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 THU0209 UPTAKE OF JANUS KINASE INHIBITORS FOR MANAGEMENT OF RHEUMATOID ARTHRITIS IN AUSTRALIA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 329.2-329
Author(s):  
G. Littlejohn ◽  
T. Smith ◽  
K. Tymms ◽  
P. Youssef ◽  
H. Cooley ◽  
...  
Keyword(s):  
Adverse Reaction ◽  
Real World ◽  
Kinase Inhibitors ◽  
Clinical Laboratory ◽  
Clinical Care ◽  
Janus Kinase ◽  
Efficacy Rate ◽  
First Line ◽  
Data Set ◽  
Mode Of Administration

Background:JAK inhibitors (JAKi) are oral tsDMARDs with a different mode of action (MOA) to both oral cs- and parenteral bDMARDs. In Australia the cost of b/tsDMARDs for treatment of RA is subsidized if the patient has documented high levels of clinical/laboratory disease activity and has not responded to a pre-specified combination of csDMARDs, including MTX. Once eligible for subsidy the clinician can prescribe the b/tsDMARD deemed most clinically appropriate.Objectives:To determine the patterns of use and reasons for initiation and discontinuation of JAKi in real-world rheumatology practice in Australia.Methods:Deidentified clinical data were sourced from the OPAL dataset, which is collected in a custom-built electronic medical record at the time of the consultation1by 94 rheumatologists in Australia, representing one third of Australian clinical rheumatologists. Data from patients >18 years with a diagnosis of RA who commenced a b/tsDMARD between Jan-2007 and Sept-2019 were included in the analysis. Tableau®was used to display data on medication initiation and cessation dates, and reasons for starting and stopping b/tsDMARDs, which is recorded at the time of the decision.Results:At Sept 2019, there were 45,317 patients with RA in the data set, with 27% prescribed b/tsDMARDs. Of patients currently on treatment at Sept 2019, 53% were receiving a TNFi and 21% a JAKi, with the remainder receiving tocilizumab, abatacept or rituximab. Of patients who commenced their current treatment after JAKi’s become available in Sept 2015, 46% were treated with a TNFi, and 32% were treated with a JAKi. Tofacitinib (TOF) has been the most prescribed b/tsDMARD since Sept 2015 with 22% of all initiations; however, since baricitinib (BARI) became available in Sept 2018, it has taken over as the preferred JAKi with 24% of new initiations compared to 14% for TOF. From Sept 2018-Sept 2019 etanercept and adalimumab were the most commonly prescribed agents in first line, followed by TOF then BARI; however, BARI was the most prescribed agent in lines 2-6+ (figure 1). The main clinician-listed reason for choice of TOF was MOA in 54%, efficacy compared with alternatives in 30%, mode of administration in 7%, efficacy as monotherapy in 7%, and safety in 1%. BARI was chosen for MOA in 35%, efficacy compared with alternatives in 38%, mode of administration in 12%, efficacy as monotherapy in 12%, and safety in 1%. The main reasons for stopping TOF were lack of efficacy (34%), better alternative (25%) and adverse reaction (13%); those for BARI were lack of efficacy (35%) and adverse reaction (25%) which is consistent with the rates observed in the first 12-months of clinical experience with TOF, and better alternative (12%). Patient non-adherence was listed in 1% and 2% of cessations for TOF and BARI, respectively. 45% of patients discontinuing a JAKi in first line switched to a TNFi in second line, and 40% switched to another JAKi, citing lack of efficacy, adverse reaction, and better alternative as the reason for switching.Figure 1.Rank of new initiations by line of therapy (Sept 2018-Sept 2019)Conclusion:There has been significant and sustained uptake of JAKi for the management of RA in Australia. MOA and perceived efficacy rate much higher than mode of administration for clinicians when selecting a JAKi. Clinical outcomes and persistence following JAKi cycling requires further investigation.References: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 Rheum Nov 2019Disclosure of Interests:None declared

Clinical efficacy and safety in gastric cancer patients treated with apatinib: A retrospective real-world study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15522-e15522
Author(s):  
Ning Li ◽  
Yali Du ◽  
Wenying Deng ◽  
Yijie Ma ◽  
Xinyi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Efficacy ◽  
Real World ◽  
Neoadjuvant Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Her2 Positive ◽  
Her2 Mutation ◽  
Third Line

e15522 Background: This study aimed to explore the efficacy, safety of apatinib and analyze the effects of HER2 mutation status and treatment lines on gastric cancer (GC) patients (pts) treated with apatinib in real-world clinical practice. Methods: We retrospectively analyzed the study data from Linkdoc database with 270 pts who were pathologically or cytologically diagnosed GC and treated with apatinib during January 2015 to November 2018 in Henan Cancer Hospital. Survival was estimated by Kaplan-Meier method. Results: In this study, there were 180 (66.7%) male, with median age of 59 years. The vast majority of pts (259/95.9%) had adenocarcinoma and 86.3% of pts were in stage IV. HER2 was positive in 33.0% of 100 treated pts undergoing HER2 mutation testing. Apatinib was mainly used as second-line treatment (122/45.2%), followed by third-line (82/30.4%), first-line (56/20.7%), fourth- and further-line (22/8.1%), adjuvant (12/4.4%) and neoadjuvant treatment (1/0.4%). Pts received apatinib alone or combined with chemotherapy were 175 (64.8%) and 119 (44.1%), with 53.6% administered at an initial dose of 500 mg. Of all the 270 enrolled pts, the median progression free survival (mPFS) and median overall survival (mOS) were 4.3 months (95% CI: 3.5-5.0) and 6.1 months (95% CI: 5.1-8.4), respectively. For treatment lines subgroup, the mOS was 12.6 months (95% CI: 3.5-NE) in adjuvant treatment; 8.9 months (95% CI: 4.3-12.6) in first-line; 7.3 months (95% CI: 5.0-9.7) in second-line; 6.2 months (95% CI: 5.1-9.9) in third-line; 4.0 months (95% CI: 1.6-6.9) in fourth- and further-line treatment. For HER2-negative pts, the mOS was slightly longer than those of HER2-positive pts (5.7 months vs. 4.5 months), however, the difference was not statistically significant ( p = 0.5185). The most common adverse events were fatigue (25.9%), anemia (24.8%), hypertension (9.3%) and vomiting (9.3%). Conclusions: This real world study revealed that the clinical efficacy of apatinib in GC pts was satisfying and the toxicity was tolerable and controllable. Pts received apatinib in ≤ second-line treatment may gain better survival benefits, and little difference was found in survival outcomes between pts with or without HER2 mutations.

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.

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.

Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A retrospective real world study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 113-113 ◽  
Author(s):  
Yang Chen ◽  
Guanghai Dai
Keyword(s):  
Real World ◽  
Large Scale ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Her2 Positive ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2 ◽  
Third Line

113 Background: Although the clinical trial WJOG7112G was failed to prove weekly paclitaxel with trastuzumab in patients with HER2-positive gastric or gastro-esophageal junction (GEJ) cancer refractory to trastuzumab is better than paclitaxel alone, there are limited data concerning efficacy of continuing trastuzumab beyond first-line progression in the real world. Methods: This retrospective study included all consecutive patients with HER2-positive advanced gastric or GEJ adenocarcinoma who received a chemotherapy with trastuzumab in first-line, or second-line, or third-line therapy between 2010 and 2016 in Chinese People’s Liberation Army General Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated from the initial chemotherapy. Results: A total of 67 patients (median age, 59 years; male, 71.6%) with HER-2 positive advanced gastric or GEJ adenocarcinoma treated with chemotherapy plus trastuzumab initially in first (n = 50), second (n = 13), or third (n = 4) line of therapy were included. The median OS of trastuzumab for initial first-line, second-line, or third-line treatment was 16.7 months, 14.2 months, and 13.2 months, respectively (P = 0.83). In patients initially using trastuzumab in first-line therapy, the continuation (n = 19) versus discontinuation (n = 31) of trastuzumab beyond first-line progression was significantly associated with an improvement of median PFS (3.4 versus 1.9 months; P = 0.02), but not OS (19.0 versus 16.4 months; P = 0.13). In the multivariate analysis including the ECOG PS, number of metastatic sites and chemotherapy regimen, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.77; 95% CI, 0.41-0.93; P = 0.04), but not OS (HR, 0.85; 95% CI, 0.56-1.22; P = 0.24). Conclusions: This study suggests that HER-2 positive advanced gastric or GEJ adenocarcinoma patients could benefit from trastuzumab no matter when they start receiving trastuzumab. The continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer for PFS, but not for OS. Large scale prospective randomized validation is warranted.

scholarly journals Results of an International, Multi-Centre, Retrospective Study to Describe Treatment Pathways, Outcomes and Resource Use in Patients with Multiple Myeloma in Emerging Markets (INTEGRATE)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3045-3045
Author(s):  
Kihyun Kim ◽  
Natalia Paola Schutz ◽  
Su-Peng Yeh ◽  
Estelle Verburgh ◽  
Fahad Alsharif ◽  
...  
Keyword(s):  
Emerging Markets ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Bone Lesions ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Advisory Committees ◽  
Third Line

Abstract Introduction: Multiple myeloma (MM) is a progressive, rarely curable, B-cell malignancy (McCachren et al. 2021). The incidence is increasing, with the greatest acceleration in emerging markets (Cowan et al. 2016). Optimal management amidst emerging treatments is challenging (Bruno et al. 2020; Mohty et al. 2020). This study aimed to obtain real-world data on treatment, toxicity and healthcare utilization in patients with MM in emerging markets. Methods: INTEGRATE is an international, multi-center, retrospective, observational study of the medical records of alive or deceased patients aged ≥18 years with newly diagnosed (NDMM) or relapsed/refractory (RRMM) disease between 1 January 2010 and 31 December 2011 (Figure 1). The primary objective was to describe the time to next treatment (TTNT) at each line of therapy. Results: Patient records were screened at 45 centers across Argentina, China, Republic of Korea, Russia, Saudi Arabia, South Africa, Taiwan and Turkey. In the NDMM group (N=1,511), patients were followed up for a median 56.9 months, 50.6% were male and predominantly White (50.2%) or Asian (37.9%). The mean age at diagnosis was 59.6 years (range 24.4-97.3 years). Most patients (51.4%) had immunoglobulin G (IgG) myeloma, and 32.0% had IgG kappa and were staged using International Staging System criteria (49.6%). Many patients had bone lesions in 1-3 sites (43.3%) and a majority had no fluorescence in situ hybridization data reported. There were 481 (31.8%) patients who underwent frontline stem-cell transplantation (SCT), of the 987 patients who did not, 121 (12.3%) were eligible for transplant. In the RRMM group (N=621), patients were followed up for a median 62.2 months, 50.1% were male, 57.0% White and 32.2% Asian. The mean age at diagnosis was 57.9 years (range 17.7-86.4 years). Most patients (52.5%) had IgG myeloma, 33.5% had IgG kappa, and 44.1% had bone lesions in more than three sites. Of the 144 patients eligible for SCT at the relapsed/refractory diagnosis, 98 (68.1%) underwent transplantation. The median time on first-line therapy was 6.0 months (interquartile range [IQR] 3.7-10.4), 6.4 months (IQR 3.2-11.9) at second line and 6.6 months (IQR 3.3-9.6) at third line for NDMM patients. In the RRMM group, the median time on first-line therapy was 5.7 months (IQR 3.5-9.0), 6.0 months (IQR 3.3-9.5) at second line and 6.0 months (IQR 3.1-10.9) at third line. The most common first-line therapies are shown in Table 1. The median TTNT for patients with NDMM was 39.5 months (95% confidence interval [CI] 37.6-42.6) at first line, 33.9 months (95% CI 28.8-37.0) at second line and 20.9 months (95% CI 17.1-27.1) at third line (Figure 2). In the non-SCT NDMM subgroup, 44% of patients had documented relapse or disease progression after first-line treatment and the 5-year OS rate was 64.6% (95% CI 61.2-67.9). In the SCT NDMM subgroup, 43.2% of patients had documented relapse or progression after first-line treatment and the 5-year OS rate was 73.5% (95% CI 69.1-77.4). In a risk factor analysis, Asian ethnicity (p&lt;0.001), bone marrow plasma cells at diagnosis (p&lt;0.001), no SCT performed frontline for NDMM (p=0.001), ISS stage II/III and the presence of either t(4;14), t(14;16) or del 17p13 (p=0.022) were associated with shorter TTNT in the NDMM patients. Conclusions: INTEGRATE is the largest real-world study to describe the management of MM across these eight emerging markets that remains reflective of the treatments currently available in these countries. We found time on therapy not dissimilar to cohorts in Europe and the US (Mohty et al. 2020; Hari et al. 2018) although the real-world OS appears longer than previous reports from Japan (Akizuki et al. 2020) and the US (Bruno et al. 2020). In addition, median duration of treatment during the first 3 lines of therapy are also very similar to that reported by Kwee et al. 2016. The INTEGRATE study highlights a wide variation between the TTNT and duration of treatment and has the potential to inform screening and management decisions based on available treatments to maximize lines of therapy. Figure 1 Figure 1. Disclosures Kim: Janssen, BMS: Research Funding. Schutz: Takeda: Honoraria; Johnson & Johnson: Honoraria; Sanofi: Honoraria. Mitina: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Chng: Novartis: Honoraria, Research Funding; Antengene: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; AbbVie: Honoraria; Amgen: Honoraria; BMS/Celgene: Honoraria, Research Funding; Johnson & Johnson: Honoraria, Research Funding; Takeda: Honoraria; Aslan: Research Funding. Wu: Takeda: Current Employment, Current equity holder in publicly-traded company. Wan: Takeda: Current Employment. Huang: Takeda: Current Employment, Current equity holder in publicly-traded company. Beksac: BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals POS0619 MODELLING OF DISEASE ACTIVITY IN PATIENTS WITH INFLAMMATORY ARTHROPATHIES TREATED WITH ETANERCEPT ORIGINATOR OR BIOSIMILAR AS FIRST-LINE BIOLOGIC IN AN AUSTRALIAN REAL-WORLD DATASET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Data ◽  
Real World ◽  
Rank Test ◽  
P Value ◽  
Continuous Variables ◽  
Linear Quadratic ◽  
First Line ◽  
Modest Improvement ◽  
Over Time

Background:The availability of biosimilars as non-proprietary versions of established biologic disease-modifying anti-rheumatic drugs (bDMARDs) is enabling greater access for patients with rheumatic diseases to effective medications at a lower cost. Since April 2017 both the originator and a biosimilar for etanercept (trade names Enbrel and Brenzys, respectively) have been available for use in Australia.Objectives:[1]To model effectiveness of etanercept originator or biosimilar in reducing Disease Activity Score 28-joint count C reactive protein (DAS28CRP) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with either drug as first-line bDMARD[2]To describe persistence on etanercept originator or biosimilar as first-line bDMARD in patients with RA, PsA or ASMethods:Clinical data were obtained from the Optimising Patient outcomes in Australian rheumatoLogy (OPAL) dataset, derived from electronic medical records. Eligible patients with RA, PsA or AS who initiated etanercept originator (n=856) or biosimilar (n=477) as first-line bDMARD between 1 April 2017 and 31 December 2020 were identified. Propensity score matching was performed to select patients on originator (n=230) or biosimilar (n=136) with similar characteristics in terms of diagnosis, disease duration, joint count, age, sex and concomitant medications. Data on clinical outcomes were recorded at 3 months after baseline, and then at 6-monthly intervals. Outcomes data that were missing at a recorded visit were imputed.Effectiveness of the originator, relative to the biosimilar, for reducing DAS28CRP over time was modelled in the matched population using linear mixed models with both random intercepts and slopes to allow for individual heterogeneity, and weighting of individuals by inverse probability of treatment weights to ensure comparability between treatment groups. Time was modelled as a combination of linear, quadratic and cubic continuous variables.Persistence on the originator or biosimilar was analysed using survival analysis (log-rank test).Results:Reduction in DAS28CRP was associated with both time and etanercept originator treatment (Table 1). The conditional R-squared for the model was 0.31. The average predicted DAS28CRP at baseline, 3 months, 6 months, 9 months and 12 months were 4.0 and 4.4, 3.1 and 3.4, 2.6 and 2.8, 2.3 and 2.6, and 2.2 and 2.4 for the originator and biosimilar, respectively, indicating a clinically meaningful effect of time for patients on either drug and an additional modest improvement for patients on the originator.Median time to 50% of patients stopping treatment was 25.5 months for the originator and 24.1 months for the biosimilar (p=0.53). An adverse event was the reason for discontinuing treatment in 33 patients (14.5%) on the originator and 18 patients (12.9%) on the biosimilar.Conclusion:Analysis using a large national real-world dataset showed treatment with either the etanercept originator or the biosimilar was associated with a reduction in DAS28CRP over time, with the originator being associated with a further modest reduction in DAS28CRP that was not clinically significant. Persistence on treatment was not different between the two drugs.Table 1.Respondent characteristics.Fixed EffectEstimate95% Confidence Intervalp-valueTime (linear)0.900.89, 0.911.5e-63Time (quadratic)1.011.00, 1.011.3e-33Time (cubic)1.001.00, 1.007.1e-23Originator0.910.86, 0.960.0013Acknowledgements: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 platform.Supported in part by a research grant from Investigator-Initiated Studies Program of Merck & Co Inc, Kenilworth, NJ, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co Inc, Kenilworth, NJ, USA.Disclosure of Interests:Claire Deakin: None declared, Geoff Littlejohn Consultant of: 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., Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Tegan Smith: None declared, Catherine OSullivan: None declared, Paul Bird Speakers bureau: Eli Lilly, abbvie, pfizer, BMS, UCB, Gilead, Novartis

scholarly journals AB0337 TOFACITINIB MONOTHERAPY OR COMBINED WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS SHOW SIMILAR RETENTION OVER FOUR YEARS. REPORT FROM RHUMADATA ®

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1467.1-1467
Author(s):  
D. Choquette ◽  
L. Bessette ◽  
L. Choquette Sauvageau ◽  
I. Ferdinand ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Treatment Initiation ◽  
Retention Rate ◽  
Janus Kinase ◽  
P Value ◽  
Research Support ◽  
Medication Discontinuation ◽  
Kaplan Meier

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

Sign in / Sign up

Export Citation Format

Share Document