Long-Term Dosing of AMG 531 in Thrombocytopenic Patients with Immune Thrombocytopenic Purpura: 48-Week Update.

Abstract AMG 531 is a novel thrombopoiesis-stimulating peptibody that increases platelet production by targeting the TPO receptor. The study described here is an ongoing, open-label extension assessing the safety and efficacy of long-term, weekly, subcutaneous administration of AMG 531 in ITP patients who have completed a previous AMG 531 study. Patients previously treated with AMG 531 receive the same starting dose as the final dose given in the previous study; placebo-treated patients begin the extension with a 1 μg/kg dose. Doses may be skipped, decreased, maintained, or increased based on platelet response. Patients who achieve a stable dose for at least 3 weeks (later amended to 4 weeks) may be allowed to self-administer the drug. A total of 104 patients have been enrolled; the longest AMG 531 treatment duration is 96 weeks. This planned interim analysis includes 36 patients (safety subset) whose previous study was a phase 2 trial. Data for patients previously enrolled in a phase 3 trial are still blinded. The 25 women and 11 men have a mean age of 50±13 (SD) years; 30 (83%) have had a splenectomy. Twelve patients entered the study using concurrent corticosteroids, which were tapered when the platelet count was >50x109/L. Adverse event (AE) profiles were similar for the intervals of weeks 1–24 vs 25–48 and beyond. The most frequent were headache (incidence of 2.0 per 100 weeks of subject exposure for weeks 1–24 vs 1.7 for weeks 25–48), upper respiratory infection (1.3 vs 0.8), and fatigue (0.9 vs 1.0). Four patients had serious treatment-related AEs: vaginal hemorrhage/anemia (withdrawn from treatment), diffuse reticulin formation in the bone marrow (withdrawn), bone pain (continues on treatment), and transverse sinus thrombosis with papilledema and temporary decrease in visual acuity (64-year-old patient with diabetes mellitus and a platelet count of 293x109/L at the time of the AE; this patient continues on treatment). No neutralizing antibodies have been detected to date. The efficacy subset consists of 27 patients who completed week 48 or beyond. Both the mean platelet count and the mean dose of AMG 531 have remained stable between weeks 24–48. The mean platelet count was 100x109/L ± 4.4 (SE) during weeks 1–24 and 131x109/L ± 5.3 (SE) during weeks 25–48. Eleven patients (41%) have had at least one platelet count >450x109/L, excluding counts associated with ITP rescue medication. Six of 12 patients were able to discontinue concurrent corticosteroids, and 2 had a >25% dose reduction. Individualized weekly doses of AMG 531 provide a therapeutic option for ITP. Most patients have been able to maintain a safe platelet count and to decrease or discontinue concurrent corticosteroid therapy.

Download Full-text

Long-Term Dosing of AMG 531 Is Effective and Well Tolerated in Thrombocytopenic Patients with Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v106.11.220.220 ◽

2005 ◽

Vol 106 (11) ◽

pp. 220-220 ◽

Cited By ~ 8

Author(s):

James B. Bussel ◽

David J. Kuter ◽

James N. George ◽

Louis M. Aledort ◽

Alan E. Lichtin ◽

...

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Neutralizing Antibodies ◽

Therapeutic Option ◽

Platelet Response ◽

Open Label ◽

Baseline Platelet Count ◽

First Response ◽

The Mean

Abstract AMG 531 is a novel platelet-stimulating peptibody that targets the TPO receptor, resulting in increased production of platelets. This ongoing, open-label study assessed the safety and efficacy of long-term AMG 531 dosing in ITP patients. Eligible patients have completed a previous AMG 531 study in ITP, are ≥18 years of age, have a baseline platelet count ≤50 x 109/L, with no recent significant change in medical history. The AMG 531 starting dose is 1μg/kg by SC injection with dose adjustment to an original maximum of 30μg/kg, since reduced to 15μg/kg. Patients are treated weekly unless the platelet count is >400x109/L. Concurrent corticosteroids can be tapered when the platelet count is ≥50x109/L. Preliminary data are available for 26 patients treated for up to 24 weeks: 17 women and 9 men; mean age, 48.4±11.6 (SD) years; mean baseline platelet count, 18.5±12.3 (SD) x109/L. Twenty-one patients (80.8%) had undergone a splenectomy before study entry; 6 (23.1%) were receiving concurrent corticosteroids for ITP. Twenty-one of 26 patients (80.8%) had a protocol-defined platelet response to AMG 531 (doubling of the baseline platelet count and ≥50x109/L). The mean AMG 531 dose at the first response was 3.7±2.7 (SD) μg/kg (at median 5 weeks); the mean dose at week 24 was 7.2±4.2 (SD) μg/kg. Twelve of 26 patients (46.2%) had a durable platelet response (doubling of the baseline count and ≥50x109/L at 6 or more of weeks 17–24). Twenty patients (76.9%) had a platelet count ≥100x109/L at least once; 7 (26.9%) had a platelet count ≥400x109/L. Of 6 patients on concurrent corticosteroids, 3 discontinued treatment and 2 had a ≥25% dose reduction. At least 1 serious adverse event was reported in 4 patients: anal fistula (unrelated to treatment), adverse drug reaction (unrelated), multiple sclerosis relapse (unrelated), bone pain (related), and diffuse reticulin formation in the bone marrow reported as myelofibrosis (related). Reticulin formation is hypothesized as due to excessive accumulation of megakaryocytes in the bone marrow. AMG 531 was discontinued, and a bone marrow 3 months later showed improvement. One patient experienced adverse events (musculoskeletal pain and headache) resulting in withdrawal from the study. No neutralizing antibodies have been detected to date. In summary, repeated exposure to AMG 531 has been generally well tolerated in this ongoing study. A total 80.8% of patients achieved a platelet response, defined as doubling of the baseline count and ≥50x109/L. Individualized weekly doses of AMG 531 may provide a therapeutic option in ITP, potentially enabling patients to taper off long-term corticosteroid therapy.

Download Full-text

Long-Term Dosing of AMG 531 in Thrombocytopenic Patients with Immune Thrombocytopenic Purpura: 2-Year Update.

Blood ◽

10.1182/blood.v110.11.568.568 ◽

2007 ◽

Vol 110 (11) ◽

pp. 568-568 ◽

Cited By ~ 2

Author(s):

James B. Bussel ◽

D.J. Kuter ◽

J.Th.M de Wolf ◽

T.H. Guthrie ◽

A. Newland ◽

...

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Neutralizing Antibodies ◽

Drug Exposure ◽

Therapeutic Option ◽

Platelet Response ◽

Initial Report ◽

Chronic Itp ◽

Long Term Treatment

Abstract AMG 531, a novel thrombopoiesis-stimulating peptibody, increases platelet production by stimulating the TPO receptor. This study is an ongoing, open-label extension assessing the safety and efficacy of long-term, weekly, SC administration of AMG 531 in patients with chronic ITP who completed a previous AMG 531 study. Patients previously treated with AMG 531 received the same starting dose as the final dose given in the previous study; placebo-treated patients began the extension at 1μg/kg. Doses could be adjusted based on platelet response. As of an April 2007 analysis, 137 patients were enrolled and 136 had received AMG 531. The longest treatment duration was 122 weeks; 22 patients were followed for 96 weeks or longer. At baseline, 91 women and 46 men had a mean age of 53±15(SD) years and a median (range) platelet count of 18(1–50)x109/L; 82 patients (60%) had undergone splenectomy. The most frequently reported adverse events (AEs) were headache (overall incidence 31%), contusion (27%), fatigue (24%), diarrhea (24%), epistaxis (23%), nasopharyngitis (21%), and arthralgia (20%). Exposure-adjusted analysis showed no trend for AEs to increase in frequency with increased drug exposure (table). Eleven patients had serious AEs judged by investigators as treatment-related including 3 withdrawn from study (vaginal hemorrhage, increased reticulin in the bone marrow reported as myelofibrosis, and initial report of multiple myeloma later reclassified as monoclonal gammopathy of undetermined significance - 1 report each) and 8 who continued on-study (bone marrow disorder/reticulin fibrosis - 3, unacceptably high platelet count - 2, thrombosis - 2, and cerebral thrombosis/papilloedema/temporary blindness - 1). One patient developed neutralizing antibodies to AMG 531 (absent on retesting 4 months after drug cessation), with no clinical sequelae and no cross-reactive antibodies to TPO. Overall, 112 patients (82%) achieved a platelet response (≥50x109/L and doubling of baseline). From week 4 onward, weekly incidence of platelet response ranged from 52–73% (figure). Median number of weeks to first response was 2 (median dose 3μg/kg). Of 30 patients with baseline use of concurrent ITP therapies, 13 were able to discontinue them and 6 additional patients had a >25% dose reduction. Individualized weekly doses of AMG 531 provide a therapeutic option for long-term treatment of chronic ITP. The safety profile has been acceptable, and most patients have been able to maintain a platelet response and discontinue or reduce concurrent ITP therapies. Exposure-Adjusted incidence of AEs with Overall Incidence ≥ 20% Platelet Response (≥ 50x109/L and Doubling of Baseline) by Study Week Platelet Response (≥ 50x109/L and Doubling of Baseline) by Study Week

Download Full-text

A case report of long-term complete remission following cessation of romiplostim dosing in a previously severe ITP patient.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e17001 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e17001-e17001

Author(s):

Allison Ashley Baxley ◽

James N George ◽

Deirdra Terrell ◽

Meredith Moorman ◽

Jennifer L. Holter

Keyword(s):

Clinical Trial ◽

Platelet Count ◽

Case Report ◽

Bleeding Complications ◽

Drug Discontinuation ◽

High Dose ◽

Platelet Response ◽

Open Label ◽

Platelet Production

e17001 Background: Primary Immune thrombocytopenia(ITP) is a chronic autoimmune disorder characterized by low platelet counts and bleeding complications. Platelet destruction together with insufficient platelet production occur through an antibody-mediated process and early treatment options revolve around targeting antibodies and immunologic pathways. Such therapies may not produce long-term responses and may be accompanied by considerable adverse effects which can lead to complications and/or drug discontinuation. Romiplostim is a thrombopoietic agent that stimulates platelet production and offers an alternative method for treatment of patients with ITP. In clinical trials, patients have achieved durable platelet count responses without clinically important side effects. Methods: We report the case of a 44 year-old female with refractory ITP who has achieved successful remission following treatment with romiplostim. Results: As previously described in Haematologica (2008;93:1445) this patient presented with purpura, menorrhagia, and a platelet count of 7,000. Throughout 2005 she had only transient responses to high dose dexamethasone, intravenous immunoglobulin, rituximab, and splenectomy. She was placed on romiplostim in August 2005 as part of a clinical trial and received a dose of 7 mcg/kg/week for approximately 50 weeks. She was able to tolerate dose reductions and by May 2007 her dose had been de-escalated to 3 mcg/kg/week, which she continued through 2009 as part of an open-label continuation study. In January 2010, after completion of the clinical trial, she began receiving romiplostim by prescription. She was able to gradually tolerate extended dosing intervals due to sustained platelet response. Her last dose was administered on October 27, 2010 and she has maintained a platelet count above 197,000 without further therapy. Conclusions: This case represents, to our knowledge, one of the longest maintained durable responses to romiplostim therapy. Romiplostim provides an alternative approach of treatment for ITP, and as evidenced by this case report, in some patients it may also lead to disease remission and eliminate the need for further treatment.

Download Full-text

Acute and Chronic Changes in Platelet Volume and Count After Cardiopulmonary Bypass Induced Thrombocytopenia in Man

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651061 ◽

1987 ◽

Vol 57 (01) ◽

pp. 55-58 ◽

Cited By ~ 37

Author(s):

J F Martin ◽

T D Daniel ◽

E A Trowbridge

Keyword(s):

Platelet Count ◽

Mean Platelet Volume ◽

Artery Bypass ◽

Bypass Graft ◽

Control Group ◽

Artery Bypass Graft ◽

Platelet Volume ◽

Young Males ◽

The Mean

SummaryPatients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 ± 0.11 × 1011/1 (n = 26) fell significantly to 1.35 ± 0.09 × 1011/1 immediately post-operatively (p <0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 ± 0.66 × 1011/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 ± 0.14 and 7.20 ± 0.14 fl respectively to a minimum of 6.16 ± 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 ± 0.33 × 1011/1, significantly higher than the pre-operative value (p <0.05), while their average mean platelet volume was 6.63 ± 0.21 fl, significantly lower than before surgery (p <0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.

Download Full-text

Successful long-term remission through tapering tocilizumab infusions: a single center prospective study

10.21203/rs.2.12756/v1 ◽

2019 ◽

Author(s):

Chayma Ladhari ◽

Pierre Le Blay ◽

Thierry Vincent ◽

Ahmed Larbi ◽

Emma Rubenstein ◽

...

Keyword(s):

Therapeutic Option ◽

Sustained Remission ◽

Single Center ◽

Open Label ◽

Open Label Study ◽

Treatment Interval ◽

Secondary Failure ◽

Term Maintenance

Abstract Background Strategic drug therapy for rheumatoid arthritis (RA) patients with prolonged remission is not well defined. According to recent guidelines, tapering biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) may be considered. We aimed to evaluate the long-term maintenance of tocilizumab (TCZ) treatment after the progressive tapering of infusions. Methods We conducted an exploratory, prospective, single-center, open label study, on RA patients with sustained remission for at least 3 months and treated with TCZ infusions every 4 weeks. The initial re-treatment interval was 6 weeks for the first 3 months. Thereafter, the spacing between infusions was determined by the clinician. Successful long-term maintenance following the tapering of TCZ infusions was defined by patients still treated after two years by TCZ with a minimum dosing interval of 5 weeks. Results Thirteen patients were enrolled in the study. Eight out of thirteen were still treated by TCZ after two years. Successful long-term maintenance was possible in six patients, with four patients maintaining a re-treatment interval of 8-weeks or more. We observed 5 patients with TCZ withdrawal: one for adverse drug reaction (neutropenia) and four with secondary failure. Patients achieving successful long-term maintenance with TCZ were significantly younger than those with secondary failure (p<0.05). In addition, RA patients with positive rheumatoid factor and anti-citrullinated peptide antibodies, experienced a significantly greater number of flares during our 2-year follow-up (p<0.01). Conclusions A progressive tapering of TCZ infusions seems possible in most of the patients. However, larger studies, including more patients, are needed to confirm this therapeutic option.

Download Full-text

Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽

10.1182/blood-2019-129274 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2352-2352

Author(s):

Tomas Jose Gonzalez-Lopez ◽

Fernando Fernandez-Fuertes ◽

Maria Cristina Pascual Izquierdo ◽

Isabel Caparros ◽

Silvia Bernat ◽

...

Keyword(s):

Platelet Count ◽

Median Time ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Previous Treatment ◽

Complete Response ◽

Platelet Response ◽

Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

Download Full-text

134 Long-Term Deutetrabenazine Treatment Is Associated with Sustained Treatment Response in Tardive Dyskinesia: Results from an Open-Label Extension Study

CNS Spectrums ◽

10.1017/s1092852920000504 ◽

2020 ◽

Vol 25 (2) ◽

pp. 284-285 ◽

Cited By ~ 1

Author(s):

Robert A. Hauser ◽

Hadas Barkay ◽

Hubert H. Fernandez ◽

Stewart A. Factor ◽

Joohi Jimenez-Shahed ◽

...

Keyword(s):

Adverse Events ◽

Percentage Change ◽

Extension Study ◽

Total Daily Dose ◽

Open Label ◽

Daily Dose ◽

Open Label Extension ◽

The Mean ◽

Over Time

Abstract:Background:In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.Methods:Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.Results:343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.Conclusions:Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

Download Full-text

A young woman with headache and seizures

Italian Journal of Medicine ◽

10.4081/itjm.2008.4.25 ◽

2013 ◽

pp. 25-29

Author(s):

A.M. Pizzini ◽

M. Silingardi ◽

I. Iori

Keyword(s):

Venous Thrombosis ◽

Cerebral Venous Thrombosis ◽

Mr Angiography ◽

Sinus Thrombosis ◽

Factor V Leiden ◽

Transverse Sinus ◽

Acute Onset ◽

Factor V ◽

Neuroimaging Techniques

CASE REPORT We describe a 31 year-old woman with headache and acute onset of seizures. Medical history and physical examination were unremarkable. She has been on therapy with oral contraceptives for many years for dysmenorrhea. A CT scan was negative, but MRI and MR-angiography showed left transverse sinus thrombosis. Screening for thrombophilia revealed hyperhomocysteinemia and Factor V Leiden heterozigousity. The patient received unfractionated heparin, followed by long-term anticoagulation with warfarin (INR 2-3). CONCLUSIONS Cerebral venous thrombosis is a rare cerebrovascular disorder, frequently in young adult (about 75% are women). The diagnosis might be difficult with consequent high long-term morbidity and mortality rate. New neuroimaging techniques (MRI and MR-angiography) and more effective treatment (anticoagulation and endovascular thrombolysis) have improved the prognosis and the natural history. The risk factors, the clinical presentation, the diagnostic evaluation and the management of cerebral venous thrombosis are reviewed.

Download Full-text

Long-Term Efficacy and Safety of Molidustat for Anemia in Chronic Kidney Disease: DIALOGUE Extension Studies

American Journal of Nephrology ◽

10.1159/000499111 ◽

2019 ◽

Vol 49 (4) ◽

pp. 271-280 ◽

Cited By ~ 10

Author(s):

Tadao Akizawa ◽

Iain C. Macdougall ◽

Jeffrey S. Berns ◽

Thomas Bernhardt ◽

Gerald Staedtler ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Hypoxia Inducible Factor ◽

Efficacy And Safety ◽

Open Label ◽

Multicenter Studies ◽

Parallel Group ◽

The Mean ◽

Term Management

Background: Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat. Methods: Both studies were parallel-group, open-label, multicenter studies of ≤36 months’ duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control. One study enrolled patients not receiving dialysis (n = 164), and the other enrolled patients receiving hemodialysis (n = 88). The primary efficacy variable for both studies was change in blood hemoglobin (Hb) level from baseline to each post-baseline visit, and safety outcomes included adverse events (AEs). Results: In patients not on dialysis, the mean ± SD Hb concentrations at baseline were 11.28 ± 0.55 g/dL for molidustat and 11.08 ± 0.51 g/dL for darbepoetin. The mean ± SD blood Hb concentrations throughout the study (defined as mean of each patient’s overall study Hb levels) were 11.10 ± 0.508 and 10.98 ± 0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. Similar proportions of patients reported at least one AE in the molidustat (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean ± SD Hb levels at baseline were 10.40 ± 0.70 and 10.52 ± 0.53 g/dL in the molidustat and epoetin groups, respectively. The mean ± SD blood Hb concentrations during the study were 10.37 ± 0.56 g/dL in the molidustat group and 10.52 ± 0.47 g/dL in the epoetin group. Proportions of patients who reported at least one AE were 91.2% in the molidustat group and 93.3% in the epoetin group. Conclusions: Molidustat was well tolerated for up to 36 months and appears to be an effective alternative to darbepoetin and epoetin in the long-term management of anemia associated with CKD.

Download Full-text

Efficacy of Extracorporeal Photopheresis (ECP) Monotherapy in the Treatment of Cutaneous T Cell Lymphoma.

Blood ◽

10.1182/blood.v110.11.2561.2561 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2561-2561

Author(s):

Larisa Geskin ◽

Francine Foss ◽

Madeleine Duvic ◽

David Straus ◽

Steven Horwitz ◽

...

Keyword(s):

Skin Disease ◽

Subsequent Treatment ◽

Topical Steroids ◽

Open Label ◽

Eligibility Criteria ◽

Skin Score ◽

The Mean ◽

Hands And Feet

Abstract Background: Mycosis Fungoides (MF) and its leukemic variant Sezary syndrome (SS) are disorders of malignant, skin homing helper/memory T-cells. MF presents with patches, plaques, or tumors, while SS presents with generalized erythroderma and blood involvement. Either can involve lymph nodes, blood, and viscera. A multi-center, open label, single arm clinical trial previously demonstrated the safety and efficacy of ECP as a monotherapy in the treatment of patients with advanced/refractory MF/SS (Edelson, et al, 1987, N Engl J Med, 316:297–303). The primary endpoint of this study was a ≥25% improvement in skin score maintained for at least 4 weeks. We present a long-term, secondary analysis of these patients to further evaluate clinical outcomes and predictors of response for ECP as a monotherapy in MF/SS. Partial (≥50%) and complete (≥90%) skin score responses, extent of skin disease, number of ECP treatments administered, and the time required to achieve 50% and 90% improvement in skin involvement were evaluated. Patients and Methods: Thirty-nine patients (pts) who met eligibility criteria were included in the secondary efficacy analysis as the intent-to-treat (ITT) patient population. Thirty-one pts with generalized erythroderma (GE) and 8 pts with extensive patch plaque (EPP) were treated with ECP on 2 consecutive days every 4–5 weeks for 3 months. No concomitant systemic medications for MF/SS were allowed on study; however, topical steroids could be applied to the hands and feet. Patients had received an average of 3.7 (range 0–13) prior therapies (systemic and topical). Immediately prior to undergoing ECP, all pts received oral doses of methoxsalen in order to achieve blood level concentrations ≥50 ng/mL. Skin improvement was calculated by comparing baseline skin score to skin scores on all subsequent treatment dates. The mean baseline skin score of the 39 ITT patients was 262 (median = 291) based on a maximum possible skin score of 400 points. Results: The median follow-up of the 39 ITT pts was approximately 4 years (range 9 days–7.8 years). Twenty-nine pts (74%) achieved at least a ≥50% improvement in skin score, and 16 pts (41%) achieved ≥90% improvement on ECP monotherapy. The type and extent of skin disease (GE vs. EPP) prior to the start of treatment did not predict response. Patients received a median of 12 (range 4–65) or 30.0 (range 12–109) individual ECP treatments to achieve a ≥50% or ≥90% response, respectively. The mean times to reach a ≥50% or ≥90% response were 8.4 ± 6 months (median=6.5) or 25.2 ±14.9 mos (median=19.6), respectively. The mean duration of a ≥50% response was 32.5 ± 28.6 mos, which included a median of 20 (range 0–153) ECP treatments. Median survival from date of diagnosis and from date of first ECP treatment was 10.6 yrs and 5.4 yrs, respectively. Conclusions: In this long-term, follow-up analysis, ECP monotherapy was associated with a significant and durable improvement in skin score in the majority of patients with MF/SS.

Download Full-text