scholarly journals Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands

2021 ◽  
Author(s):  
Elise van Mulligen ◽  
Saad Ahmed ◽  
Angelique E. A. M. Weel ◽  
Johanna M. W. Hazes ◽  
Annette H. M. van der Helm- van Mil ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Personalized Medicine ◽  
Adverse Events ◽  
Real World ◽  
Tnf Inhibitor ◽  
Second Line ◽  
First Line ◽  
Negatively Associated ◽  
Autoantibody Status ◽  
Citrullinated Protein

AbstractWe aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0–7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3–2.2) and 0.8 years (95% CI, 0.5–1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32, p < 0.001) positively while RF positivity negatively (HR = 0.82, p = 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43, p = 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28, p = 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA. Key Points• Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored.• We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached.• The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.

scholarly journals Efficacy and Safety of Bevacizumab in Combination with Chemotherapy for Colorectal Cancer – A Real World Study in China

2020 ◽  
Author(s):  
Tao Shen ◽  
Xian-Shuo Cheng ◽  
Wei-Xun Chunyu ◽  
Hong-Tao Zhang ◽  
Cui-Feng Xia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Real World ◽  
Large Scale ◽  
Progression Free Survival ◽  
Secondary Outcome ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Demographic Subgroups

Abstract Background Large scale randomized trials have demonstrated that bevacizumab in addition to chemotherapy as first-line or second-line treatment has significant survival benefits. We aim to explore the clinical impact of bevacizumab in combination with chemotherapy in first-line or second-line in patients with colorectal cancer (CRC). Methods The medical records of patients with CRC who received bevacizumab at first or second-line of treatment were collected retrospectively. The primary outcome of the study was to evaluate the efficacy of bevacizumab in combination with chemotherapy by survival endpoints i.e. overall survival (OS) and progression-free survival (PFS) and the secondary outcome was to evaluate its safety by incidence of adverse events (AE). Results Fifty-one patients with CRC had met the selection criteria for treatment with bevacizumab to either cetuximab or FOLFOX or both. The median age was 54 years. During follow-up, ten patients had exhibited progression after treatment while 5 patients died. The median OS and PFS of the overall population were not reached. The Cox proportional regression analysis revealed no significant prognostic factors of OS and PFS for treatment with bevacizumab in various demographic subgroups. The 1-year PFS rates of all 51 patients was 76%. The 1-year and 3-year OS rates for all 51 patients were 95% and 88%, respectively. Toxicities were usually mild in nature, with nausea, vomiting, hand and foot syndrome, neutropenia, asthenia and palpitation being the commonly reported adverse events. Conclusion In this real-world setting, the efficacy and safety of bevacizumab in combination with chemotherapy is limited and further research is warranted as to whether bevacizumab with chemotherapy is an optimal treatment as first-line or second-line therapy in Chinese CRC patients.

scholarly journals POS0223 PATTERNS OF JANUS KINASE INHIBITOR CYCLING FOR THE MANAGEMENT OF RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL PRACTICE: AN ANALYSIS OF THE OPAL DATASET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 330-331
Author(s):  
S. Ciciriello ◽  
T. Smith ◽  
C. Osullivan ◽  
K. Tymms ◽  
P. Youssef ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Medical Record ◽  
Clinical Data ◽  
Real World ◽  
Visual Analytics ◽  
Clinical Care ◽  
Janus Kinase ◽  
Second Line ◽  
First Line ◽  
Third Line

Background:There are currently eleven biologic and targeted synthetic (b/ts)DMARDs acting via five different modes of action available for the treatment of RA in Australia. The cost of b/tsDMARDs is subsidized by government for patients that have active RA despite six months of combination csDMARD therapy. Once a patient is eligible, the clinician can prescribe the b/tsDMARD they deem to be the most clinically appropriate for the patient. In Oct 2015 the first JAK inhibitor (JAKi) became available in Australia (tofacitinib, TOF), baricitinib (BARI) became available in Sept 2018, and upadacitinib (UPA) in May 2020. Each of these oral tsDMARDs possess different selectivity profiles towards different members of the JAK family (JAK1–3 and Tyk2).Objectives:The aim of this analysis was to determine the patterns of JAKi cycling in real-world practice in Australia.Methods:Deidentified clinical data were sourced from the OPAL dataset, which is collected in a custom-built electronic medical record during the routine consultation1. Data from patients >18 years with RA who commenced a b/tsDMARD between Jan-2007 and Dec-2020 were included in the analysis. A visual analytics software program was used to display data on medication initiation and cessation dates, and reasons for stopping tsDMARDs, which is recorded in the medical record at the time of the decision.Results:At Dec 2020, 28% of the 52,190 patients with RA in the OPAL dataset were prescribed b/tsDMARDs. Of these patients, 3,850 (26.3%) were currently prescribed a JAKi with 51.4% receiving TOF, 29.2% BARI and 19.4% UPA. In 2020, JAKi initiations accounted for 48.8% of all initiations and 30.7% of 1st line initiations; an increase of 6.1% and 3.5% from 2019, respectively. The percentage of patients switching from a first line JAKi to a second line JAKi rather than an agent with another mode of action increased from 33.1% in 2019 to 42.6% in 2020. This is despite 26.2% in 2019 and 45.8% in 2020 of the patients switching to another JAKi citing lack of efficacy as the reason for JAKi discontinuation. In the period between May 2020, when a third JAKi (UPA) become available, and Dec 2020, the majority of patients switching from first line TOF or BARI to another JAKI switched to UPA (69.4% and 83.9%, respectively), whilst 30.6% of first line TOF patients switched to BARI (30.6%), and 16.1% of first line BARI patients switched to TOF in second line. The majority of patients switching from second line TOF or BARI to a third line JAKi switched to UPA (73% and 96%, respectively), with 27% of second line TOF patients switching to BARI and a very low number moving from second line BARI to TOF (4%). JAKi choice after a third line TOF or BARI was almost exclusively UPA (86.2% and 95.5%, respectively).Conclusion:There has been significant and sustained uptake of JAKi for the management of RA in Australia and JAKi cycling is increasingly common in routine clinical care. Clinical outcomes and persistence following JAKi cycling requires further investigation.References:[1]Littlejohn GO, Tymms KE, Smith T, Griffiths HT. Using big data from real-world Australian rheumatology encounters to enhance clinical care and research. Clin Exp Rheumatol. Sep-Oct 2020;38(5):874-880.Figure 1.Patterns of JAKi cycling for the management of rheumatoid arthritis in first, second and third line switching.Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platformDisclosure of Interests:Sabina Ciciriello: None declared, Tegan Smith: None declared, Catherine OSullivan: None declared, Kathleen Tymms: None declared, Peter Youssef: None declared, David Mathers: None declared, Claire Deakin: None declared, Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Geoff Littlejohn Speakers bureau: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus.

scholarly journals Systematic Literature Review on Global Real-World Treatment Patterns of Mantle Cell Lymphoma (MCL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5881-5881
Author(s):  
Keri Keri Yang ◽  
Beth Lesher ◽  
Eleanor Lucas ◽  
Tony Caver ◽  
Boxiong Tang
Keyword(s):  
Literature Review ◽  
Adverse Events ◽  
Real World ◽  
Treatment Options ◽  
Treatment Patterns ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line

Introduction: MCL is an aggressive type of non-Hodgkin's lymphoma, and was reported associated with early relapse and poor long-term survival. Treatment options include chemotherapy, immunotherapy, and molecular targeted therapies. As of 2019, molecular targeted therapies available in the United States indicated for the treatment of MCL include the proteasome inhibitor bortezomib, the immunomodulatory drug lenalidomide (following two previous lines of therapy), and the Burton's tyrosine kinase inhibitors (BTKIs) ibrutinib and acalabrutinib (following at least one previous line of therapy). Objective/Methods: To examine the real-world treatment patterns of patients with MCL globally, a systematic literature review was performed (2010-2019) with predefined methodology and inclusion and exclusion criteria. Embase and Medline were searched via ProQuest and the Cochrane Controlled Register of Trials (CENTRAL) via the Cochrane Library. Results: Of the 2207 publications identified, 6 publications (US, n = 4; EU, n = 2) provided information on the first-line treatment of MCL (Table). The most commonly administered first-line treatments were bendamustine-rituximab; high dose cytarabine ± rituximab; and cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) ± rituximab although differences were noted across studies. Most patients received rituximab first-line either in combination with chemotherapy (54.2%-87.5%) or as monotherapy (12.9%-28.9%); although in some studies, rituximab maintenance therapy could not be excluded. The most commonly administered second-line therapies were cytarabine, rituximab monotherapy, and ibrutinib while third-line therapies were rituximab monotherapy, ibrutinib, and temsirolimus. Nine studies provided data on the real-world treatment of MCL with the BTKI ibrutinib (EU, n = 3; US, n = 5; EU/US, n = 1; Table); no real-world studies were identified for acalabrutinib. Six studies enrolled patients only with relapsed or remitting MCL; 3 studies enrolled patients (≤7.5%) who received ibrutinib as first-line therapy. Ibrutinib second-line therapy was administered to 13%-20% of patients and third-line therapy to 21% of patients. Ibrutinib discontinuation rates in 7 studies varied from 38.7%-83.6%. Non-response, including relapse or progression (34.6%-100%), was the main cause of discontinuation, followed by toxicity/adverse events (8.1%-25.6%). Across studies, toxicity/adverse events causing ibrutinib discontinuation included atrial fibrillation, bleeding/hemorrhage, chronic obstructive pulmonary disease, diarrhea, herpes zoster, infection, leukocytosis/ lymphocytosis, lung cancer, myelodysplastic syndrome, and thrombocytopenia. Two studies provided information on ibrutinib dose reductions (16.4% of patients) and ibrutinib dose interruptions (7.8%-30.2% of patients). Treatment options administered post-ibrutinib included rituximab (52.7%), hyper-CVAD + rituximab (16.7%-25.8%), lenalidomide-based regimens (9.7%-41.5%), and bortezomib-based regimens (8.4%-34.4%). Conclusion: Our analyses showed that most patients with MCL received first-line chemoimmunotherapy, although regimens varied across studies. Approximately 13%-21% of patients received ibrutinib following first-line therapy. Most ibrutinib discontinuation was due to progression followed by toxicity/adverse events. Upon discontinuation of ibrutinib, considerable variation in treatments was seen and no standard therapy identified. Given the limitations of current therapies, there is a need for additional second- and third-line treatments for patients with MCL. Quantitative assessments of clinical endpoints from real-world studies evaluating BTKI therapies are also warranted. Disclosures Yang: BeiGene, Ltd.: Employment. Lesher:Pharmerit: Employment. Lucas:Pharmerit: Employment. Caver:BeiGene, Ltd.: Employment. Tang:BeiGene, Ltd.: Employment.

Real-world outcomes of second-line ramucirumab plus paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma: A nationwide retrospective study in Korea (KCSG-ST19-16).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4056-4056
Author(s):  
Dae Young Zang ◽  
Hye Sook Han ◽  
Bum Jun Kim ◽  
Hee-Jung Jee ◽  
Young Ju Suh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Adverse Events ◽  
Real World ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Real World Data

4056 Background: Ramucirumab as monotherapy or in combination with paclitaxel is a second-line treatment option recommended for patients with locally advanced unresectable or metastatic gastroesophageal junction (GEJ) or gastric adenocarcinoma. However, real-world data of large samples focused on ramucirumab plus paclitaxel in gastric cancer are limited. We conducted a nationwide retrospective study to evaluate the efficacy, safety, and factors potentially associated with survival in patients with gastric or GEJ adenocarcinoma who received second-line ramucirumab plus paclitaxel in a real-world setting. Methods: The study population comprised all patients with gastric or GEJ cancer who received ramucirumab plus paclitaxel in South Korea between May 1, 2018, and December 31, 2018. We included patients with advanced gastric or GEJ adenocarcinoma and disease progression after first-line platinum and fluoropyrimidine-containing combination chemotherapy. Results: A total of 1,063 patients with advanced gastric or GEJ adenocarcinoma who received ramucirumab plus paclitaxel were included. The objective response rate and disease control rate were 15.1% and 57.7%, respectively; the median progression-free survival was 4.03 months (95% CI, 3.80–4.27), and the median overall survival was 10.3 months (95% CI, 9.33–10.73). The common treatment-related adverse events (TRAEs) at any grade were neutropenia (44.7%), anemia (41.8%), neuropathy (29.1%), fatigue (25.9%), and anorexia (25.0%). Grade 3 or higher TRAEs with incidences of ≥5% were neutropenia (35.1%) and anemia (10.5%). Adverse events of special interest were infrequent, including hypertension (2.1%) and proteinuria (3.0%). Based on multivariate analysis, overall survival was negatively associated with Eastern Cooperative Oncology Group performance status ≥2, weight loss in the previous 3 months ≥10%, GEJ of primary tumor, poor or unknown histology grade, number of metastatic sites ≥3, presence of peritoneal metastasis, no prior gastrectomy, and time to second-line since first-line treatment < 6 months. Conclusions: Our large-scale, nationwide, real-world data analysis of an unselected real-world population added evidence for the efficacy and safety of second-line ramucirumab plus paclitaxel in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Clinical trial information: NCT04192734.

scholarly journals Real-world Data Analysis of Immunotherapy in Advanced Lung Cancer

2021 ◽  
Author(s):  
Meiling Sun ◽  
Huaijun Ji ◽  
Ning Xu ◽  
Peng Jiang ◽  
Tao Qu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Real World ◽  
Treatment Cycle ◽  
Advanced Lung Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Short Term ◽  
First Line Treatment

Abstract BackgroundThis study was designed to investigate the clinical application, efficacy, and safety of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer in the real world. MethodsA retrospective, observational analysis was conducted on patients treated with ICIs in four tertiary hospitals in the region from January 2015 to March 2021, to evaluate the clinical efficacy of ICI single-agent or combined chemotherapy and anti-vascular drugs in the first-line or second-line treatment of patients with advanced lung cancer. ResultsThree hundred and fifteen patients were enrolled in this study. The objective response rate (ORR) and disease control rate (DCR) were 36.5% (115/315) and 94.0% (296/315), respectively, the median progression-free survival (PFS) was 10.8 months, and the median overall survival (OS) was not reached. A total of 165 patients received ICI as the first-line treatment, the median treatment cycle was 8 cycles (2-20 cycles), the short-term efficacy ORR was 41.2%, DCR was 94.5%, and the median PFS was 12.0 months. 150 patients received ICI treatment as second-line treatment, the median treatment cycle was five cycles (2-10 cycles), the short-term efficacy ORR was 31.3%, DCR was 93.3%, and the median PFS was 10.0 months. There were no statistically significant differences in ORR, DCR, or median PFS with ICI as the first-line treatment compared with the second-line treatment(P>0.05). The results of subgroup analysis showed that Karnofsky performance status (KPS) score, EGFR mutation status, and number of treatment lines were not correlated with median PFS((P>0.05). However, there were statistically significant differences in programmed death-ligand 1(PD-L1) expression, pathological types, hormone interference, and antibiotic (Abx) treatment among all groups (P< 0.05). In terms of safety, the overall incidence of adverse reactions in 315 patients was 62.5%, and the incidence of immune-related adverse events(irAEs) was 13.7%. Grade 1-2 and 3-4 incidence of adverse events were 34.9% and 27.65%, respectively. There were four patients who experienced fatal irAEs, two cases were liver damage leading to liver failure, one case was immune related pneumonia, and one case was immune related myocarditis. ConclusionIn the real world, immunotherapy has a good effect on patients with advanced lung cancer and significantly improves ORR and PFS.

Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for foregut leaks and perforations

Endoscopy ◽  
2017 ◽  
Vol 50 (02) ◽  
pp. 148-153 ◽  
Author(s):  
Piero Valli ◽  
Joachim Mertens ◽  
Arne Kröger ◽  
Christoph Gubler ◽  
Christian Gutschow ◽  
...  
Keyword(s):  
Adverse Events ◽  
Success Rate ◽  
Vacuum Therapy ◽  
Line Treatment ◽  
Second Line ◽  
Metal Stent ◽  
First Line ◽  
Novel Technique ◽  
Upper Gastrointestinal ◽  
First Line Treatment

Abstract Background and study aims Endoluminal vacuum therapy (EVT) has evolved as a promising option for endoscopic treatment of foregut wall injuries in addition to the classic closure techniques using clips or stents. To improve vacuum force and maintain esophageal passage, we combined endosponge treatment with a partially covered self-expandable metal stent (stent-over-sponge; SOS). Patients and methods Twelve patients with infected upper gastrointestinal wall defects were treated with the SOS technique. Results Indications for SOS were anastomotic leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment was used as a first-line treatment in seven patients with a success rate of 71.4 % (5/7) and as a second-line treatment after failed previous EVT treatment in five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in 75 % of patients (9/12). No severe adverse events occurred. Conclusion SOS is an effective method to treat severely infected foregut wall defects in patients where EVT has failed, and also as a first-line treatment. Comparative prospective studies are needed to confirm our preliminary results.

Economic evaluation of crizotinib, alectinib, ceritinib, and brigatininb in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) as second-line treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21104-e21104
Author(s):  
Nimer S. Alkhatib ◽  
Briana Choi ◽  
Hala Halawah ◽  
Matthias Calamia ◽  
Dexter Gulick ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Incremental Cost ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Reference Drug ◽  
First Line Therapy ◽  
Line Therapy ◽  
Life Years

e21104 Background: Crizotinib, alectinib, ceritinib, and brigatinib are approved as second line treatment for ALK+ NSCLC. Crizotinib was the first ALK inhibitor for first line therapy approved by Food and Drug Administration (2011) then ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved as second line drugs. Following more data, these agents were approved as the first line therapy (2017 for ceritinib and alectinib; 2020 for brigatinib). These remain as a treatment option in patients who fail the first line therapy. Cost-effectiveness/utility analyses were conducted to assess clinical efficacy with varying costs of the agents. Methods: A three state Markov model were assumed (progression free, progression and death). Progression free survival (PFS) curves were digitized and fitted with exponential function. US payer perspective, a lifetime horizon, and discount rate of 3% were applied. Drug costs were Redbook wholesale acquisition cost. Other costs included were monitoring, adverse events and disease progression from published data (US$ 2020). Adverse events reported >5% in patients were included. Measured outcomes were PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Crizotinib was the reference drug. Incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) and lost were estimated. Base case (BCA) and probabilistic sensitivity analyses (PSA) were conducted. Results: Crizotinib was the reference drug for the following outcomes. For alectinib, with the decremental cost of -$14,653 (-$14,712), the incremental PFSLY of 0.16 (0.16) and PFSQALY of 0.05 (0.05) resulted in an ICER / PFSLYG of -$89,337 (-$88,604) and an ICUR / PFSQALYG of -$269,835 (-$266,510). For brigatinib, with the decremental cost of -$14,975 (-$14,954), the incremental PFSLY of 0.01 (0.01) and PFSQALY of ̃0.01 (0.02) yielded an ICER / PFSLYG of -$1,982,962 (-$1,431,631) and an ICUR / PFSQALYG of -$2,140,534 (-$570,538). For ceritinib, with the incremental cost of $7,590 ($7,514), there were decremental PFSLY of -0.01 (-0.01) and PFSQALY of -0.03 (-0.03). Conclusions: As second line treatment, crizotinib, ceritinib, and brigatinib had comparable PFSLYs and PFSQALYs while alectinib had the most PFSLY and PFSQALY and the lowest cost. Therefore, alectinib is the most cost-effective treatment for treating ALK+ NSCLC as the second line therapy.[Table: see text]

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