Long Term Efficacy and Safety Results and Analysis of Dose Correlations from the Phase I/II Peginvera Study of Ropeginterferon Alfa-2b, a Novel IFNa-2b, in Polycythemia Vera Patient

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4056-4056
Author(s):  
Heinz Gisslinger ◽  
Veronika Buxhofer-Ausch ◽  
Josef Thaler ◽  
Ernst Schlögl ◽  
Gunther Gastl ◽  
...  
Keyword(s):  
Research Funding ◽  
Dose Group ◽  
Low Dose ◽  
Term Treatment ◽  
High Dose ◽  
Individual Response ◽  
Molecular Response ◽  
Efficacy And Safety ◽  
Long Term Treatment

Abstract Background Ropeginterferon alfa-2b (AOP2014/P1101) is a novel long-acting pegylated IFN-alpha-2b, composed of mainly one isoform, resulting in longer half-life and exposure time. Reduced dosing frequencies, better tolerability, improved compliance and more favorable long-term treatment outcomes in patients with polycythemia vera (PV) are expected. The drug has Orphan designation by EMA and FDA and is currently in the phase III stage of development. Study design Efficacy and safety data are being collected in the follow-up extension stage of the study (collecting the data of both Phase I and Phase II portions of the study), after the maximum tolerated dose (MTD) of ropeginterferon alfa-2b, administered subcutaneously every 14 to 28 days, has been defined earlier. Patients with confirmed diagnosis of PV, age ≥18 years, both naïve and cytoreductively pre-treated were eligible. After establishing the MTD, an extended cohort of 25 additional patients has been planned to be recruited. Complete hematological response (CR) is defined by hematocrit (Hct)<45%, platelet count≤400*109/L, WBC count≤10*109/L, normal spleen size by sonography, and absence of thromboembolic events. Partial response (PR) is defined as Hct<45% without phlebotomy but with persistent splenomegaly or elevated (>400*109/L) platelet count, or reduction of phlebotomy requirements by at least 50%. Complete molecular response has been defined as reduction of any molecular abnormality to undetectable levels; partial molecular response as: reduction ≥ 50% in patients with < 50% mutant allele burden, or a reduction ≥ 25% in patients with > 50% mutant allele burden. The present analysis was focused on long-term tolerability and safety in correlation with the dose of ropeginterferon alfa-2b in PV. Results Data on treatment as by July, 24, 2015, are covered by the current analysis. Baseline characteristics of the study cohort during short-term treatment were already presented earlier (Gisslinger et al, ASH 2013). The full analysis set and efficacy set were composed of 51 and 47 patients, respectively. Currently, the median reported treatment duration is 138 weeks, 33 patients completed their follow up for two years, 19 for three years. Starting with the week 10, Hct-level, platelet- and WBC-counts could be constantly maintained within normal range in the majority of patients. In a group of patients with the mean administered dose of <300 µg ("low dose", n=36), CR as best individual response was achieved in 20 (56%) patients, and PR in 14 (39%) compared to the CR and PR in the high dose (>300 µg, n=11) group of 8 (73%) and 3 (27%) respectively. However, no statistical significance can be observed if correlation between the dose and response status was analyzed. 30 patients are still being treated in the study. Similarly, no association between the dose and occurrence of adverse events in the study could be observed. Complete molecular response as best individual response was observed more frequently in the high dose group 4 (36%) compared to 8 (23%) in the low dose group, while partial molecular responses were equally frequent in both dose groups (in 6/55% and 20/57%, respectively). 21 patients discontinued the study, 18 being treated with AOP2014 doses corresponding to low, and 3 to the high dose arms, corresponding to the drop-out rate of 50% and 27% in the respective arms. Interestingly, all discontinuations in the high dose group occurred within the first year of treatment (at weeks 16, 18 and 32), while the drop-outs in the low dose group (6 patients, 33%) discontinued the study after completion of their first year of treatment. Conclusions Efficacy and safety profile remain in line with expectations from other (pegylated) interferons. Overall response rate of >80% with cumulative CRs in 45-50%, accompanied by phlebotomy independence, normalization of hematological parameters and spleen size reduction in majority of patients have been observed. Significant and sustained JAK2 allelic burden decrease, starting from week 28 of treatment, was seen. No significant difference between the two mean dose levels regarding response rates or adverse events even during long-term treatment and observation could be observed. These finding are to be further verified in a larger prospective setting. Disclosures Gisslinger: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Geron: Consultancy; Sanofi Aventis: Consultancy; Janssen Cilag: Honoraria, Speakers Bureau. Buxhofer-Ausch:AOP Orphan: Research Funding. Thaler:AOP Orphan: Research Funding. Schlögl:AOP Orphan: Research Funding. Gastl:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP Orphan: Research Funding. Ban:AOP Orphan: Research Funding. Egle:AOP Orphan: Research Funding. Melchardt:AOP Orphan: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Willenbacher:COMET Center ONCOTYROL: Research Funding; AOP Orphan: Research Funding. Kralovics:AOP Orphan: Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees. Zörer:AOP Orphan: Employment. Ammann-Mwathi:AOP Orphan: Employment. Kadlecova:AOP Orphan: Consultancy. Zagrijtschuk:AOP Orphan: Employment. Klade:AOP Orphan: Employment. Greil:Pfizer: Honoraria, Research Funding; GSK: Research Funding; Boehringer-Ingelheim: Honoraria; AOP Orphan: Research Funding; Celgene: Consultancy; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; Astra-Zeneca: Honoraria; Amgen: Honoraria, Research Funding; Ratiopharm: Research Funding; Sanofi Aventis: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Roche, Celgene: Honoraria, Research Funding.

Long-Term Treatment and Tolerability of the Novel Proteasome Inhibitor Carfilzomib (CFZ) In Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1953-1953 ◽  
Author(s):  
Sundar Jagannath ◽  
Ravi Vij ◽  
Jonathan L. Kaufman ◽  
Thomas Martin ◽  
Ruben Niesvizky ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Proteasome Inhibitor ◽  
Research Funding ◽  
Low Dose ◽  
Single Agent ◽  
Term Treatment ◽  
Extension Study ◽  
Advisory Committees ◽  
Long Term Treatment

Abstract Abstract 1953 Background: Carfilzomib (CFZ) is a novel, selective proteasome inhibitor that differs from BTZ both structurally and mechanistically. CFZ overcomes BTZ-resistance in vitro, lacks the off-target activities of BTZ in preclinical studies, and does not cause neurotoxicity in long-term (6–9 month) chronic animal toxicology studies. Single-agent CFZ produces durable responses in relapsed and relapsed/refractory (R/R) multiple myeloma (MM) without dose-limiting PN, and can be given to pts with substantial renal dysfunction. Here we report on the clinical experience with long-term treatment (>12 cycles, >11 months) with single-agent CFZ in pts with MM. Methods: Included in the present analysis were pts with MM who initially enrolled in studies PX-171-002 (Phase 1), PX-171-003 (relapsed and refractory MM), PX-171-004 relapsed following 1–3 therapies), and PX-171-005 (relapsed and refractory MM with varying degrees of renal dysfunction). The majority of pts initially received CFZ at 20 mg/m2 IV, on Days 1, 2, 8, 9, 15, and 16 in a 28-day cycle (C). In some trials, the dose was escalated following cycle 1 to 27 mg/m2 for up to 12 C. Recently, higher doses including 36 and 45 mg/m2 have been successfully attempted using a 30-min infusion. Pts who completed their full course of CFZ therapy on a given trial were given the option to enter the PX-171-010 extension study. In this extension study, CFZ was initially administered at the same dose-level and frequency as given in the last cycle of the pts’ previous CFZ study. CFZ could be administered at a reduced frequency of twice weekly every other week at the discretion of the investigator and pts could continue treatment until disease progression or unacceptable toxicity. Results: More than 10% of pts in studies PX-171-003 and PX-171-005, and approximately 24% of pts in PX-171-004 completed 12 cycles of induction therapy with CFZ (QDx2 weekly for 3 of 4 weeks). As of 31 July 2010, 42 of the pts completing 12 cycles of CFZ in a previous study either enrolled in PX-171-010 (N=38) or were treated on single-patient INDs prior to the availability of PX-171-010 (N=4). CFZ was administered as either a single agent (N=38) or combined with low-dose dexamethasone (N=4, all in PX-171-005). Twenty-five of the 42 MM pts (60%) remain on treatment: 24 receiving single agent CFZ at 27 mg/m2 (range 15–45 mg/m2) and 1 receiving CFZ + low dose dexamethasone. The median duration of CFZ treatment in this cohort is 14 months. The longest period of treatment is >27 months, and 12 pts have completed over 18 months of total continuous CFZ dosing. Of the 17 MM pts who discontinued therapy, 16 did so due to progressive disease and one pt had pneumonia, stopped therapy, and elected not to restart treatment. Cumulative toxicities were not observed, and AEs were similar to those reported in other studies of single-agent CFZ. There were 7 serious adverse events (SAEs, 1 patient each) reported in the extension study: 4 were possibly related and included infection, dyspnea, bronchitis and asthenia. Doses were interrupted and restarted or maintained for all of the pts with possibly related SAEs. Peripheral neuropathy and significant renal dysfunction were not observed with in this extension trial. Conclusions: CFZ is a highly selective proteasome inhibitor that can be administered to pts with MM for prolonged periods with no apparent cumulative toxicities. Disease control is possible with this single-agent treatment, even though many of the pts had disease that was refractory to multi-agent therapy prior to entering their initial CFZ trial. Following 12 cycles (11 months) of induction therapy (QDx2 weekly for 3 of 4 weeks) maintenance CFZ sustained disease control and provided excellent long-term tolerability, with the option for pts to switch to twice weekly dosing every other week. Disclosures: Jagannath: Celgene: Honoraria; Millenium/Takeda Pharma: Honoraria; J&J Family: Honoraria; Onyx: Honoraria; Merck: Honoraria. Vij:Onyx: Honoraria. Kaufman:Celgene, Millenium: Consultancy; Celgene, Merck: Research Funding. Martin:Celgene: Honoraria; Onyx: Consultancy. Niesvizky:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding. Gabrail:Millenium: Research Funding. Alsina:Millenium: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy. Wong:Onyx Pharmaceuticals: Employment. Le:Onyx Pharmaceuticals: Employment. McCulloch:Onyx Pharmaceuticals: Employment. Hannah:Onyx Pharmaceuticals: Consultancy. Kauffman:Onyx Pharmaceuticals: Employment. Siegel:Millenium: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals The efficacy and safety of high-dose verapamil and diltiazem in the long-term treatment of stable exertional angina

1984 ◽  
Vol 7 (12) ◽  
pp. 648-653 ◽  
Author(s):  
D. A. Weiner ◽  
C. H. Mccabe ◽  
S. S. Cutler ◽  
T. J. Ryan ◽  
M. D. Klein
Keyword(s):  
Term Treatment ◽  
High Dose ◽  
Efficacy And Safety ◽  
Long Term Treatment ◽  
Exertional Angina

scholarly journals Long-Term Efficacy and Safety of Low-Molecular-Weight Heparins (LMWH) for Cancer-Associated Venous Thromboembolism (VTE) in Tropique, a Prospective Non-Interventional Observational Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4273-4273 ◽  
Author(s):  
Dominique Farge ◽  
Philippe Debourdeau ◽  
Norbert Claude Gorin ◽  
Anne Lamblin ◽  
Francis Cajfinger
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Term Treatment ◽  
Efficacy And Safety ◽  
Patients With Cancer ◽  
Recommended Treatment ◽  
Long Term Treatment ◽  
History Of ◽  
Antineoplastic Treatment

Abstract Introduction Long-term treatment with LMWH is the standard therapy for patients with cancer-associated VTE. Recommended treatment regimen include the prescription of LMWH at treatment doses according to approved administration schedule for at least 3 months in the absence of severe renal insufficiency (CrCl<30 mL/min) [1, 2]. The TROPIQUE study documented the prescription and use of long-term treatment with LMWH in cancer patients. Here we report the findings on the secondary outcomes, clinical efficacy and safety. Methods Adult patients with cancer-associated VTE receiving antineoplastic treatment or palliative care were eligible to participate. Efficacy outcomes measures were VTE recurrence including deep-vein thrombosis (DVT) and pulmonary embolism (PE), visceral thrombosis and central venous catheter (CVC)-associated thrombosis. Safety outcomes included all and major bleeding according to ISTH definition [3], thrombocytopenia and deaths. Incidences of 7% of VTE recurrence and 6% of major bleeding were expected. With a sample of 384 patients, the rate of VTE recurrence and major bleeding would be detected with a precision of ±2.6% and ±2.4%, respectively, with a 95% confidence interval. A total of 400 patients were therefore planned to be included in the study. Results A total of 409 patients with symptomatic cancer-associated VTE (Table 1) aged 65±12.1 years of whom 49.9% female were consecutively included from November 2012 to August 2013. A history of previous VTE was found in 54 (13.2%), surgery or trauma in 100 (24.4%), CVC in 303 (74.1%) and an immobilization over 1 month in 47 (11.5%) patients, respectively. At study inclusion, 30 (7.3%) patients had platelet count ≤ 100 x109/L, and 129 (31.5%) had reported anemia while 16 (3.9%) patients had a history of bleeding in the last month. At baseline, more than 80% of patients presented with at least a PE or a lower-limb DVT of s. Table 1 VTE diagnosis at baseline (patients at least with one of the following) VTE diagnosis (at least one of the following) n (%) PE 145 (35.5) DVT lower limb 193 (47.2) Proximal 107 (56.0) Distal 72 (37.7) DVT upper limb 45 (11.0) Visceral thrombosis 16 (3.9) CVC-associated thrombosis 66 (16.1) Mean treatment duration was 5.28 ± 2.07 months. As the majority of patients were treated with tinzaparin (73.6%), clinical outcomes are therefore presented for tinzaparin, other LMWH and all LMWH (Table 2). A total of 21 events of VTE recurrence occurred in 19 patients during the overall study period, with a Kaplan-Meir estimate of the probability of VTE recurrence at 6 months of 6.1%. Table 2 Outcomes in patients with cancer-associated VTE treated with long-term LMWH [n (%)]. Patients treated Tinzaparin n=301 Other LMWH n=108 All LMWH n=409 Patients documented n=292 n=100 n=392 Patients with at least 14 (4.8) 5 (5) 19 (4.8)  one VTE recurrence - - - Events (2 patients had 3 4 7  more than one event) 5 1 6 DVT 0 1 1 PE 6 1 7 Visceral thrombosis CVC-associated thrombosis Bleeding n=292 n=100 n=392 All 44 (15.1) 11 (11.0) 55 (14.0) Major 16 (5.5) 7 (7.0) 23 (5.9) Thrombocytopenia n=290 n=100 n=390  (n platelets/mm3) 53 (18.3) 15 (15.0) 68 (17.4) All n=65 n=17 n=82 < 50,000 22 5 27 Drop > 50% 15 2 17 Deaths n=301 n=107 n=408 All 102 (33.9) 44 (41.1) 146 (35.8) Cause of death* n=100 n=44 n=144 LMWH treatment** 1# 0 1## Cancer 87 39 126 Sepsis 4 1 5 Bleeding 4 1 5 Antineoplastic treatment 1 0 1 PE 0 1 1 Other 7 3 10 *Multiple causes of death may have been reported in the same patient; **fatal bleeding reported as LMWH-related; #n=99; ## n=143 Kaplan-Meier estimate of the probability of bleeding at 6 months was 15.9% while corresponding estimates were 18.1% for thrombocytopenia and 34.5% for deaths. Of the five (3.5%) patients who reported fatal bleedings one was reported as related to the LMWH treatment. No heparin-induced thrombocytopenia was reported in the study. Conclusion Clinical outcomes were consistent with previous observations in this patient population except a lower incidence of VTE recurrence compared with previous studies. Study results tend to confirm the favorable efficacy and safety profile of LMWH for the long-term treatment of patients with cancer-associated VTE, when used according to recommended treatment duration and respecting contra-indications. Schulman. J Throm Haemost. 2005 Apr;3(4):692-4.Farge J Thromb Haemost. 2013 Jan;11(1):56-70.Debourdeau P, J Thromb Haemost. 2013 Jan;11(1):71-80 Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.

Local ultra-low-dose estriol gel treatment of vulvo-vaginal atrophy: efficacy and safety of long-term treatment

2019 ◽  
Vol 36 (6) ◽  
pp. 535-539
Author(s):  
Paola Villa ◽  
Valeria Tagliaferri ◽  
Inbal Dona Amar ◽  
Clelia Cipolla ◽  
Fabio Ingravalle ◽  
...  
Keyword(s):  
Low Dose ◽  
Term Treatment ◽  
Vaginal Atrophy ◽  
Efficacy And Safety ◽  
Long Term Treatment ◽  
Gel Treatment

Efficacy and Safety of Deferasirox (Exjade®) in Patients with β-Thalassemia Major Treated for up to 5 Years.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4063-4063 ◽  
Author(s):  
M. Domenica Cappellini ◽  
Silverio Perrotta ◽  
Leyla Agaoglu ◽  
Yesim Aydinok ◽  
Marcello Capra ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Iron Concentration ◽  
Term Treatment ◽  
Efficacy And Safety ◽  
Advisory Committees ◽  
Absolute Change ◽  
Transfusion Requirements ◽  
Long Term Treatment

Abstract Abstract 4063 Poster Board III-998 Background In a large, 1-yr Phase 3 clinical trial, patients (pts) with β-thalassemia (aged ≥2 yrs) were randomized to receive deferasirox (Exjade®) or deferoxamine (DFO), with doses assigned according to baseline liver iron concentration (LIC). Pts completing the 1-yr core were permitted to enter a 4-yr extension; those receiving deferasirox continued on this therapy (deferasirox cohort), while those receiving DFO crossed over to deferasirox (crossover cohort). This analysis evaluates the efficacy and safety of deferasirox over 5 yrs. Methods Based on analyses showing that iron burden and transfusional iron intake need to be considered for appropriate dosing of deferasirox, dose adjustments were permitted in the extension to ensure optimal dosing. Deferasirox dose in the extension was initially based on dose response in the core (deferasirox cohort only) and end-of-core LIC (biopsy or SQUID); subsequent adjustments in steps of 5–10 mg/kg/day were based on serum ferritin (SF) levels and safety markers. Efficacy was assessed by monthly SF levels and LIC at baseline, end of 1-year core and end of study (EOS) (or upon discontinuation). Safety was assessed by incidence and type of adverse events (AEs) and changes in laboratory parameters. Results 296 pts (deferasirox cohort) and 259 pts (crossover cohort) received ≥1 dose of deferasirox; 181 (61%) & 190 (73%) pts from each cohort respectively completed the extension. Most common reasons for discontinuation: consent withdrawal (n=62) and AEs (n=43). Most common AEs leading to discontinuation: increased ALT [n=5], increased transaminases [n=4], glycosuria [n=4]. 2 deaths occurred during the extension in the deferasirox cohort (cardiac failure, cardiomyopathy); 2 in the crossover cohort (cardio-respiratory arrest, road traffic accident); none considered to be related to study drug. Median duration of deferasirox treatment was 61.2 & 48.1 mths in deferasirox & crossover cohorts, respectively. At start of deferasirox, mean LIC was 14.0 ± 9.8 & 10.4 ± 7.6 mg Fe/g dry weight (dw) and median SF was 2211 & 1758 ng/mL in deferasirox and crossover cohorts, respectively. Transfusion requirements at start of deferasirox were comparable; most pts (81% & 83%, respectively) receiving 7–14 mL/kg/mth. Mean deferasirox dose during study: 21.6 ± 6.4 & 23.2 ± 5.9 mg/kg/d (final actual dose: 24.4 ± 8.7 & 27.0 ± 8.0 mg/kg/d) in deferasirox and crossover groups, respectively. Most pts were receiving 15–<35 mg/kg/day at EOS (75% & 78%, respectively); 11% & 17% were receiving ≥35 mg/kg/day. In pts who received at least 5 yrs of deferasirox and at least 4 yrs in the crossover group, mean absolute change in LIC were –5.3 ± 10.1 mg Fe/g dw (n=173; P<0.001) & –2.4 ± 7.6 mg Fe/g dw (n=99; P<0.001) and median absolute change in SF were –775 ng/mL (range: –10164–2572; n=182; P<0.001) & –371 ng/mL (range: –4498–2636; n=151; P<0.001), respectively (Figure). Percentage of pts with LIC<7 mg Fe/g dw increased from 35% to 45% & SF≤1000 ng/mL increased from 12% to 33% from the start of deferasirox to EOS (LIC: EOS, last available value; SF: EOS, average of at most 3 available values after start of deferasirox). Most common drug-related AEs (≥5% overall) after start of deferasirox in deferasirox & crossover cohort, respectively: increased blood creatinine (n=42, 14%; n=20, 8%), nausea (n=28, 10%; n=13, 5%), vomiting (n=18, 6%; n=17, 7%), diarrhea (n=13, 4%; n=15, 6%) & rash (n=17, 6%; n=19, 7%). Frequency of drug-related AEs decreased from year to year. In deferasirox & crossover cohorts, 26 (9%) & 11 (4%) pts had 2 consecutive serum creatinine increases >33% above baseline & upper limit of normal (ULN) & 3 (1%) & 2 (1%) pts had ALT >10 x ULN on 2 consecutive visits, respectively, after start of deferasirox. Conclusions Long-term treatment with deferasirox (for up to 5 yrs) significantly decreased iron burden in β-thalassemia pts aged ≥2 yrs with an increasing percentage of pts achieving therapeutic goals of LIC<7 mg Fe/g dw and SF≤1000 ng/mL. Significant improvements in LIC and SF were also observed after switching from DFO. Deferasirox was well tolerated over this long-term treatment, and the frequency of AEs decreased over time. Disclosures: Cappellini: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genzyme: Membership on an entity's Board of Directors or advisory committees. Perrotta:Novartis: Consultancy, Research Funding. Aydinok:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Membership on an entity's Board of Directors or advisory committees. Piga:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Griffel:Novartis Pharmaceuticals: Employment, Equity Ownership. Lagrone:Novartis Pharmaceuticals: Employment. Clark:Novartis Pharma AG: Employment. Kattamis:Novartis: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Experience with Low-Dose Sodium Valproate in Idiopathic Generalized Epilepsy Patients: A Long-Term Follow-Up Study on Selective Cohort from North India

2021 ◽  
Vol 12 (01) ◽  
pp. 046-050
Author(s):  
Deepak Goel ◽  
Manish Mittal
Keyword(s):  
Low Dose ◽  
Term Treatment ◽  
North India ◽  
High Dose ◽  
Idiopathic Generalized Epilepsy ◽  
Number Of Patients ◽  
Long Term Treatment ◽  
Generalized Epilepsy

Abstract Background Idiopathic generalized epilepsy (IGE) is found in 20 to 30% of all patients presenting with seizures. Most of the patients require lifelong drug treatment. Efficacy and tolerability are important issues while selecting the most appropriate drug for a person with IGE. Objective The aim of this study was to look for usefulness of small dose valproate (<1,000 mg/day) in long-term treatment of IGE patients. Methods Diagnosis of IGE made with standard criteria among all patients presenting with seizures. Patients put on full doses of valproate (>1,000 mg/day) in first year, then reduction started in next year in patients with full seizure remission, and finally maintained on lowest possible dose of valproate. Lowest dose was defined as the minimum dose without seizures (between 200 and 900 mg/day). Patients, who were refractory on monotherapy, were put on add-on drug and followed for remission and reduction in doses of valproate at minimum possible dose. Results IGE was diagnosed in 21% of all patients presenting with seizures. Among 420 patients of IGE 368 (87.5%) were started on high-dose valproate monotherapy, 155 (42.1%) were responsive to single drug while 213 (57.9%) had been given add-on drug either lamotrigine or clonazepam or both. After minimum 3-year follow-up, 298 (81%) could be managed on low-dose valproate (<1,000 mg) without any relapse during 12 to 80 months follow-up. Conclusion Significant number of patients with IGE can be managed on low-dose valproate with good seizure control and less side effects.

Efficacy and safety of long-term treatment with low-dose rituximab for relapsing mixed cryoglobulinemia vasculitis

2017 ◽  
Vol 36 (3) ◽  
pp. 617-623 ◽  
Author(s):  
Stefania Colantuono ◽  
Milica Mitrevski ◽  
Baoran Yang ◽  
Julia Tola ◽  
Maurizio Carlesimo ◽  
...  
Keyword(s):  
Low Dose ◽  
Mixed Cryoglobulinemia ◽  
Term Treatment ◽  
Efficacy And Safety ◽  
Long Term Treatment

scholarly journals Thromboembolic Risk Reduction and High Rate of Complete Molecular Response with Long-Term Use of Ropeginterferon Alpha-2b in Polycythemia Vera: Results from a Randomized Controlled Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 553-553 ◽  
Author(s):  
Jean-Jacques Kiladjian ◽  
Christoph Klade ◽  
Pencho Georgiev ◽  
Dorota Krochmalczyk ◽  
Liana Gercheva-Kyuchukova ◽  
...  
Keyword(s):  
Adverse Events ◽  
Research Funding ◽  
Term Treatment ◽  
Control Group ◽  
Molecular Response ◽  
Allele Burden ◽  
Long Term Treatment ◽  
Jak2v617f Allele Burden ◽  
Complete Molecular Response

Introduction: The key treatment goals for polycythemia vera (PV) are to prevent thromboembolic events and minimize the risk of progression, ultimately modifying the natural history of the disease by selectively targeting the malignant clone. In the PROUD-PV/CONTINUATION-PV study, long-term treatment with ropeginterferon alpha-2b (BESREMi®; hereafter ropeg) was compared with standard cytoreductive therapy regarding thromboembolic and other adverse events as well as hematological and molecular parameters over a four-year period. Methods: Cytoreduction-naïve or HU-pre-treated patients aged ≥18 years diagnosed with PV according to WHO 2008 criteria were eligible. A total of 257 patients were randomly allocated to ropeg or hydroxyurea at individualized doses for 12 months in the initial study phase (PROUD-PV). In the ongoing extension phase (CONTINUATION-PV), patients in the hydroxyurea arm were permitted to switch to best available treatment. Efficacy assessments included a longitudinal analysis of complete hematological response (CHR) and complete molecular response (CMR; JAK2V617F was determined using real-time PCR [ipsogen® JAK2 MutaQuant® kit; QIAGEN GmbH]), defined by modified ELN criteria. Discontinued patients were considered non-responders. A data snapshot was performed once all patients reached 48 months of treatment; all available safety data were included. Results: Ninety-five patients in the ropeg arm and 76 in the control arm entered the extension phase. At the time of analysis 139 patients remained on study: 74/95 in the ropeg arm and 65/76 in the control arm. Almost all patients in the control arm (&gt;97% at the last available assessment) continued on HU. The rate of patients in CHR was significantly higher in the ropeg arm than in the control arm in the 4th year (60.6% versus 43.4%; p=0.02), as seen after 2 and 3 years of treatment. In line with this effective control of hematologic parameters by ropeg, a very low rate of major thromboembolic adverse events was observed in the ropeg arm: 0.0%, 0.0% and 1.1% of patients in the 2nd, 3rd and 4th years, respectively. In the control arm, rates of major thromboembolic adverse events in the 2nd, 3rd and 4th year were 0.9%, 1.4% and 0.0%, respectively. The median JAK2V617F allele burden declined from 37.3% at baseline to 9.8% over 4 years in the ropeg arm, whereas in the control group, the median allele burden increased from 38.1% to 43.1% in the same period (p&lt;0.0001). The rate of molecular response (partial or complete) at 48 months was significantly higher among ropeg-treated patients than in the control arm (67.0% versus 25.7%; RR: 2.5 [95% CI: 1.7 to 3.7; p&lt;0.0001]). No patients achieved CMR in the control arm. In the ropeg arm, 13 patients had a JAK2V617F allele burden below the threshold of 1% at month 48, 11 of whom also had a CHR at this time point. An additional 34 patients in the ropeg arm achieved an allele burden &lt;10% at 48 months, suggesting that further patients may reach the &lt;1% threshold with ongoing treatment. In terms of safety, no new signals were detected in the 4th year. Rates of patients with treatment-related adverse events remained similar in the ropeg and control arms in the 4th year (ropeg: 28.7% of patients; control: 22.9%). Disease or treatment-related secondary malignancies reported in the entire study period comprised 2 cases of acute leukemia, 2 cases of basal cell carcinoma and 1 case of malignant melanoma, all in the control group; 1 case of disease-related transformation to myelofibrosis occurred in each treatment arm. Conclusions: Ropeg minimizes the occurrence of thromboembolic events in patients with PV over long-term treatment, without leukemogenic risk. In addition, we show for the first time in a randomized study that, in contrast to hydroxyurea, long-term ropeg treatment is capable of inducing deep molecular responses including CMR, which underscores its disease modifying potential. These results also suggest that selected patients could achieve operational cure (with both CHR and CMR) with ropeg, opening the way for treatment discontinuation. Disclosures Kiladjian: Novartis: Honoraria, Research Funding; AOP Orphan: Honoraria, Research Funding; Celgene: Consultancy. Klade:AOP Orphan Pharmaceuticals AG: Employment. Illés:Takeda, Seattle: Research Funding; Janssen, Celgene, Novartis, Takeda, Roche, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mayer:AOP Orphan Pharmaceuticals AG: Research Funding. Krejcy:AOP Orphan Pharmaceuticals AG: Employment. Hasselbalch:Novartis: Research Funding; AOP Orphan Pharmaceuticals: Other: Data monitoring board. Kralovics:Pharma Essentia: Honoraria; MyeloPro Diagnostics and Research: Equity Ownership; AOP Orphan Pharmaceuticals AG: Honoraria, Other: Advisory board; Qiagen: Honoraria; Novartis: Honoraria. Gisslinger:Celgene GmbH: Honoraria; Pharma Essentia: Other: Personal fees; Roche Austria GmbH: Consultancy; Janssen-Cilag: Honoraria; Novartis Pharma GmbH: Consultancy, Honoraria, Research Funding; AOP Orphan Pharmaceuticals: Consultancy, Honoraria, Research Funding; Myelopro GmbH: Consultancy.

Efficacy and safety of long-term treatment with monthly calcifediol soft capsules in vitamin D deficient patients

2021 ◽  
Author(s):  
Jódar Esteban ◽  
Jose Luis Perez-Castrillon ◽  
Dueñas Antonio ◽  
Gonzalo Hernandez ◽  
Nieves Fernandez ◽  
...  
Keyword(s):  
Vitamin D ◽  
Term Treatment ◽  
Efficacy And Safety ◽  
Long Term Treatment
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