Effective Treatment of Chronic Hand Dermatitis with 36 Continuous Months of Alitretinoin Administration: Report of Three Cases

2012 ◽  
Vol 16 (4) ◽  
pp. 267-271 ◽  
Author(s):  
Wayne P. Gulliver ◽  
Kenneth A. Baker
Keyword(s):  
Adverse Events ◽  
Treatment Period ◽  
Global Assessment ◽  
Current Medical ◽  
Continuous Treatment ◽  
Treatment Withdrawal ◽  
Prolonged Treatment ◽  
Safety And Efficacy ◽  
Hand Dermatitis

Background: Moderate to severe chronic hand dermatitis (CHD) is not well controlled by current medical strategies; however, recent studies have shown significant improvement in patients treated with up to 6 months of oral alitretinoin (9- cis-retinoic acid). The results of longer-term continuous treatment are lacking. Objective: To evaluate the long-term safety and efficacy of alitretinoin for the treatment of CHD. Methods: The Physician's Global Assessment (PGA) and Modified Total Lesion Symptom Score (MTLSS) were used to assess CHD improvement in three patients treated with alitretinoin (10–30 mg/d). Patients had routine bloodwork and were monitored for adverse events. Results: Significant improvement in MTLSS scores (≈ 76%) was seen at 2 months ( p < .002) and maintained for the 3-year treatment period with occasional dosage adjustments. No significant adverse events developed that necessitated treatment withdrawal. Conclusion: Alitretinoin was well tolerated in the treatment of these three CHD patients who were carefully monitored over this prolonged treatment period.

scholarly journals SUN-094 Long-Term Safety and Efficacy of Leuprorelin in Treating Central Precocious Puberty: A Large, Open-Label, Multicenter, Phase IV Study in China

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Xiaoping Luo ◽  
Ling Hou ◽  
Yan Zhong ◽  
Yu Yang ◽  
Pin Li ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Period ◽  
Precocious Puberty ◽  
Tanner Stage ◽  
Central Precocious Puberty ◽  
Chinese Patients ◽  
Gnrh Analogue ◽  
Open Label ◽  
Safety And Efficacy

Abstract BACKGROUND: Leuprorelin (Enantone®) is a gonadotropin-releasing hormone (GnRH) analogue used worldwide to treat central precocious puberty (CPP). This clinical trial aimed to evaluate the long-term safety and efficacy of leuprorelin in treating Chinese CPP children. Methods: This is the first, prospective, open-label, and multicenter study conducted from 2015 to 2018, in China. As a large interventional study, it included a four-week screening period, a 96-week treatment period, and a four-week safety follow-up period. Eligible subjects were treated with leuprorelin subcutaneously once every four weeks for 96 weeks. At the beginning of the study, subjects whose body weight ≥20 kg received a dose of 3.75 mg and those &lt;20 kg received a dose of 1.88 mg and then the dose was allowed to be adjusted during the study based on subject’s condition and investigator’s judgment. The primary endpoint was the incidence of adverse events during treatment, and the secondary endpoint was the percentage of subjects who had regression or no progression in Tanner stage at Week 96 compared with baseline. Results: A total of 307 CPP patients from 11 Chinese medical centers received leuprorelin, of which 305 (99.3%) were girls and 2 were boys (0.7%), with a mean (±SD) age of 7.95±0.982 years and a mean height of 133.68±7.108 cm. Two hundred eighty-three (92.2%) patients completed the 96-week treatment period. Two hundred fifty-two patients (82.1%) reported treatment-emergent adverse events (TEAEs)—most of which (79.5%) were mild to moderate. Only 33 (10.7%) patients experienced TEAEs that were considered related to leuprorelin. The most frequent (&gt;2%) drug-related TEAEs were injection site induration (4.6%, 14/307) and vaginal bleeding (2.3%, 7/305). After the 96-week treatment period, 83.5% female subjects had regression or no progression in Tanner stage compared with baseline (95% CI: 78.68%, 87.62%) and the 2 male subjects had progression of 1 point in Tanner stage genital score occurred at Week 12 and then remained stable throughout the study. By the end of the treatment period, the majority of subjects had decreased GnRH stimulated peak LH and FSH, as well as reduced sex hormone levels and bone age/chronological age ratio compared with baseline. The subjects also had increased predicted adult height and BMI after treatment. Conclusions: This Chinese study demonstrated that CPP was effectively treated in most patients who received leuprorelin (Enantone®) for nearly two years. Any drug-related adverse events were reported with low incidence (&lt;5%) and were consistent with the known safety profile of leuprorelin. Leuprorelin was shown to be well tolerated and effective in the management of CPP in Chinese patients.

scholarly journals Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world

2017 ◽  
Vol 10 (10) ◽  
pp. 343-359 ◽  
Author(s):  
Tjalf Ziemssen ◽  
Katja Thomas
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Mechanism Of Action ◽  
Real World ◽  
Continuous Treatment ◽  
The Real ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity. In high proportions of patients, preexisting disability remained stable or improved. Alemtuzumab is associated with a consistent safety profile over the long term, with no new safety signals emerging and the overall annual incidence of reported adverse events decreasing after the first year on treatment. Acyclovir prophylaxis reduces herpetic infections, and monitoring has been shown to mitigate the risk of autoimmune adverse events, allowing early detection and overall effective management. Data from clinical practice and ongoing observational studies are providing additional information on the real-world use of alemtuzumab. Recent evidence on the mechanism of action of alemtuzumab indicates that in addition to its previously known effects of inducing depletion and repopulation of T and B lymphocytes, it also results in a relative increase of cells with memory and regulatory phenotypes and a decrease in cells with a proinflammatory signature, and may further promote an immunoregulatory environment through an impact on other innate immune cells (e.g. dendritic cells) that play a role in MS. These effects may allow preservation of innate immunity and immunosurveillance. Together, these lines of evidence help explain the durable clinical efficacy of alemtuzumab, in the absence of continuous treatment, in patients with RRMS.

IRIS 6-Year Follow-Up: Sustained Survival and Declining Annual Rate of Transformation in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 25-25 ◽  
Author(s):  
Andreas Hochhaus ◽  
Brian J. Druker ◽  
Richard A. Larson ◽  
Stephen G. O’Brien ◽  
Insa Gathmann ◽  
...  
Keyword(s):  
Adverse Events ◽  
Blast Crisis ◽  
Randomized Study ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Continuous Treatment ◽  
Annual Rate ◽  
Interferon Α

Abstract Background: The International Randomized study of Interferon versus STI571 (IRIS) study demonstrated that imatinib has superior safety and efficacy relative to interferon-α plus cytarabine (IFN+ara-C). Patients on the imatinib arm achieved an estimated 5-year OS of 89%. To monitor the long-term responses achieved by patients on imatinib, the 6-year follow-up of the IRIS patient population is summarized. Methods: 1106 patients were randomly assigned to either imatinib or IFN+ara-C and evaluated for hematologic and cytogenetic responses, event-free survival, progression to accelerated-phase (AP) or blast crisis (BC), overall survival (OS), and frequency of adverse events and discontinuations. Results: The downward trend in the risk of disease progression on imatinib has continued with a 0.4% event rate (including loss of response) and a 0% rate of transformation to AP/BC attained between years 5 and 6. Of 553 who were randomized to imatinib, 364 (65.8%) remain on study drug at 6 years: 14 (2.5%) crossed over to the IFN arm, and 175 (31.6%) pts have discontinued from imatinib study therapy for any reason. The following reasons were cited for discontinuation from the IRIS study: adverse events, 23 patients (4.2%); unsatisfactory therapeutic effect, 66 patients (11.9%); protocol violation, 15 patients (2.7%); withdrawal of consent, 32 patients (5.8%); administrative problems, 6 patients (1.1%); and 16 patients (2.9%) elected to undergo a stem cell transplantation (SCT). Death was the reason for discontinuation for 10 (1.8%) patients, and 7 patients (1.3%) were lost to follow-up. The best observed complete hematologic response rate among patients receiving first-line imatinib was 97%. The best observed major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) rates were 89% and 83%, respectively, with 2 additional CCyR observed since the prior 5-year analysis. At the current 6-year follow-up, 325 patients are still in CCyR, another 24 had lost CCyR but regained it, 6 patients lost CCyR but remain in MCyR, and the remaining 9 patients never had a documented CCyR. Overall, an estimated 83% of patients were event-free, and 93% were free of progression to AP or BC at 6 years on imatinib study treatment, as patients were followed only for OS after discontinuation. After the second year on imatinib, the annual rate of events decreased every year, as did the annual relapse rate. Based on the current follow-up, a total of 66 (12%) patients have died (19 after SCT, 27 not due to CML). Estimated 6-year OS rate for all patients who received imatinib as initial therapy was 88%. When survival is censored at time of SCT for patients who proceeded to transplant, the estimated OS at 6 years is 91%. In an analysis of serious adverse events, no new safety issues were identified between the 5-year report and this analysis. Conclusions: The 6-year follow-up analysis of the IRIS population indicates that continuous treatment of chronic-phase CML with imatinib induces durable responses in a high percentage of patients with a decreasing rate of relapse and a favorable long-term safety profile.

Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy

2007 ◽  
Vol 67 (4) ◽  
pp. 547-554 ◽  
Author(s):  
M C Genovese ◽  
M Schiff ◽  
M Luggen ◽  
J-C Becker ◽  
R Aranda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Sleep Problems ◽  
Inadequate Response ◽  
C Reactive Protein ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Reactive Protein ◽  
Sf 36

Objective:To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis.Methods:Patients completing the 6-month, double-blind period were eligible to enter the long-term extension; patients received abatacept ∼10 mg/kg, plus disease-modifying antirheumatic drugs. Safety and efficacy (American College of Rheumatology (ACR) criteria responses, DAS28 (C-reactive protein), HAQ-DI, SF-36, Medical Outcomes Study Sleep Problems Index, fatigue VAS) were assessed through 2 years.Results:317 patients (218 from the abatacept and 99 from the placebo group) entered and 222 (70%) completed 18 months of long-term extension treatment. The incidence and type of adverse events were consistent between the double-blind and cumulative (double-blind plus long-term extension) periods. Rates of serious adverse events were 25.6 and 23.4 per 100 patient-years in the double-blind versus cumulative period. At 6 months and 2 years, using non-responder analyses, ACR responses in abatacept-treated patients were: ACR 20, 59.4% and 56.2%; ACR 50, 23.5% and 33.2%; ACR 70, 11.5% and 16.1%; HAQ-DI responses were 54.4% and 47.9%. At 6 months and 2 years, using post-hoc as-observed analyses, the percentage of patients (95% confidence interval) achieving DAS28 (C-reactive protein) low disease activity score (⩽3.2) and DAS28 (C-reactive protein)-defined remission (<2.6) increased from 18.3% (13.0, 23.5) to 32.0% (24.6, 39.4) and 11.1% (6.8, 15.3) to 20.3% (13.9, 26.6). Clinically meaningful improvements in SF-36, pain, fatigue and sleep problems were also maintained throughout the 2 years of abatacept treatment.Conclusion:No unique safety observations were reported during open-label exposure. Improvements in the signs and symptoms of rheumatoid arthritis, physical function and health-related quality of life observed after 6 months, were maintained throughout the 2 years in this population with difficult-to-treat disease.Trial registration number:NCT00124982.

New treatments for panic

1998 ◽  
Vol 13 (S2) ◽  
pp. 75s-81s ◽  
Author(s):  
JC Ballenger
Keyword(s):  
Panic Disorder ◽  
Adverse Events ◽  
Dropout Rate ◽  
Prolonged Treatment ◽  
Double Blind Study ◽  
Onset Of Action ◽  
Double Blind ◽  
New Treatments ◽  
To Receive

SummaryPanic disorder is a chronic condition for many patients and can be socially, emotionally and occupationally disabling. Until recently, clomipramine and alprazolam were the only drugs approved for its treatment. While widely used in the US and Europe, both belong to drug classes (tricyclics and benzodiazepines) with well-recognised side effects that can be problematic and thus limit their use. Recently, paroxetine became the first selective serotonin reuptake inhibitor to receive approval and licensing for panic disorder.The short- and long-term efficacy and tolerability of paroxetine in panic disorder has been established in clinical trials of almost 1,000 patients meeting Diagnostic and Statistical Manual (DSM)-IIIR criteria for panic disorder, with or without agoraphobia. In a 12-week double-blind study of 120 panic patients receiving standardised cognitive therapy, paroxetine was significantly more effective than placebo in reducing panic attack frequency. In a 12-week placebo-controlled comparison in 367 panic patients, paroxetine was at least as effective as clomipramine and better tolerated. There was also some evidence that paroxetine had an earlier onset of action than clomipramine.A 9-month extension of the placebo-controlled comparison with clomipramine showed that the efficacy of paroxetine and clomipramine is maintained when treatment is continued into the longer term. In a relapse prevention study, 105 responders to 3 months' treatment with paroxetine or placebo were re-randomised, either to continue existing treatment or to receive placebo for 3 months. Only 5% of patients who continued to take paroxetine experienced a relapse compared with 30% of those who switched to placebo (P = 0.002). Paroxetine was generally well tolerated. In the short-term trials, the frequency of withdrawals due to adverse events (7.3%) was lower than that for placebo (11.4%) or clomipramine (14.9%). In the longer term, the dropout rate due to adverse events increased in the clomipramine group (19.0%) but was unchanged in the paroxetine group (7.4%). Since most patients with panic disorder will require prolonged treatment, the long-term tolerability of paroxetine and its lack of potential for dependence are important advantages that will encourage good compliance with treatment and improve the quality of life of patients.

One-Year Open-Label Safety and Efficacy Study of Paliperidone Extended-Release Tablets in Patients With Schizophrenia

CNS Spectrums ◽  
2010 ◽  
Vol 15 (8) ◽  
pp. 506-514 ◽  
Author(s):  
Michelle Kramer ◽  
George Simpson ◽  
Valentinas Maciulis ◽  
Stuart Kushner ◽  
Yanning Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Extended Release ◽  
Tolerability Profile ◽  
Open Label ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Stabilization Phase ◽  
Open Label Extension ◽  
Paliperidone Extended Release

ABSTRACTIntroduction: This 52-week open-label extension (OLE) to a double-blind placebo-controlled recurrence prevention study examined the long-term safety and efficacy of flexibly-dosed paliperidone extended-release (ER) tablets in patients with schizophrenia.Methods: Patients entering the OLE either entered from the double-blind phase (placebo or paliperidone ER treatment) or entered directly from the run-in or stabilization phase (paliperidone ER) of the earlier study. During the OLE, patients were treated with flexibly-dosed paliperidone ER (3–15 mg/day; 9 mg starting dose). Safety and tolerability assessments included incidence of adverse events and extrapyramidal symptoms. Efficacy was also assessed.Results: The study population (n=235) was predominantly men (66%), 18–58 years of age. Twelve patients (5%) experienced an adverse event requiring treatment discontinuation. One or more serious treatment-emergent adverse events were reported in 13 patients (6%). There was one death. The mean Positive and Negative Syndrome Scale total score decreased from open-label baseline to endpoint for all groups, regardless of previous double-blind treatment (placebo or paliperidone ER).Conclusion: This year-long OLE provides information on the long-term safety and tolerability of paliperidone ER in patients with schizophrenia. The resulting safety and tolerability profile was similar to that seen in earlier short-term studies.

scholarly journals Safety and Efficacy of Switching Injected Peptide Long-Acting Somatostatin Receptor Ligands to Once Daily Oral Paltusotine: ACROBAT Edge Phase 2 Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A526-A527
Author(s):  
Monica R Gadelha ◽  
Murray B Gordon ◽  
Mirjana Doknic ◽  
Emese Mezősi ◽  
Miklós Tóth ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Period ◽  
Somatostatin Receptor ◽  
Study Drug ◽  
Receptor Ligands ◽  
Primary Analysis ◽  
Once Daily ◽  
Safety And Efficacy ◽  
Somatostatin Receptor Ligands ◽  
Long Acting

Abstract Patients with acromegaly not cured by surgery are often initially treated with injected peptide long-acting somatostatin receptor ligands (SRLs). Non-peptide small molecules can also activate the somatostatin receptor and do so with a high degree of precision for the target therapeutic receptor subtype. Paltusotine (formerly CRN00808) is a small molecule somatostatin type 2 (SST2) receptor agonist with high oral bioavailability (70%) and pharmacokinetic profile suitable for once daily dosing. In healthy volunteers, paltusotine has been shown to lower growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. We hypothesized that patients with acromegaly could switch from injected SRLs to once daily oral paltusotine while maintaining baseline IGF-1 levels. ACROBAT Edge (NCT03789656) was a single-arm study designed to evaluate the safety and efficacy of switching from injected SRLs to paltusotine in patients with acromegaly. The primary analysis population consisted of those who had not achieved normal IGF-1 levels despite stable therapy with long-acting octreotide or lanreotide. Eligible patients received their last injection of SRL 4 weeks prior to switching to once daily oral paltusotine monotherapy for a 13-week treatment period. The starting dose of 10 mg per day was uptitrated in 10 mg increments at specified study visits to a maximal dose of 40 mg per day based on protocol specified study drug toleration and IGF-1 criteria. The primary endpoint was change in IGF-1 from baseline to the completion of the 13-week treatment period. Statistical testing was based on non-parametric Wilcoxon Sign Rank test of whether the median change is different from zero. In addition, the rise in IGF-1 during a 4-week washout period was used to provide supportive evidence of efficacy. Twenty-five patients were enrolled in the primary analysis group, three patients discontinued from the study for non-study drug related reasons, two during the treatment period and one during the washout period after completing treatment. The primary endpoint was achieved as paltusotine treatment resulted in no significant change in IGF-1 levels at week 13 compared to baseline [change in IGF-1 =-0.034 (-0.107, 0.107), median (IQR), p&gt;0.6]. Of the 23 patients who completed the dosing period, 20 (87%) achieved IGF-1 levels at the end of treatment that were within 20% of baseline or lower. Median IGF-1 values rose significantly after paltusotine washout (p&lt;0.0001). The most common treatment-emergent adverse events (&gt;10%) included: headache, arthralgia, fatigue, peripheral swelling, paresthesia and hyperhidrosis. There were no discontinuations due to adverse events and no treatment related serious adverse events. These results suggest that patients with acromegaly treated with injected SRLs can switch to oral paltusotine while maintaining IGF-1 and that paltusotine appeared to be well tolerated.

Safety and Efficacy Of Long-Term Open-Label Romiplostim Dosing In Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3530-3530
Author(s):  
Michael D. Tarantino ◽  
James B. Bussel ◽  
Amy Geddis ◽  
Michael F. Guerrera ◽  
Alan K. Ikeda ◽  
...  
Keyword(s):  
Adverse Events ◽  
Board Of Directors ◽  
Research Funding ◽  
Pediatric Patients ◽  
Open Label ◽  
Advisory Committees ◽  
Safety And Efficacy ◽  
Platelet Counts ◽  
Equity Ownership

Abstract Background Chronic pediatric ITP is an autoimmune disorder characterized by increased platelet destruction and suboptimal platelet production, resulting in low platelet counts. Romiplostim is a peptibody that stimulates platelet production via activation of the thrombopoietin (TPO) receptor. Romiplostim increased and maintained platelet counts in thrombocytopenic children with ITP in a phase 1/2 trial. Patients who completed this study or an ongoing phase 3 trial were given the option of rolling over into an open-label long-term extension study. Objectives To evaluate the safety and efficacy of long-term use of romiplostim in pediatric ITP. Methods Patients received weekly subcutaneous injections of romiplostim; the starting dose was the last dose in the prior study. Patients who had received placebo started at 1 μg/kg. Dose adjustments targeted platelet counts in the range of 50–200 x 109/L. The maximum allowed romiplostim dose was 10 µg/kg. Assessments of adverse events, concomitant medications, and local platelet counts were performed weekly. The primary endpoint was incidence of adverse events. The protocol did not require bone marrow biopsies to be performed, but when performed, specimens were submitted to a central lab for analysis. Patients who were on a stable dose had the option to receive romiplostim at home; patients and their caregivers then recorded dosing date, time, volume administered, and any dosing errors. Patients who turned 18 years of age during this study were permitted to remain on study. Results Twenty-two patients (N = 12 from the phase 1/2 study and N = 10 from the phase 3 study) were treated with romiplostim for up to 172 weeks (3.3 years). Baseline demographics included a median age of 12.0 years (range 3–16), 50% male, and 18.2% with prior splenectomy. Median romiplostim treatment duration was 89.0 weeks (range 3–172); median total number of doses was 64 (range 3–171); median average weekly romiplostim dose was 4.0 µg/kg (range 1–10), including ramp up to stable dose; and median maximum dose was 8.0 µg/kg (range 1–10). Of the 4 patients who discontinued the study, 3 withdrew consent and 1 was noncompliant; no patients withdrew due to safety issues and 18 continued on study. After the first week of this extension study, which for some patients was the first week of romiplostim, median platelet counts remained above 50 x 109/L throughout the study, and were in the target range of 50–200 x 109/L for all visits but weeks 76 and 156 (Figure). The median romiplostim dose (Q1, Q3) was 6.0 (2.0, 8.0) µg/kg at week 1 and 3.5 (0.0, 7.0) µg/kg at week 168 (Figure). Four patients discontinued romiplostim. Eight patients received rescue medications (defined as medications used for platelet counts < 10 x 109/L, bleeding/wet purpura, or investigator decision) which included immunoglobulins (3 patients), tranexamic acid (3 patients), platelet transfusion (1 patient), aminocaproic acid (1 patient), and prednisone (1 patient). Four patients had serious adverse events (asthma, hemangioma, hypotension, infection, thrombocytopenia, and transfusion reaction) and 1 had life-threatening adverse events (infection and thrombocytopenia). None of the serious adverse events were deemed treatment-related by the investigators. There were no fatal adverse events. Twelve patients had bleeding adverse events; 2 of which were deemed treatment-related (gingival bleeding and petechiae). Bleeding adverse events included epistaxis (4 patients); petechiae (3 patients); gingival bleeding (2 patients); hemorrhage (2 patients); and bleeding from the anus, injection site, lip, and mouth (1 patient each). No bone marrow biopsies were performed as part of this study. Conclusion In this open-label extension study, long term treatment with romiplostim maintained platelet counts in pediatric patients with chronic ITP without significant toxicity. Future results from this ongoing study will provide additional safety and efficacy data regarding long-term use of romiplostim in children with ITP. Disclosures: Tarantino: Pfizer: Membership on an entity’s Board of Directors or advisory committees; Octapharma: Membership on an entity’s Board of Directors or advisory committees; Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; BPL: Membership on an entity’s Board of Directors or advisory committees; Baxter: Membership on an entity’s Board of Directors or advisory committees; Amgen: Membership on an entity’s Board of Directors or advisory committees. Off Label Use: Romiplostim is approved for the treatment of adults with chronic ITP. Romiplostim is not approved for the treatment of pediatric patients with chronic ITP. Bussel:Amgen: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Symphogen: Membership on an entity’s Board of Directors or advisory committees. Nie:Amgen: Employment, Equity Ownership. Eisen:Amgen: Employment, Equity Ownership.

scholarly journals Mesenchymal stem cell-derived neural progenitors in progressive MS

2020 ◽  
Vol 8 (1) ◽  
pp. e928
Author(s):  
Violaine K. Harris ◽  
James W. Stark ◽  
Sophia Yang ◽  
Shayna Zanker ◽  
John Tuddenham ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Adverse Events ◽  
Neural Progenitors ◽  
Sustained Improvement ◽  
Safety And Efficacy ◽  
Biomarker Analysis ◽  
Chemokine Ligand ◽  
Class Iv

ObjectiveTo determine the long-term safety and efficacy of repeated intrathecal (IT) administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NPs) in patients with progressive MS by evaluating subjects 2 years after treatment.MethodsTwenty subjects were enrolled as part of a phase I, open-label single-arm study of 3 IT injections of MSC-NPs spaced 3 months apart. Subjects were evaluated for adverse events and disability outcomes including the Expanded Disability Status Scale (EDSS) and the timed 25-foot walk (T25FW). Long-term evaluation was conducted 2 years after the third treatment. CSF was collected before and 3 months after treatment.ResultsEighteen of the 20 study participants completed the full 2-year follow-up protocol. There were no long-term adverse events associated with repeated IT-MSC-NP treatment. Seven subjects showed sustained improvement in EDSS after 2 years, although the degree of improvement was not maintained in 5 of the subjects. Three of the 10 ambulatory subjects showed sustained improvement in the T25FW after 2 years. CSF biomarker analysis revealed a decrease in C-C motif chemokine ligand 2 (CCL2) and an increase in interleukin 8, hepatocyte growth factor, and C-X-C motif chemokine ligand 12 (CXCL12) after treatment.ConclusionsSafety and efficacy of repeated IT-MSC-NP treatment was sustained for 2 years; however, the degree of disability reversal was not sustained in a subset of patients. CSF biomarkers altered in response to IT-MSC-NP treatment may reflect specific immunoregulatory and trophic mechanisms of therapeutic response in MS.Classification of evidenceThis study provides Class IV evidence that for patients with progressive MS, IT administration of MSC-NPs is safe and effective. The study is rated Class IV because of the absence of a non–IT-MSC-NP-treated control group.Clinicaltrials.gov identifierNCT01933802.

Update on the Pharmacotherapy of Obesity

1998 ◽  
Vol 32 (1) ◽  
pp. 88-102 ◽  
Author(s):  
Jennifer Cerulli ◽  
Ben M Lomaestro ◽  
Margaret Malone
Keyword(s):  
Food Intake ◽  
Adverse Events ◽  
English Literature ◽  
Maladie Chronique ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Medline Search ◽  
Regulate Food Intake

OBJECTIVE To review recent developments in the pharmacotherapy of obesity, including the agents currently approved for use in the management of obesity and those under development. DATA SOURCES A MEDLINE search from January 1990 to July 1997 was conducted to identify English literature available on the pharmacotherapy of obesity. The search was supplemented by a review of the bibliographies of identified literature. STUDY SELECTION All controlled and uncontrolled trials were reviewed. When available, double-blind, placebo-controlled trials were used preferentially. DATA EXTRACTION Agents were reviewed with regard to mechanism of action, clinical trial data regarding efficacy, adverse effects, pharmacokinetics, drug interactions, and contraindications where information was available. Study design, selected population, results, and adverse effect information were included. DATA SYNTHESIS: The anorexiants currently available or under development for the management of obesity regulate food intake and satiety via the adrenergic and/or serotonergic pathways. Clinical trials have shown a 10–15% weight loss can typically be anticipated; however, little long-term safety and efficacy data are available. Adverse events tend to be mild and self-limiting, but serious adverse events can occur. Treatment options under development include thermogenic agents, digestive inhibitors, and analogs and antagonists of hormones that regulate food intake and satiety. CONCLUSIONS Several mechanisms to control weight are currently under investigation for the management of obesity. Since obesity is a chronic condition, further studies should be conducted to evaluate the long-term safety and efficacy of these agents and the role of combination therapy using different modalities. OBJETIVO Revisar los recientes avances farmacológicos en el tratamiento de la obesidad, incluyendo aquellos medicamentos actualmente aprobados para este uso y otros que todavía se encuentran en desarrollo. FUENTES DE INFORMACION Se realizó una búsqueda computarizada de MEDLINE para determinar artículos publicados en la literatura inglesa entre enero de 1990 a julio de 1997. Además, se utilizarón las referencias citadas en los artículos identificados en la búsqueda. SELECCION DE ESTUDIOS Estudios clínicos de tipo controlados y no-controlados fueron incluidos en el análisis. Se le dió preferencia a aquellos estudios clínicos que eran de diseño doble ciego, controlados, y que usaron un grupo control de placebo. EXTRACCIÓN DE DATOS Los medicamentos fueron evaluados de acuerdo al mecanismo de acción farmacológica, la información ciéntifica relacionada con su eficacia, efectos secundarios, farmacocinética, interacciones de medicamentos, y contraindicaciones de uso. El disefio ciéntifico utilizado en los estudios clínicos, el grupo de pacientes incluido en los estudios, los resultados obtenidos, y los efectos adversos fueron además incluidos en el análisis. SINTESIS Los medicamentos anoréxicos actualmente disponibles para el tratamiento de la obesidad regulan la cantidad de alimentos ingeridos y la sensación de saciedad através de los mecanismos adrenérgicos y de serotonina. Los estudios clínicos disponibles han demostrado que usualmente se puede esperar de un 10–15% de perdida de peso con el uso de estos medicamentos. Sin embargo, no existe mucha información relacionada al uso seguro y la eficacia de estos medicamentos a largo plazo. Los efectos adversos observados con estos medicamentos tienden a ser leves y de corta duración, pero efectos adversos severos pueden ocurrir. Otras opciones de tratamiento incluyen medicamentos termogénicos, inhibidores digestivos, y análogos y antagonistas de diferentes hormonas que regulan la ingestión de alimentos y la sensación de saciedad. CONCLUSIONES Actualmente, algunos de los mecanismos relacionados con el control de peso están siendo investigados para poder determinar futuros tratamientos de la obesidad. Debido a que la obesidad es un problema crónico, se tienen que realizar estudios clínicos adicionales disefiados para evaluar la eficacia y el uso seguro de estos medicamentos a largo plazo. Además, el uso de estos medicamentos en combinación tiene que ser evaluado. OBJECTIF Réviser les développements dans la pharmacothérapie de l'obésité ainsi que les médicaments actuellement utilisés et ceux qui sont en développement. REVUE DE LITTÉRATURE Une recherche sur MEDLINE a été entreprise pour identifier les publications en langue anglaise concernant le traitement de l'obésité et publiées entre janvier 1990 à juillet 1997. Les bibliographies des références pertinentes ont aussi été scrutées. SÉLECTION DES ÉTUDES Toutes les études, contrôlées ou non, ont été révisées. Cependant, les études à double insu ou contrôlées par placebo ont été préférées. EXTRACTION DE L'INFORMATION: Chaque médicament a été révisé pour le mécanisme d'action, les données d'efficacité clinique, les réactions indésirables, la pharmacocinétique, les interactions médicamenteuses, et les contre-indications. Le devis des études, la population à l'étude, les résultats, et les réactions indésirables sont présentes. RÉSUMÉ Les anorexigènes disponibles sur le marché contrôlent l'apport alimentaire et la satiété par une action sur les voies adrénergiques et sérotoninergiques. Les études cliniques ont démontré qu'une perte de poids de 10–15% est un objectif réaliste. Cependant, peu d'études d'efficacité et de sécurité à long terme sont disponibles. Les réactions indésirables sont généralement mineures et se résolvent spontanément. Cependant, des réactions sévères peuvent aussi survenir. De nouvelles avenues thérapeutiques sont en développement. Elles comportent des agents thermogéniques, des inhibiteurs de la digestion, des analogues et antagonistes hormonaux qui régissent l'apport alimentaire et la satiété. CONCLUSIONS Plusieurs stratégies de contrôle de l'obésité sont actuellement en investigation. Puisque l'obésité est une maladie chronique, des études devraient être réalisées pour évaluer l'efficacité et la sécurité des médicaments ainsi que le rôle des thérapies combinées.

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