds covering 86% of the Austrian population. Only patients with first prescriptions of bDMARDs were included. Absolute and relative frequencies of first bDMARD prescriptions, second and third courses of bDMARDs (switches) and probabilities of drug survival of first line bDMARDs were calculated. Baselines were set individually at the beginning of the first bDMARD course. A Sankey diagram was used to illustrate the relationships between first, second and third courses of bDMARDs (Figure). The first left column represents the first bDMARDs, the second and third columns the second and third switched bDMARDs, respectively. The quantity of the bDMARDs is reflected in the width of the lines.Results:7637 RA patients on bDMARD therapy were retrieved in total. With a presumed prevalence of 0.5% (Ref) this would account for 27% of RA patients being treated with a bDMARD. Of these, 3813 were first time prescriptions. The most commonly prescribed drug in bDMARD naïve patients was Etanercept with 26%, followed by Adalimumab with 25%. Third was Tocilizumab followed by Golimumab (16% and 15%), Abatacept with 9% and Certolizumab and Infliximab with both 4%. Tocilizumab showed the longest drug survival with 80% after one and 61% of patients still on the drug after 3 years. Golimumab was clearly favorable among TNF inhibitors with a drug survival of 71% after one and 50% after 3 years compared to Certolizumab showing the lowest with 63% after one year and only 38% after three years. Tocilizumab was the drug most often switched to after first course failure, followed by Adalimumab. The choice of second bDMARD was different: After Adalimumab failure more patients were switched to another mode of action (almost 50%), predominately Tocilizumab. This is also seen after Golimumab failure and is less pronounced in the other TNF inhibitors: they were mostly switched to second TNF inhibitor, mainly Adalimumab. The majority of patients started on Tocilizumab and Abatacept were switched to a TNF inhibitor (74% and 58%, respectively). In third DMARD choice again Tocilizumab is mostly chosen followed by Abatacept, leaving 42% to a TNF inhibitor, mostly Golimumab.Conclusion:Patients were most often started on a TNF inhibitor as first bDMARD, namely Etanercept and Adalimumab. Golimumab was prescribed less often but showed the longest drug survival among TNF inhibitors. Tocilizumab showed the longest drug survival overall and was the bDMARD most often switched to as second bDMARD. When starting with Adalimumab or Golimumab there was a tendency towards change of mode of action, which was not as pronounced for the other three TNF inhibitors. After failing twice Tocilizumab and Abatacept were the most often prescribed drugs.References:[1]Kobelt G, Fasteng F: Access to Innovative Treatments in Rheumatoid Arthritis in Europe. A Report prepared for the EFPIA, 2009Acknowledgments:Austrian Main Social Health Association (Dachverband österreichische Sozialversciherung)Disclosure of Interests:Valerie Nell-Duxneuner Speakers bureau: MSD, Pfizer, Jansen, Abbvie, Lilly, Novartis, Berthold Reichardt: None declared, Tanja Stamm Grant/research support from: AbbVie, Roche, Consultant of: AbbVie, Sanofi Genzyme, Speakers bureau: AbbVie, Roche, Sanofi

Initial therapy for chronic myelogenous leukemia: playing the odds.

1998 ◽  
Vol 16 (9) ◽  
pp. 2897-2903 ◽  
Author(s):  
S J Lee ◽  
C Anasetti ◽  
M M Horowitz ◽  
J H Antin
Keyword(s):  
Initial Therapy ◽  
Myelogenous Leukemia ◽  
Rational Approach ◽  
Current Evidence ◽  
Newly Diagnosed ◽  
First Line ◽  
Curative Therapy ◽  
First Line Therapy ◽  
Selection Of ◽  
Better Than

For patients with newly diagnosed CML, the life expectancy is much better than it was 5 years ago. However, with improvements in both transplant and nontransplant therapy comes controversy over optimal first-line therapy. We argue that an evidence-based analysis that weighs the likelihoods of surviving transplantation and responding to interferon should help guide selection of initial therapy. Such a strategy would aggressively triage appropriate patients to curative therapy while advising those who are unlikely to do well with transplantation to elect less toxic therapy, which still confers a survival benefit. We realize that many other factors beside the ones mentioned here affect a clinician's recommendation for initial therapy and a patient's ultimate choice. Many extenuating circumstances, coexisting medical conditions, and personal values need to be a part of the ultimate decision. However, we hope that this guideline summarizes the current evidence and offers a rational approach to help guide newly diagnosed patients.

scholarly journals OP0288 ANTI-IL1 TREATMENT IN COLCHICINE RESISTANT PEDIATRIC FMF PATIENTS-REAL LIFE DATA FROM THE HELIOS REGISTRY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 179.1-180
Author(s):  
E. Sag ◽  
F. Akal ◽  
E. Atalay ◽  
U. Kaya Akca ◽  
S. Demir ◽  
...  
Keyword(s):  
Age At Onset ◽  
Real Life ◽  
First Line ◽  
Research Support ◽  
Skin Reactions ◽  
Local Skin ◽  
Extreme Stress ◽  
On Demand ◽  
Drug Registry ◽  
Treatment Onset

Background:FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine resistant/intolerant FMF patients.Objectives:We aimed to investigate the efficacy and safety of anti-IL1 treatment in pediatric FMF patients in our local (HELIOS) registry.Methods:HELIOS (Hacettepe univErsity eLectronIc research fOrmS) is a web-based biological drug registry for pediatric rheumatology patients (helios.hacettepe.edu.tr). Data were recorded at biological treatment onset (month 0), at month 6 and yearly thereafter in patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agent.Results:Forty pediatric FMF patients were included to the study group (67% female).Thirty-four patients received continous anti-IL1 treatment. The mean age at the start of the colchicine was 5.55±3.87 years. Age at onset of the anti-IL1 treatment was 11.47±5.41 with a mean follow-up duration of 3.87±1.96 years. Apart from two patients, all of them had biallelic exon-10 mutations.We have also given anti-IL1 treatment on an on-demand basis in six adolescent patients. Five of them were having very severe attacks during menstrual periods and one was having attacks during extreme stress periods along with very high CRP levels. The quality of life has markedly improved and these patients no longer reveal any CRP elevation.Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients were treated with canakinumab. Anti-IL1 treatment decreased the CRP levels, number and severity of the attacks. (Figure 1.) There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leukopenia with anakinra and one patient had thrombocytopenia with canakinumab. We have discontinued anti-IL1 treatment until the cytopenia subsided. We have switched to on-demand therapy in one patient, started the same treatment and gradually increased the dose in the other two patients. There were no malignancy or other severe adverse reactions.Figure 1.Conclusion:Anakinra and canakinumab are efficient and safe alternatives in colchicine resistant and intolerant pediatric FMF patients. We also for the first time, report on-demand use of anti-IL1 in pediatric FMF patients. We suggest that on-demand treatment should be considered under certain circumstances where the trigger is known and short-lasting (such as menstruation and periods of extreme stress)Acknowledgments:Authors would like to thank Elif Arslanoglu Aydin, Armagan Keskin, Kubra Yuksel and Emil Aliyev for their contribution to the HELIOS registryDisclosure of Interests:Erdal Sag Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Fuat Akal Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Erdal Atalay Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ummusen Kaya Akca Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Selcan Demir Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Dilara Demirel Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ezgi Deniz Batu Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Yelda Bilginer Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis

Real-world clinical outcomes study of sequential novel antihormonal therapy (NAH) or radium-223 (Ra-223) treatment of metastatic castration-resistant prostate cancer (mCRPC) that progressed after first-line NAH.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 48-48
Author(s):  
Oliver A. Sartor ◽  
Daniel J. George ◽  
Bertrand Tombal ◽  
Celestia S. Higano ◽  
Cora N. Sternberg ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Real Life ◽  
Patient Characteristics ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Highly Active ◽  
Radium 223 ◽  
Alpha Emitter ◽  
Antihormonal Therapy ◽  
The Usa

48 Background: We assessed real-life clinical outcomes in patients with mCRPC treated in the USA who received sequential first-line (1L)/second-line (2L) NAH (abiraterone/enzalutamide or enzalutamide/abiraterone) or switched to a different mechanism of action (alpha-emitter Ra-223) after progression on 1L NAH. Methods: This was a retrospective study (PHENIX, NCT03896984) of the Flatiron electronic health record database in patients with mCRPC that progressed on 1L NAH and started 2L monotherapy with Ra-223 (n=120) or NAH (n=226) between Jan 2013 and Dec 2018. Patient characteristics, overall survival (OS) from 2L start, and symptomatic skeletal events (SSEs) were analyzed descriptively. Results: The two cohorts were generally similar at 2L start, including similar rates of bone-health agent (BHA) use, but the Ra-223 cohort had a higher incidence of bone-only metastases, shorter duration of 1L NAH, and higher rate of prior SSEs than the 2L NAH cohort (Table). Median treatment duration was 5.6 mo (median 4.5 doses) for Ra-223 and 4.7 mo for 2L NAH. Median OS from 2L start was 10.8 mo for Ra-223 and 11.2 mo for 2L NAH, with 49% and 39%, respectively, receiving subsequent therapy. Among those who received subsequent therapy, the proportion who received subsequent taxane was lower in the Ra-223 cohort (47%) than in the 2L NAH cohort (76%). SSEs were observed after 2L start in 32 patients (27%) on Ra-223 and 49 (22%) on 2L NAH. Conclusions: OS from start of 2L mCRPC treatment was similar for patients who received Ra-223 or alternative NAH in 2L. Slightly more patients received subsequent therapy in the Ra-223 cohort than in the 2L NAH cohort. Patients who received subsequent therapy were more likely to receive chemotherapy in the 2L NAH cohort, which is unsurprising as 2L NAH after 1L NAH is not highly active. Although the prior SSE rate before 2L start was higher in the Ra-223 cohort than in the 2L NAH cohort, and the two cohorts had similar rates of BHA use at 2L start, the rate of SSEs after 2L start was similar in both cohorts. Clinical trial information: NCT03896984. [Table: see text]

1206P UNcommon EGFR mutations: International Case series on efficacy of Osimertinib in Real-life practice in first-liNe setting (UNICORN)

2021 ◽  
Vol 32 ◽  
pp. S961-S962
Author(s):  
J. Bar ◽  
W. Kian ◽  
M. Wolner ◽  
S. Derijcke ◽  
N. Girard ◽  
...  
Keyword(s):  
Real Life ◽  
Case Series ◽  
Egfr Mutations ◽  
First Line ◽  
Line Setting

The development of a cognitive rehabilitation and psycho-social group programme for teenage and young adult survivors of brain tumours: A feasibility study

2021 ◽  
pp. 135910452110555
Author(s):  
Daniel Glazer ◽  
Xeni Daniilidi ◽  
Charlotte Valentino
Keyword(s):  
Young Adult ◽  
Feasibility Study ◽  
Social Group ◽  
Brain Tumours ◽  
Cognitive Rehabilitation ◽  
Real Life ◽  
Adult Survivors ◽  
Strategy Training ◽  
Current Evidence ◽  
Current Evidence Base

Introduction and aims Treatment for childhood and adolescent brain tumours is often intensive, with significant neurocognitive and psycho-social late effects ( Zeltzer et al., 2009 ). This feasibility Study aimed to inform the development of a cognitive rehabilitation and psycho-social group intervention for Teenage and Young Adult (TYA) survivors of brain tumours. Methods A group-based intervention incorporated ideas from the current evidence base, including psychoeducation and compensatory strategy training, with a focus on real-life goals and improving quality of life. Participants ( N = 19, 13–24 years) were recruited from the University College London Hospital TYA Oncology Service. Participants had received treatment for a malignant brain tumour and had completed their treatment at least 1 year prior to participation. Four group-based, whole-day interventions ran every 3 months throughout a year. Feasibility criteria were established to answer questions about acceptability of the intervention and recruitment. Results Qualitative and quantitative feedback from all four groups demonstrated acceptability and suitability of the intervention with regards to the content, structure and delivery. Recruitment presented more of a challenge with 35% fewer referrals than expected. Discussion and conclusion Feedback suggests that the intervention is suitable and acceptable, whilst limitations include numbers of referrals and referral pathways. Future directions are discussed.

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