Comparing the Cost Per Treatment Success of Thrombopoietin Receptor Agonists to Watch & Rescue for the Treatment of Primary Adult Chronic Immune Thrombocytopenia (ITP) in the US

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4640-4640
Author(s):  
Kelly Northridge ◽  
Mark Danese ◽  
Robert Deuson
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Treatment Success ◽  
Response Rates ◽  
Thrombopoietin Receptor Agonists ◽  
Overall Response ◽  
Platelet Counts ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor ◽  
The Us

Abstract Abstract 4640 OBJECTIVES: To compare the drug costs relative to response of two thrombopoietin receptor agonists, romiplostim and eltrombopag, to Watch & Rescue for the treatment of chronic immune thrombocytopenia (ITP), from a health plan perspective. ITP, a diagnosis of exclusion, is characterized by low platelet counts and, depending on platelet count level, increased risk of bleeding (Rodeghiero F, et al. Blood. 2009:113(11):2386–2393). METHODS: An Excel® model compared 2011 US drug costs (wholesale acquisition cost) to the overall patient response rates (four or more weekly platelet counts of ≥50 × 109/L during the study from week 2 to 25) observed in individual 6-month placebo-controlled trials for romiplostim, eltrombopag, and placebo (or Watch & Rescue) (http://www.nice.org.uk/nicemedia/live/12025/50715/50715.pdf). These trials studied patients with median baseline platelet counts of 16 × 109/L (in both the romiplostim and eltrombopag trials) with 51% of the eltrombopag and 64% of the romiplostim patients receiving ≥3 previous treatments prior to joining each respective trial (Kuter, D, et al. Lancet. 2008:371:395–403; Cheng G, et al. Lancet. 2011:377:393–402; Bussel, J, et al. Lancet. 2009:373:641–648). The model considers a 55 mg daily dose of eltrombopag, and an average dose (including wastage) derived from a trial-based simulation for the US of 286 mcg per weekly administration of romiplostim. It assumes that 30% of US patients are splenectomized. The model considers a 1 g/kg overall dose of IVIg per rescue event at an average romiplostim trial-based weighted average (by splenectomy status) rate of 2.29 administrations per 6-month period (Weitz, I, et al. Curr Med Res Opin. 2012:28(5):789–796). RESULTS: For romiplostim patients, the expected cost of treating a patient with romiplostim over a 6-month period (trial period) is $34,655, with an overall response rate of 83%, or a cost per patient with an overall response of $41,753 ($34,655÷83%). The expected 6-month cost of treating the same patient with eltrombopag is $28,516, for an overall response rate of 57%, or a cost per patient with an overall response of $50,028 ($28,516÷57%). Comparatively, the expected 6-month cost of treating the same patient with Watch & Rescue is $11,681, with an overall response rate of 9%, or a cost per patient with an overall response of $129,789 ($11,681÷9%). Patients treated with thrombopoietin receptor agonists experience a 48 to 74% higher overall response rates than patients treated with Watch & Rescue, at a 153 to 196% reduction in resources to achieve the response. Sensitivity analyses were performed on key variables; a ±50% change in the average 6-month cost of IVIg (from either a decrease in cost or a decrease in the average number of administrations) resulted in ±50% change in the Watch & Rescue cost per response ($64,894 to $194,683). A decrease of 25% to the response rates for romiplostim and eltrombopag individually resulted in a 33% increase in the overall cost per patient with an overall response to $55,670 for romiplostim and $66,704 for eltrombopag. CONCLUSIONS: In chronic adult ITP, the use of thrombopoietin receptor agonists represents an efficient use of healthcare resources, with better health outcomes at a significantly lower cost per treatment success than treatment with Watch & Rescue. Disclosures: Northridge: Amgen Inc.: Consultancy, Research Funding. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

scholarly journals The Effects of a Between-Wave Incentive Experiment on Contact Update and Production Outcomes in a Panel Study

2013 ◽  
Vol 29 (2) ◽  
pp. 261-276 ◽  
Author(s):  
Katherine A. McGonagle ◽  
Robert F. Schoeni ◽  
Mick P. Couper
Keyword(s):  
Data Collection ◽  
Overall Response Rate ◽  
Response Rate ◽  
Panel Study ◽  
Response Rates ◽  
Income Dynamics ◽  
Overall Response ◽  
Percentage Points ◽  
Contact Information ◽  
The U.S

Abstract Since 1969, families participating in the U.S. Panel Study of Income Dynamics (PSID) have been sent a mailing asking them to update or verify their contact information in order to keep track of their whereabouts between waves. Having updated contact information prior to data collection is associated with fewer call attempts, less tracking, and lower attrition. Based on these advantages, two experiments were designed to increase response rates to the between wave contact mailing. The first experiment implemented a new protocol that increased the overall response rate by 7-10 percentage points compared to the protocol in place for decades on the PSID. This article provides results from the second experiment which examines the basic utility of the between-wave mailing, investigates how incentives affect article cooperation to the update request and field effort, and attempts to identify an optimal incentive amount. Recommendations for the use of contact update strategies in panel studies are made.

The Emergence of Thrombopoietin Receptor Agonists as a Novel Treatment for Immune Thrombocytopenia

2011 ◽  
Vol 07 (01) ◽  
pp. 63 ◽  
Author(s):  
Roberto Stasi ◽  
Elizabeth Rhodes ◽  
Reuben Benjamin ◽  
Hubertus Buyck ◽  
Fenella Willis ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Phase Iii ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor ◽  
The Us ◽  
Favourable Side Effect Profile ◽  
Proven Efficacy ◽  
Phase Iii Trials ◽  
Clinical Trial Results

Two thrombopoietin receptor agonists, romiplostim and eltrombopag, have completed phase III trials in patients with chronic immune thrombocytopenia and were shown to successfully improve platelet counts. Due to their proven efficacy and favourable side-effect profile, they have been granted marketing authorisation for use in this condition in the US, the EU and other countries. This article focuses on these two agents, their pre-clinical development and clinical trial results.

Mycophenolate Mofetil and Thrombopoietin Receptor Agonists in the Treatment of Refractory Thrombocytopenia in Patients with Autoimmune Lymphoproliferative Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2218-2218
Author(s):  
Leejah Chang ◽  
Susan Price ◽  
Katie Perkins ◽  
Joie Davis ◽  
Patricia Aldridge ◽  
...  
Keyword(s):  
Platelet Count ◽  
High Dose ◽  
Autoimmune Lymphoproliferative Syndrome ◽  
Thrombopoietin Receptor Agonists ◽  
Platelet Counts ◽  
Receptor Agonists ◽  
50Mg Daily ◽  
Thrombopoietin Receptor ◽  
Lymphoproliferative Syndrome

Abstract Abstract 2218 Autoimmune lymphoproliferative syndrome (ALPS), often due to an inherited defect in the FAS gene, presents with chronic non-malignant lymphadenopathy, splenomegaly, and autoimmune cytopenias (Oliveira JB et al. “Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop”. Blood. 2010 Oct 7;116(14):e35-40). Thrombocytopenia has been noted in approximately 23% of ALPS patients. These patients, especially those with massive splenomegaly and hypersplenism, are often refractory to standard dose short-term corticosteroid regimens and intravenous immunoglobulins (IVIG). Mycophenolate mofetil (MMF) has been used for persistent thrombocytopenia as a steroid sparing long-term measure in 40 out of 245 ALPS patients in our cohort. The median age at initiation of MMF was 10.5 years (range 7 months to 43 years) with an average follow-up of 3.8 years on MMF (range 3 months to 11 years). Here we share our experience over the last 7 months related to the use of thrombopoietin receptor agonists in 3 ALPS patients who have persistent, severe, MMF-refractory thrombocytopenia (platelets <10,000/uL) (Figure). Patient 1 is a 21 year old man with ALPS-FAS and splenomegaly who has been on MMF for 2 years. He presented with monthly episodes of thrombocytopenia requiring high dose corticosteroids and IVIG followed by four weeks of rituximab and daily prednisone without any durable improvement in his thrombocytopenia. He was started on eltrombopag 50mg daily and was able to taper off prednisone in one month with sustained stable platelet count. Three months after starting eltrombopag, he was able to survive surgical intervention for a spontaneous pneumothorax while on eltrombopag and MMF. Patient 2 is an 18 year old woman with ALPS-FAS and surgical asplenia who has been on MMF for approximately 7 years. She began having significant, symptomatic thrombocytopenia refractory to high-dose corticosteroids with transient responses to IVIG. She was started on eltrombopag 50mg daily with MMF and initially responded. However, when MMF was discontinued her platelet count plummeted. Despite reinitiating MMF, her platelet counts never recovered on eltrombopag and she continued to require monthly IVIG. She was eventually switched to romiplostim, and was incrementally increased to the maximum dose of 10mcg/kg/week. Her platelet counts continue to fluctuate, but she has not required any IVIG in over one month. Patient 3 is a 19 year old man with ALPS-U and surgical asplenia who has been on MMF for the last 9 years. During the past year he has had episodes of symptomatic thrombocytopenia requiring monthly courses of high dose corticosteroids and IVIG. After initiation of eltrombopag, he had a significant rise in his platelet counts. However, upon discontinuation of MMF, his platelet counts plummeted. MMF was restarted and he was trialed on multiple, different eltrombopag dosing regimens leading to supratherapeutic responses with platelet counts over 1,000,000/uL. Eltrombopag was held during these periods to allow for the significant thrombocytosis to resolve, but withholding eltrombopag led to platelet counts to eventually fall precipitously. Furthermore, he also developed severe headaches due to MMF and MMF had to be discontinued. After multiple dosing regimens, he eventually maintained a stable platelet count on eltrombopag 50mg daily for 5 days alternating with eltrombopag 25mg for 2 days without the concomitant use of MMF. Recently, there has been increasing evidence supporting the use of thrombopoietin receptor agonists in the treatment of refractory immune thrombocytopenia. MMF continues to be well tolerated as a long-term corticosteroid sparing drug for patients with ALPS complicated by chronic, refractory thrombocytopenia. Our preliminary experience suggests that there may be a role for thrombopoietin receptor agonists, most likely in combination with an immunosuppressive agent such as MMF, in the treatment of refractory thrombocytopenia in patients with ALPS. However, schedule and duration of therapy with this class of drugs needs further long term evaluation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Safety, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Adult Patients with Primary Immune Thrombocytopenia: A Randomized, Double-Blind and Placebo-Controlled Phase 1b Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 16-16
Author(s):  
Renchi Yang ◽  
Hu Zhou ◽  
Yu Hu ◽  
Jie Yin ◽  
Junmin Li ◽  
...  
Keyword(s):  
Treatment Period ◽  
Overall Response Rate ◽  
Response Rate ◽  
Double Blind ◽  
Durable Response ◽  
Overall Response ◽  
Platelet Counts ◽  
Primary Immune Thrombocytopenia ◽  
Phase 1B ◽  
Dose Levels

Abstract Background: Primary immune thrombocytopenia (ITP) is characterized by increased platelet destruction and impaired platelet production, resulting in decreased platelet counts and increased bleeding risk. Spleen Tyrosine Kinase (Syk) plays a pivotal role in the regulation of downstream signals in immune receptors, including B cell receptors (BCRs) and has been implicated in autoantibody production. On the other hand, all activating Fc receptors signal via Syk, which has roles in cellular proliferation, differentiation, survival, immune regulation, and cytoskeletal rearrangements during phagocytosis. This randomized, double-blind, placebo-controlled phase 1b study (NCT03951623) aimed to assess the safety, pharmacokinetics (PK), determine the recommended phase 2 dose (RP2D) and evaluate preliminary efficacy of HMPL-523, a novel, potent and highly selective Syk inhibitor, in patients with ITP. Methods: Relapsed/refractory ITP patients with platelet counts less than 30×10 9/L were eligible for the study. This randomized study (3:1) consists of two stages with dose escalation (DES) and dose expansion (DEX). Four dose groups were set (100, 200, 300 and 400mg QD) and patients were randomized to either HMPL-523 or placebo in each dose group (n=8) to determine the RP2D in DES. Additional 12 patients were enrolled at RP2D to further assess the safety and efficacy in DEX. Each patient received an 8-week double blind treatment (8w-DB), followed by a 16-week, open-label HMPL-523 treatment (16w-OL), except for all patients of 100mg cohort and 2 patients of 200mg cohort (only received 8w-DB per protocol v1.0). Treatment-emergent adverse events were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. The efficacy of overall response rate was defined as the proportion of patients with at least one platelet counts ≥50×10 9/L, and durable response rate was defined as the proportion of patients with platelet counts ≥50×10 9/L for at least 4 of the last 6 scheduled visits. Results: As of data cutoff (June 23, 2021), 33 patients (24:9) were enrolled in DES at 100-400mg. And 300mg QD was determined as RP2D. Additional 12 patients (10:2) were enrolled in DEX at 300mg QD. Main baseline patient characteristics are shown in Table 1. During 8-w DB treatment period, the overall response rate was 3 (50.0%), 2 (33.3%), 11 (68.8%) and 2 (33.3%) at 100-400mg dose cohorts, respectively, compared to 1 (9.1%) in the placebo. The durable response rate at 300mg was 5 (31.3%), compared to 1 (9.1%) in placebo. For all patients enrolled in 300mg cohort with at least one dose of HMPL-523 (n=20), including both 8w-DB and 16w-OL treatment period, the overall response rate was 80%; the durable response rate was 27.8% in the durable response-evaluable set (defined as patients received HMPL-523 treatment and completed at least 6 scheduled visits or discontinued during HMPL-523 treatment, n=18). No DLTs were observed at 100-400mg dose cohorts. The most common TEAEs (≥2 patients) related with HMPL-523 in 8w-DB were LDH increased (6 [17.6%]), ALT increased (5 [14.7%]), amylase increased (5 [14.7%]), AST increased (4 [11.8%]), neutrophil count decreased (3 [8.8%]), hypokalemia (3 [8.8%]), urine protein detection (3 [8.8%]), WBC count decreased (3 [8.8%]), gamma-glutamyl transferase (2 [5.9%]), asthenia (2 [5.9%]), dizziness (2 [5.9%]), total bile acid increased (2 [5.9%]), diarrhea (2 [5.9%]), abdominal pain (2 [5.9%]), hypertriglyceridemia (2 [5.9%]) and hyperlipidemia (2 [5.9%]). For all patients enrolled in 300mg cohort (n=20) throughout HMPL-523 treatment period (up to 24 weeks), ALT increased (5 [25.0%]), LDH increased (5 [25.0%]), AST increased (4 [20.0%]), total bile acid increased (4 [20.0%]), amylase increased (3 [15.0%]), TBiL increased (2 [10.0%]), hyperlipemia (2 [10.0%]) and hypertension (2 [10.0%]) were the most frequently reported HMPL-523-related TEAEs (≥2 patients). At the dose of 100-400mg QD, the exposure of HMPL-523 (C max and AUC tau) in plasma increased dose proportionally. Median T max was 4 h and mean T 1/2 was 11-13 h across all four dose levels. Conclusion: HMPL-523 was well tolerated at all dose levels within the range of 100 mg to 400 mg. HMPL-523 300mg QD for ITP treatment is an efficacious and safe dose and recommended as RP2D. A randomized phase 3 study will commence to further confirm the efficacy of HMPL-523 in primary ITP. Figure 1 Figure 1. Disclosures Shi: HUTCHMED: Current Employment. Yin: HUTCHMED: Current Employment. Fan: Hutchmed: Current Employment.

scholarly journals Efficacy of Thrombopoietin Receptor Agonists in Evans Syndrome: An International Multicenter Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3155-3155
Author(s):  
Nicola Cecchi ◽  
Juri Alessandro Giannotta ◽  
Andrea Patriarca ◽  
Andreas Glenthøj ◽  
Maria Eva Mingot ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rates ◽  
Advisory Board ◽  
Evans Syndrome ◽  
Advisory Committees ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor

Abstract Background: Evans syndrome (ES) is a rare condition, defined as the presence of two autoimmune cytopenias (AIC), more frequently autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), and rarely autoimmune neutropenia (AIN). ES can be classified as primary or secondary to various conditions, including lymphoproliferative disease (LPD), primary immune deficiencies (PID) or other systemic autoimmune diseases (AID). ES onset may be acute and life-threatening, whilst its clinical course is usually chronic and marked by several relapses of AIHA, ITP or both. First line therapy is based on steroids +/- intravenous immunoglobulins (IVIG), followed by rituximab and splenectomy in refractory/relapsing cases. Concerning ITP, splenectomy is not always feasible, and rituximab is poorly effective on the long term. Thrombopoietin receptors agonists (TPO-RA), such as romiplostim (ROMI) and eltrombopag (EPAG), are commonly used in primary ITP with high efficacy; however, their use in ES has never been systematically studied. Aim: to evaluate the efficacy and safety of TPO-RA in a multicentric cohort of patients with ES. Methods: all ES patients treated with TPO-RA at 8 European hematologic hospitals (3 Italian, 2 Danish, 1 United Kingdom and 2 Spanish) were retrospectively evaluated. Baseline hematologic parameters, associated conditions, previous treatments and those administered concomitantly to TPO-RA were registered. The time from diagnosis to first TPO-RA was collected. Response rates were evaluated at 1, 3, 6, and 12 months, and classified as partial (PR) or complete (CR), for platelets &gt;30x10^9/L or &gt;100x10^9/L, respectively. Treatment emergent adverse events (TAEs) were registered and graded according to CTCAE. R esults: As shown in Figure 1, 22 ES patients have been evaluated, 9 of whom secondary (40%). Almost all patients had received steroids +/- IVIG, and the majority at least one further line. The median time from diagnosis to TPO-RA start was 25,74 months (1-1390). Response rates to the first TPO-RA (16 EPAG and 6 ROMI) were: 82% at month 1, 84% at month 3, 83% at month 6 and 93% at month12. Eight patients started TPO-RA within 1 year from ES diagnosis. These patients displayed significantly lower platelets (p=0.01) as compared to others, however response rates were comparable. Of note, 73% of patients required concurrent therapies, including steroids +/- IVIG (N=13), danazol (N=2), rituximab (N=3), and immunosuppressants (N=3). Moreover, 7 patients required the addition of a rescue therapy to control ITP (steroids +/- IVIG N=4, rituximab N=1, danazol N=1, daratumumab N=1, immunosuppressants N=2, parsaclisib N=1), particularly in secondary ES (63% vs 33%). The latters less frequently showed increased bone marrow megakaryocytes (67% vs 92%) but had higher dysplasia (50% of patients vs 33% in primary ES). Interestingly, 5 subjects switched to the alternative TPO-RA (3 ROMI to EPAG and 2 vice versa) 2 because of no response (NR), and 3 for relapses. Three subjects responded but required additional therapies, including splenectomy, steroids +/- IVIG, or platelet transfusions. Ten out of 22 patients developed at least one TEAE: G1 thrombocytosis (N=1), G2 bone marrow fibrosis (N=1), G3/4 thrombosis (3 venous and 2 arterial: 1 pulmonary embolism, 1 cerebral vein thrombosis CVT, and 1 splanchnic thrombosis, 1 atrial thrombus and 1 acute myocardial infarction in the same APS patient experiencing CVT). Thrombosis was associated with the presence of secondary ES (p=0.03). Five patients are still receiving TPO-RA, whilst the other stopped because of persistent CR (N=12), thrombosis (N=3), increase in bone marrow reticulin fibrosis (N=1), or death for infectious complication. Conclusions: TPO-RAs were effective in more than 80% of ES patients, even heavily pre-treated. However, TPO-RA use was complicated by a high occurrence of thrombotic events that may be also favored by the underlying conditions. Additionally, TPO-RA required a concomitant therapy in the majority of patients, suggesting that in ES autoimmune platelet destruction cannot be completely overcome by bone marrow stimulation. Figure 1 Figure 1. Disclosures Patriarca: Incyte: Honoraria; Argenix: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Takeda: Honoraria. Glenthøj: Sanofi: Research Funding; Bristol Myers Squibb: Consultancy; Saniona: Research Funding; Agios: Consultancy; Novo Nordisk: Honoraria; Novartis: Consultancy; Alexion: Research Funding; Bluebird Bio: Consultancy. Lund Hansen: Alexion: Research Funding; Novartis: Research Funding. Frederiksen: Gilead: Research Funding; Alexion: Research Funding; Novartis: Research Funding; Janssen Pharmaceuticals: Research Funding; Abbvie: Research Funding. Gonzalez-Lopez: Sobi: Other: Advisory board honoraria; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Novartis: Other: Advisoryboard and speakers honoraria, Research Funding; Grifols: Other: Advisory board honoraria. Barcellini: Novartis: Honoraria; Agios: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees. Fattizzo: Kira: Speakers Bureau; Alexion: Speakers Bureau; Novartis: Speakers Bureau; Momenta: Honoraria, Speakers Bureau; Apellis: Speakers Bureau; Annexon: Consultancy; Amgen: Honoraria, Speakers Bureau. OffLabel Disclosure: Thrombopoietin receptor agonists in patients suffered from Evans syndrome when ITP is refractory/relapsing to standard therapies

scholarly journals Efficacy of Biofeedback Therapy in Clinical Practice for the Management of Chronic Constipation and Fecal Incontinence

2018 ◽  
Vol 2 (3) ◽  
pp. 126-131 ◽  
Author(s):  
Colleen H Parker ◽  
Stanley Henry ◽  
Louis W C Liu
Keyword(s):  
Clinical Practice ◽  
Fecal Incontinence ◽  
Chronic Constipation ◽  
Overall Response Rate ◽  
Response Rate ◽  
Response Rates ◽  
Symptom Improvement ◽  
Biofeedback Therapy ◽  
Dyssynergic Defecation ◽  
Overall Response

Abstract Background Chronic constipation (CC) and fecal incontinence (FI) are often secondary to pelvic floor neuromuscular sensory or motor dysfunction. Biofeedback therapy (BFT) uses visual and verbal feedback to improve anorectal coordination, strength and sensation. In clinical trials, BFT demonstrated response rates between 70% and 80%. The purpose of this study is to determine the effectiveness of BFT in clinical practice. Methods In this retrospective observational cohort study, the charts of all patients who completed BFT at our centre were reviewed. A positive response to BFT was defined as improvement in ARM profile from baseline or subjective symptom improvement or both. Descriptive statistics were used to analyze the data. Results One hundred thirty patients with an average age of 57.5 ± 16.4 years and 79.2% female were included. Of all patients, 43.1% were referred for CC, 37.7% for FI, 16.9% for alternating CC and FI, and 2.3% for rectal pain. The overall response rate to BFT was 76.2% (n=99). Of those that responded, 64.6% (n=64) demonstrated both ARM and symptom improvement, 27.3% (n=27) had ARM improvement but no symptom improvement, and 8.1% (n=8) had symptom improvement but no ARM improvement. In patients with FI, the overall response rate was 79.6% (n=39) with symptom improvement in 67.3% (n=33). In those with CC with dyssynergic defecation (n=53), the overall response rate was 69.8% (n=37); however, only 45.3% (n=24) had symptomatic improvement. Conclusion In our clinical practice, although overall response rates to BFT are similar to published reports, patients with CC with dyssynergic defecation are less likely to have symptomatic response compared with those with FI.

scholarly journals Randomized Double-Blind Clinical Trial Comparing Safety and Efficacy of the Biosimilar BCD-021 with Reference Bevacizumab

2021 ◽  
Author(s):  
Daniil Stroyakovskiy ◽  
Natalya Fadeeva ◽  
Marina Matrosova ◽  
Konstantin Shelepen ◽  
Grigoriy Adamchuk ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Response Rate ◽  
Response Rate ◽  
Response Rates ◽  
Phase Iii ◽  
Occurrence Rate ◽  
Study Endpoint ◽  
Primary Study ◽  
Overall Response ◽  
The Difference

Abstract Background BCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC). Methods Patients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%]. Results In total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n = 4; 1.96%) and comparator (n = 5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures. Conclusions Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug. Trial registration: The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).

Escalation Treatment Algorithm with Bortezomib, Dexamethasone and Bendamustine for Patients with Relapsed or Refractory Multiple Myeloma: A Singel Centre Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3540-3540 ◽  
Author(s):  
Roland Fenk ◽  
Mark Michael ◽  
Fabian Zohren ◽  
Thorsten Graef ◽  
Arkosch Czibere ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Overall Response Rate ◽  
Response Rate ◽  
Treatment Algorithm ◽  
Response Rates ◽  
Treatment Schedule ◽  
Prognostic Parameters ◽  
Minor Response ◽  
Overall Response

Abstract Bortezomib has improved the outcome of patients with multiple myeloma. Nevertheless, bortezomib monotherapy achieves responses in less than 50% of patients with advanced disease. Combination therapy can improve response rates but is associated with more adverse events such as neuropathy or myelosuppression. Therefore, we evaluated a step-wise escalation treatment algorithm for patients with relapsed or refractory myeloma. The initial treatment (step1) consisted of bortezomib monotherapy (1.3mg/m2 on day 1,4,8,11). Patients who did not show a at least 25% reduction of paraprotein at the beginning of cycle 2 received an escalated treatment (step2) with bortezomib and dexamethasone (40mg on day 1,4,8,11). The next treatment escalation (step3) was performed by addition of bendamustine (50–100mg/m2 on day 1 + 8) to bortezomib and dexamethasone. Step3 was used for patients who did respond with less than a minor response to one cycle of step2 treatment. We report on 48 patients who have been treated at our institution according to this regimen. Patients median age was 59 years with a median β2-microglobuline level of 3.8 g/dl and median albumine level of 3.7 g/dl. All patients were heavily pre-treated with in median three prior treatment regimen including high-dose therapy and thalidomide in more than 90% of patients. Escalation therapy was applied as planned to 36 (75%) patients, whereas 12 (25%) patients received step2 at the beginning of treatment due to physicians decision because of fulminant disease progression with hypercalcemia or severe tumor burden. Toxicity was as expected for bortezomib monotherapy and was manageable with escalated treatment steps. Response rates for patients in step1 were 11% nCR, 36% PR and 11% MR. In step2 (n=26) response rates were 31% PR, 15% MR and in step3 (n = 7) 43% PR and 29% MR. This results in an overall response rate of 80% for all patients. Patients with fulminant progressive disease who needed upfront treatment with step2 had an inferior overall response rate of 42% in comparison to 90% for patients who were treated according to the planned treatment schedule. With a median follow-up of 26 months the median time to progression and overall survival was 9 months and not reached for patients in the planned program and 2 and 4 months for the patients with upfront escalated therapy. Univariate analysis including several conventional prognostic parameters revealed physicians decision for upfront escalated treatment and age >60 years as the only bad prognostic factors. Interestingly, for patients within the planned treatment schedule, response to previous therapies, the extent of paraprotein reduction and the required escalation step had no impact on response duration. Another interesting observation of our single center study was that re-exposure of step3 treatment at the time of relapse (n=8) resulted in a new remission in 50% and in stable disease in 38% of patients. In conclusion, escalating therapy with bortezomib, dexamethasone and bendamustine induces durable remissions in the majority of patients, even in the presence of poor prognostic parameters. However, this treatment algorithm is not applicable for patients presenting with fulminant disease progression, as these patients need more aggressive regimens.

Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era

2020 ◽  
Vol 20 ◽  
Author(s):  
Giuseppe Lassandro ◽  
Valentina Palladino ◽  
Giovanni Carlo Del Vecchioa ◽  
Viviana Valeria Palmieri ◽  
Paola Carmela Corallo ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Treatment Options ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor ◽  
Related Quality ◽  
Health Related

Background and Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safety and effective for the treatment of pediatric ITP. The aim of our research is defining the role of thrombopoietin receptor agonists in the management of pediatric ITP. Method: This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in management of the disease. Results: Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. Conclusion: Although TPO-RAs long term efficacy and safety still require further investigations, their use is gradually expanding in clinical practice of children with ITP.

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