scholarly journals P272 How well are conventional DMARDs tolerated in PsA: a real-world study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Issrah Jawad ◽  
Muhammad K Nisar
Keyword(s):  
Side Effects ◽  
Real World ◽  
Retention Rate ◽  
Cost Effective ◽  
University Teaching ◽  
Duration Of Treatment ◽  
Real World Data ◽  
Nice Guidelines ◽  
Gi Symptoms ◽  
Conventional Dmards

Abstract Background NICE guidelines recommend the first line use of DMARDs in psoriatic arthritis (PsA). However, studies show that many conventional treatments like methotrexate are poorly tolerated. There is hitherto no published real-world data addressing the tolerability of DMARDs in PsA. Our objective was therefore to assess the drug management in PsA with focus on tolerability and the reasons for therapy cessation. Methods We conducted a retrospective analysis of all PsA patients enrolled in electronic database up to April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management. Results 335 patients were identified with a formal diagnosis of PsA. Mean age of the cohort was 46 years (13-81) and 58% were female. 9% of the individuals had diabetes and 18% had concurrent cardiovascular disease. 1/10th reported to be current smokers and 8% had a diagnosis of depression. 48% of the group had clinically active disease. Same percentage were taking a single DMARD. 10% had trialled 3 or more drugs. 62% of patients had discontinued one or more DMARDs prior. The mean duration before discontinuing a DMARD was 9.9 months. Methotrexate was the best tolerated and on average discontinued after 13.4 months (range: 4 days to 10.9 years). Sulfasalazine and hydroxychloroquine were discontinued after an average of 8.4 (11 days to 4.27 years) and 12.5 months (1.3 months to 2.88 years) respectively. Leflunomide was the least tolerated DMARD and stopped after an average of 5.5 months (7 days to 2.53 years). The main reason for stopping a medication was gastro-intestinal symptoms which accounted for 42% of all the reported side effects. This applied to both methotrexate (43%) and sulfasalazine (46%) discontinuation. The leading reasons for discontinuing hydroxychloroquine were jointly GI symptoms and other side effects at 43% each. Leflunomide was stopped in 50% of cases due to neurological symptoms. Conclusion To our knowledge, this is the first report confirming poor retention rate of oral DMARDs in a real world PsA cohort managed over 20 years. In the context of chronic disease, the median duration of treatment is short. Our analysis did not include patients who suffer from side effects but continue therapy thereby impacting treatment adherence and hence the true scale of the issue is likely higher. Though NICE guidelines stipulate the need of an adequate trial of minimum two DMARDs prior to therapy escalation, these drugs are not well tolerated and thus pose a challenge to clinicians. One potential solution is earlier adoption of biological therapies, which are increasingly cost effective and have been shown to be better tolerated. Disclosures I. Jawad None. M.K. Nisar None.

scholarly journals AB0810 IMPACT OF TOLERABILITY ON RETENTION OF cDMARDs IN PSORIATIC ARTHRITIS - IS IT A CONCERN?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1706.2-1707
Author(s):  
I. Jawad ◽  
M. K. Nisar
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Side Effects ◽  
Real World ◽  
Retention Rate ◽  
Cost Effective ◽  
University Teaching ◽  
Duration Of Treatment ◽  
Real World Data ◽  
Gi Symptoms

Background:Most guidelines recommend the first line use of DMARDs in Psoriatic Arthritis (PsA). However, studies show that many conventional treatments like methotrexate are poorly tolerated. There is hitherto no published real-world data addressing the tolerability of DMARDs in PsA.Objectives:Our objective was therefore to assess the drug management in PsA with focus on tolerability and the reasons for therapy cessation.Methods:We conducted a retrospective analysis of all PsA patients enrolled in electronic database up to April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease managementResults:335 patients were identified with a formal diagnosis of PsA. Mean age of the cohort was 46 years (13-81) and 58% were female. 48% of the group had clinically active disease. Same percentage were taking a single DMARD. 10% had trialled 3 or more drugs. 62% of patients had discontinued one or more DMARDs prior. The mean duration before discontinuing a DMARD was 9.9 months. Methotrexate was the best tolerated and on average discontinued after 13.4 months (range: 4 days to 10.9 years). Sulfasalazine and Hydroxychloroquine were discontinued after an average of 8.4 (11 days to 4.27 years) and 12.5 months (1.3 months to 2.88 years) respectively. Leflunomide was the least tolerated DMARD and stopped after an average of 5.5 months (7 days to 2.53 years). The main reason for stopping a medication was gastro-intestinal symptoms which accounted for 42% of all the reported side effects. This applied to both methotrexate (43%) and sulfasalazine (46%) discontinuation. The leading reasons for discontinuing Hydroxychloroquine were jointly GI symptoms and other side effects at 43% each. Leflunomide was stopped in 50% of cases due to neurological symptoms.Conclusion:To our knowledge, this is the first report confirming poor retention rate of oral DMARDs in a real world PsA cohort managed over 20 years. In the context of chronic disease, the median duration of treatment is short. Our analysis did not include patients who suffer from side effects but continue therapy thereby impacting treatment adherence and hence the true scale of the issue is likely higher. Though NICE guidelines stipulate the need of an adequate trial of minimum two DMARDs prior to therapy escalation, in reality these drugs are not well tolerated and thus pose a challenge to clinicians. One potential solution is earlier adoption of biological therapies, which are increasingly cost effective and have been shown to be better tolerated.Disclosure of Interests:Issrah Jawad: None declared, Muhammad Khurram Nisar Grant/research support from: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB, Consultant of: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB, Speakers bureau: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB

scholarly journals AB0809 HOW WELL ARE BIOLOGICS RETAINED IN PSORIATIC ARTHRITIS - A REAL WORLD STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1706.1-1706
Author(s):  
I. Jawad ◽  
M. K. Nisar
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Real World ◽  
Biologic Therapy ◽  
Health Economy ◽  
Nice Guidelines ◽  
Drug Survival ◽  
Gi Symptoms ◽  
Conventional Dmards ◽  
Significant Difference

Background:Biologics have led to a sea change in the management of psoriatic arthritis (PsA) with unprecedented improvement in the signs, symptoms and radiographic damage, resulting in improvement in functionality and quality of life. However longitudinal data for their retention and tolerability is sparse.Objectives:Our objective was to evaluate real-world biologic therapy duration and reasons for discontinuing treatment.Methods:We conducted a retrospective analysis of our PsA electronic register from 1994 up to and including April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management.Results:335 patients were identified with PsA. 58% of them were female with mean age of 46 yr (13-81). 113 (33.7%) patients had been treated with a biologic with 105 (93%) continuing at the time of analysis. 60 individuals were prescribed combination therapy with DMARDs. Mean age was 43.3 years (13-81) with 56% women. The biologics sample was ethnically diverse including 80% White Caucasian patients, 17% Asian and others (3%). Significant co-morbidities included cardiovascular disease (18.6%) and diabetes (4.4%). Eight different biologics were in use with adalimumab being the most prescribed (67%).35 (30.9%) patients had stopped biologics at some point with 76 episodes of cessation. 6% of our sample had discontinued two or more biologic treatments. The mean duration before biologic therapy was discontinued was 18.2 months (8 days to 9.5 years), which was almost twice as long as the average period before discontinuing a DMARD (9.9 months). Main reasons for stopping treatment included 23% each due to GI symptoms, neurological causes, cutaneous symptoms and other side effects. The remaining 8% reported fatigue as the reason for stopping therapy.Conclusion:To our knowledge this is the first dedicated retrospective review of a large real world PsA cohort comparing drug survival and tolerability of biologics against DMARDs. Biologic therapies are well tolerated in psoriatic arthritis. There is no significant difference amongst various modes of action. Over a quarter of the patients discontinue the drug owing to intolerance with mean drug survival of 18 months. In contrast nearly two-thirds were intolerant of DMARDs and stopped within ten months. Thus both the rate and duration of biologic retention is significantly better than conventional DMARDs. This has significant economic impact as NICE guidelines require an adequate trial of two DMARDs for six months prior to advanced therapy. However, this approach is unlikely to be cost effective as the disease progresses whilst patients struggle with DMARDs prescription and thus delay biologics which are more likely to be tolerated and retained longer. Hence there is an urgent need to review NICE guidelines to allow earlier employment of biologics in the treatment paradigm with significant benefits to both patients and the health economy.Disclosure of Interests:Issrah Jawad: None declared, Muhammad Khurram Nisar Grant/research support from: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB, Consultant of: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB, Speakers bureau: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB

scholarly journals P0331ASSESSMENT OF DELIVERY OF NICE APPROVED USE OF TOLVAPTAN (JINARC) IN ADULTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE IN A UK RENAL CENTRE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Aaron Acquaye ◽  
Kate Naylor ◽  
Sunil Bhandari
Keyword(s):  
Side Effects ◽  
Liver Enzymes ◽  
Retention Rate ◽  
Pressure Control ◽  
Lifestyle Changes ◽  
University Teaching ◽  
Initial Assessment ◽  
Teaching Hospitals ◽  
Duration Of Treatment ◽  
Tract Infections

Abstract Background and Aims Until recently, the management of ADPKD has largely been limited to lifestyle changes (smoking cessation, salt avoidance and diet with weight loss) and tight blood pressure control, in addition to kidney pain management and prompt treatment of complications such as infections. The approval of Tolvaptan, a highly selective vasopressin V2 receptor antagonist, by NICE, following the pivotal TEMPO 3:4 trial provides clinicians with an opportunity to modify the progression of ADPKD and preserve kidney function. Tolvaptan works by slowing cyst growth patients with ADPKD (and therefore potentially reducing kidney pain, urinary tract infections and haematuria). During the TEMPO 3:4 trial, a reversible elevation (> 3X upper limit) of liver enzymes was observed in 4.4% patients taking tolvaptan vs 1% on placebo. The onset of liver injury was between 3 – 14 months of initiation of tolvaptan; therefore, monthly blood tests are required to mitigate the potential injury associated with the increase in liver enzymes. The main side effects are polyuria and thirst. The aims for the audit were Method We carried out a prospective questionnaire-based study on all patients who were on tolvaptan therapy. All patients received a comprehensive explanation of the merits and side-effects of Tolvaptan with written literature and a copy of their initial assessment consultation prior to commencement of therapy. In addition, we reviewed patients’ clinic attendances, relevant biochemical results and liver function test as per licence agreement tolvaptan therapy. This was approved by the Hull University Teaching Hospitals (HUTH) NHS Trust Audit department with a signed Clinical Governance Form 1. Results In total, 27 patients, consisting of 18 males and 9 females [mean age 44.5yrs] and all Caucasian on tolvaptan therapy were evaluated. The median duration of treatment was 10months. Two patients [7.4%] dropped out of treatment: one patient opted out of treatment due to the polyuria interfering with his job requirements and the other had relocated to another country; giving HUTH a retention rate of 92.6%. 55.5% of patients responded to not having missed a dose of drug at any time at any time despite a significant number experiencing side-affects (Figure1). Some purposely missed medication due to a social event. Although 100% of patients did respond to experiencing side effects of tolvaptan, 74% of patients said it did not interfere with their quality of life. 88.8% of patients were on the full dose of 90mg in the morning and 30mg after 8 hours. The Tolvaptan clinic in HUTH is run as a pharmacist led with consultant oversight. Currently no issues have arisen but the patients’ view of a pharmacist led-clinic is currently being studied. Conclusion This study demonstrates that despite a number of expected side-affects; with good patient education and follow-up, few patients stopped therapy and most patients remain compliant to tolvaptan therapy. Currently a pharmacist led, consultant backed tolvaptan clinic has not adversely affected this success.

scholarly journals EP43 Biologic retention in psoriatic arthritis: a real world study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Issrah Jawad ◽  
Muhammad K Nisar
Keyword(s):  
Psoriatic Arthritis ◽  
Real World ◽  
Biologic Therapy ◽  
Health Economy ◽  
Nice Guidelines ◽  
Drug Survival ◽  
Advanced Therapy ◽  
Gi Symptoms ◽  
Conventional Dmards ◽  
Significant Difference

Abstract Background Biologics have led to a sea change in the management of psoriatic arthritis (PsA) with unprecedented improvement in the signs, symptoms and radiographic damage, resulting in improvement in functionality and quality of life. However longitudinal data for their retention and tolerability is sparse. Our objective was to evaluate real-world biologic therapy duration and reasons for discontinuing treatment. Methods We conducted a retrospective analysis of our PsA electronic register from 1994 up to and including April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management. Results 335 patients were identified with PsA. 58% were female with mean age 46 yr (13-81). 113 (33.7%) patients had been treated with a biologic with 105 (93%) continuing at the time of analysis. 60 individuals were prescribed combination therapy with DMARDs. Mean age was 43.3 (13-81) with 56% women. The biologics sample was ethnically diverse including 80% White Caucasian patients, 17% Asian and others (3%). Significant co-morbidities included cardiovascular disease (18.6%) and diabetes (4.4%). Eight different biologics were in use with adalimumab being the most prescribed (67%). 35 (30.9%) patients had stopped biologics at some point with 76 episodes of cessation. 6% of our sample had discontinued two or more biologic treatments. The mean duration before biologic therapy was discontinued was 18.2 months (8 days to 9.5 years), which was almost twice as long as the average period before discontinuing a DMARD (9.9 months). Main reasons for stopping treatment included 23% each due to GI symptoms, neurological causes, cutaneous symptoms and other side effects. The remaining 8% reported fatigue as the reason for stopping therapy. Conclusion To our knowledge this is the first dedicated retrospective review of a large real world PsA cohort comparing drug survival and tolerability of biologics against DMARDs. Biologic therapies are well tolerated in psoriatic arthritis. There is no significant difference amongst various modes of action. Over a quarter of the patients discontinue the drug owing to intolerance with mean drug survival of 18 months. In contrast nearly two-thirds were intolerant of DMARDs and stopped within ten months. Thus both the rate and duration of biologic retention is significantly better than conventional DMARDs. This has significant economic impact as NICE guidelines require an adequate trial of two DMARDs for six months prior to advanced therapy. However, this approach is unlikely to be cost effective as the disease progresses whilst patients struggle with DMARDs prescription and thus delay biologics which are more likely to be tolerated and retained longer. Hence there is an urgent need to review NICE guidelines to allow earlier employment of biologics in the treatment paradigm with significant benefits to both patients and the health economy. Disclosures: I. Jawad: None. M.K. Nisar: None.

Assessment and design of real world driving cycles targeted to the calibration of vehicles with electrified powertrain

2021 ◽  
pp. 146808742110387
Author(s):  
Stylianos Doulgeris ◽  
Zisimos Toumasatos ◽  
Maria Vittoria Prati ◽  
Carlo Beatrice ◽  
Zissis Samaras
Keyword(s):  
Real World ◽  
Simulation Models ◽  
Cost Effective ◽  
Operational Parameters ◽  
Virtual Design ◽  
Passenger Cars ◽  
Real World Data ◽  
Vehicle Simulation ◽  
Driving Cycles ◽  
The Impact

Vehicles’ powertrain electrification is one of the key measures adopted by manufacturers in order to develop low emissions vehicles and reduce the CO2 emissions from passenger cars. High complexity of electrified powertrains increases the demand of cost-effective tools that can be used during the design of such powertrain architectures. Objective of the study is the proposal of a series of real-world velocity profiles that can be used during virtual design. To that aim, using three state of the art plug-in hybrid vehicles, a combined experimental, and simulation approach is followed to derive generic real-world cycles that can be used for the evaluation of the overall energy efficiency of electrified powertrains. The vehicles were tested under standard real driving emissions routes, real-world routes with reversed order (compared to a standard real driving emissions route) of urban, rural, motorway, and routes with high slope variation. To enhance the experimental activities, additional virtual mission profiles simulated using vehicle simulation models. Outcome of the study consists of specific driving cycles, designed based on standard real-world route, and a methodology for real-world data analysis and evaluation, along with the results from the assessment of the impact of different operational parameters on the total electrified powertrain.

Abstract W P273: The Cost-Effectiveness of Telestroke Varies by Implementation Cost and Stroke Severity: Real World Data From a Pacific Northwest Network

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Elizabeth Baraban ◽  
Richard Nelson ◽  
Alexandra Lesko ◽  
Jennifer Majersik ◽  
Archit Bhatt ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Pacific Northwest ◽  
Real World ◽  
Cost Effective ◽  
Stroke Severity ◽  
Real World Data ◽  
World Data ◽  
Life Years ◽  
Implementation Costs ◽  
The Cost

Objective: An obstacle for community hospitals in joining a telestroke network is often the cost of implementation. Yet, previous analyses examining the cost and cost-effectiveness have only used estimates from the literature. Using real-world data from a Pacific Northwest telestroke network, we examined the cost-effectiveness of telestroke for spokes by level of financial responsibility for these costs and how this changes with patient stroke severity. Methods: We constructed a decision analytic model and parameterized it using patient-level clinical and financial data from the Providence Telestroke Network (PTN) pre and post telestroke implementation. Data included patients presenting at 17 spokes within 4.5 hours of symptom onset. Probability inputs included observed IV-tPA treatment rates, transfer status and hospital costs and reimbursements. Effectiveness, measured as quality-adjusted life years (QALYs), and cost per patient were used to calculate incremental cost effectiveness ratios (ICERs). ICER’s of <$50,000-$120,000/QALY are considered cost-effective. Outcomes were generated overall and separately by admit NIHSS, defined as low (0-10), medium (11-20) and high (>20) and percentage of implementation costs paid by spokes (0%, 50%, 100%). Results: Data for 594 patients, 105 pre- and 489 post-implementation, were included. See Table 1. Conclusions: Our results support previous theoretic models showing good value, overall. However, costs and ICERs varied by stroke severity, with telestroke being most cost-effective for severe strokes. Telestroke was least cost effective if spokes paid for half or more of implementation costs.

scholarly journals PDB66 - INSULIN GAP IN TYPE 2 DIABETES: IS IT COST EFFECTIVE TO INTENSIFY TREATMENT? EVIDENCE FROM PORTUGAL USING REAL WORLD DATA

2018 ◽  
Vol 21 ◽  
pp. S129
Author(s):  
F. Fiorentino ◽  
R. Ascenção ◽  
J. Costa ◽  
M. Gouveia ◽  
M. Borges
Keyword(s):  
Type 2 Diabetes ◽  
Real World ◽  
Cost Effective ◽  
Real World Data ◽  
World Data

scholarly journals Evaluating the Cost-Effectiveness of Early Compared with Late or No Biologic Treatment to Manage Crohn’s Disease using Real-World Data

2019 ◽  
Vol 14 (4) ◽  
pp. 490-500 ◽  
Author(s):  
Nadia Pillai ◽  
Judith E Lupatsch ◽  
Mark Dusheiko ◽  
Matthias Schwenkglenks ◽  
Michel Maillard ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Cost Effectiveness ◽  
Crohn's Disease ◽  
Health System ◽  
Real World ◽  
Transition Probabilities ◽  
Cost Effective ◽  
Real World Data ◽  
World Data ◽  
The Cost

Abstract Background and Aims We evaluated the cost-effectiveness of early [≤2 years after diagnosis] compared with late or no biologic initiation [starting biologics &gt;2 years after diagnosis or no biologic use] for adults with Crohn’s disease in Switzerland. Methods We developed a Markov cohort model over the patient’s lifetime, from the health system and societal perspectives. Transition probabilities, quality of life, and costs were estimated using real-world data. Propensity score matching was used to ensure comparability between patients in the early [intervention] and late/no [comparator] biologic initiation strategies. The incremental cost-effectiveness ratio [ICER] per quality-adjusted life year [QALY] gained is reported in Swiss francs [CHF]. Sensitivity and scenario analyses were performed. Results Total costs and QALYs were higher for the intervention [CHF384 607; 16.84 QALYs] compared with the comparator [CHF340 800; 16.75 QALYs] strategy, resulting in high ICERs [health system: CHF887 450 per QALY; societal: CHF449 130 per QALY]. In probabilistic sensitivity analysis, assuming a threshold of CHF100 000 per QALY, the probability that the intervention strategy was cost-effective was 0.1 and 0.25 from the health system and societal perspectives, respectively. In addition, ICERs improved when we assumed a 30% reduction in biologic prices [health system: CHF134 502 per QALY; societal: intervention dominant]. Conclusions Early biologic use was not cost-effective, considering a threshold of CHF100 000 per QALY compared with late/no biologic use. However, early identification of patients likely to need biologics and future drug price reductions through increased availability of biosimilars may improve the cost-effectiveness of an early treatment approach.

scholarly journals P232 Effectiveness of adalimumab biosimilar switching: real world data from a London rheumatology centre

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Shivanee Vigneswaran ◽  
Megan Galloway ◽  
Samuel Hanlon ◽  
Aoife Tynan ◽  
Animesh Singh
Keyword(s):  
Side Effects ◽  
Disease Activity ◽  
Real World ◽  
Biologic Therapy ◽  
Underlying Disease ◽  
Real World Data ◽  
Biologic Drugs ◽  
Control Activity ◽  
World Data ◽  
Long Term Treatment

Abstract Background Biologic drugs have revolutionised the management of many rheumatological diseases with remission or low disease activity now the realistic targets for treatment. However, given the chronic nature of most rheumatological disease and the need for long term treatment, there has been a significant increase in the cost associated with disease treatment. The advent of biosimilars offers an attractive target in reducing drug costs for payers. Biosimilar medications are thought to be equally efficacious as originator drugs. Real world data in adalimumab biosimilar switching is limited. In this audit we aim to examine the real-world outcomes from switching from originator Humira to biosimilar Amgevita in a London teaching hospital. Methods A list of all adult rheumatology patients on Amgevita was obtained through pharmacy records. All patients had been switched from Humira to Amgevita from February 2019. Using clinic letters and an in-house biologics database, data was collected on the underlying disease and the date of switch. Outcomes reviewed were disease activity scores pre and post switch, documented side effects and flare of disease activity following switch including decision to revert to originator Humira or change treatment. Results There was a total of 289 adult patients on Humira who switched to Amgevita. Of these patients, 28 in total discontinued treatment - 13 with rheumatoid arthritis, 10 with psoriatic arthritis and 5 with ankylosing spondylitis. 22 had to be switched back to Humira, with a further 4 patients approved to switchback and awaiting to restart. Two additional patients were switched to alternative biologic therapy due to inefficacy. A further 3 patients refused to switch onto Amgevita. Sixteen patients had documented flares, with one requiring admission and ten requiring local or systemic corticosteroid therapy to control activity. Seven patients had documented side effects which included chest pain, headache, rash and site reactions and one patient developed shingles post switch. Conclusion A total of 9.6% of patients switched to Amgevita had disease flare or side effects resulting in a switchback to Humira or alternative biologic therapy. For a biosimilar to be approved, efficacy and safety profiles needs to be comparable to the originator biological therapy and usually looks at two treatment naïve groups, rather than direct switch. Thereby, data on switches in therapy is limited. One systematic review looking at 11,053 patients with inflammatory arthritis treated with Etanercept and switched to Benepali, found 768 reverting to original therapy giving a lower total of 6.9%. We find that although no previous data of Amgevita, our figure of 9.6% appears high in the context of previously controlled inflammatory disease with Humira. Disclosures S. Vigneswaran None. M. Galloway None. S. Hanlon None. A. Tynan None. A. Singh None.

Real-world outcomes of ponatinib in treatment of advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitor (TKI) failure.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22508-e22508 ◽  
Author(s):  
Michael C. Heinrich ◽  
Lisa McGarry ◽  
David Kerstein ◽  
Hui Huang
Keyword(s):  
Real World ◽  
Kinase Inhibitor ◽  
Unmet Need ◽  
Rapid Progression ◽  
Phase 2 ◽  
Duration Of Treatment ◽  
Real World Data ◽  
Study Results ◽  
Starting Dose ◽  
Exon 11

e22508 Background: Imatinib is standard front-line treatment for advanced KIT+ GIST. For patients whose tumors progress on imatinib, sunitinib is indicated, followed by regorafenib for those with disease progression on both imatinib and sunitinib. Patients refractory to 2 prior TKIs typically experience rapid progression (median PFS: 4.8 mos for regorafenib; 0.9 mos for placebo [Demetri Lancet 2013]), and with failure of all approved TKIs, unmet need remains high. The oral TKI ponatinib, approved for TKI-refractory CML and Ph+ ALL, has shown activity in heavily-pretreated (76% with ≥4 prior regimens) advanced KIT+ GIST patients in a Phase 2, single-arm study (Heinrich ASCO 2015) at starting dose of 45 mg/day: clinical benefit rate (CBR = CR + PR + SD for ≥16 wks) of 37% and median PFS of 4.3 mos were observed in 30 patients with KIT exon-11-mutant GIST and CBR of 14% and median PFS of 2.0 mos in 15 patients whose GIST lacked a KIT exon 11 mutation. Methods: To examine real-world outcomes, we retrospectively identified patients receiving ponatinib off-label for GIST (ICD-9 171.5x, 171.9x) between 01Jan2014 and 31Dec2016 from sole-source US specialty-pharmacy records. Using patient, physician and pharmacy dispensing data, patient characteristics, treatment setting and dosing were noted, and duration of treatment (DOT) was examined using Kaplan-Meier techniques. Results: We identified 26 probable GIST patients receiving ponatinib over this 2-year period: 58% male; median age 57.5 yrs. Where reported, all received prior TKIs, but data for prior lines of therapy were incomplete. Most (69%) were treated in an academic setting, and the most frequent starting dose was 45 mg (77%). DOT ranged from < 1 to > 19 mos, with an estimated median DOT of 3.8 mos. At 3 mos, 61% of patients were estimated to remain on ponatinib, and at 6 mos, 34%. Conclusions: Available real-world data show that patients treated with ponatinib for TKI-refractory GIST had a median DOT of almost 4 mos, with 1/3 remaining on therapy for > 6 mos. Using DOT as a surrogate for PFS, these results are consistent with Phase 2 study results, and suggest ponatinib may have activity in patients who have exhausted other treatment options.

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