Efficacy Of Long-term Therapy Research Articles

RESULTS OF LONG-TERM THERAPY WITH A BIOSIMILAR OF ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.

The study aimed to assess the safety, immunogenicity, and efficacy of long-term therapy with biosimilar of eculizumab (Elizaria®) in PNH patients. The study included 30 patients with PNH who had completed previous clinical trials. Of these, 25 patients continued receiving the biosimilar product, and 5 patients switched from the originator product Soliris. The maximum duration of follow-up was 104 weeks, during which the investigational product was administered 52 times at a standard dose. Throughout the study, the levels of LDH, hemoglobin, reticulocytes, and PNH clone remained stable compared to baseline, regardless of the previous therapy (p > 0.05). There were no significant differences in the number of patients with chronic kidney disease at different visits, as well as in the number of patients who received donor red blood cell and platelet transfusions during the study (p > 0.05). There were two cases of adverse reactions reported in two patients (6.6%): elevated aspartate aminotransferase (3.3%) and alopecia (3.3%). Immunogenicity analysis showed no significant differences in the frequency of anti-drug antibody detection compared to baseline (p > 0.05). The study findings confirm the long-term efficacy and safety of biosimilar in patients with PNH.

ID: 214525 Utilizing intraoperative EMG and Post-Operative Paresthesia Thresholds to Quantify Post-Synaptic Excitability Following Burst SCS

Burst spinal cord stimulation (SCS) has demonstrated superior relief from overall pain and a reduction in back and leg pain compared to traditional tonic neurostimulation therapies. However, nearly 80% of patients have 2 or more non-contiguous pain areas. This can affect the ability to effectively program stimulation and the long-term efficacy of therapy. Multiple BurstDR region programming is a new option to treat multi-site pain by interleaving stimulation at multiple areas along the spinal cord. Prior intraoperative studies have shown that BurstDR stimulation provides broader myotomal coverage at a lower recruitment threshold. The overall goal of this study is to use changes in intraoperative EMG threshold and post-operative paresthesia thresholds to optimize burst stimulation programming.

ID:16446 Utilizing Intraoperative Neuromonitoring to Program Multiple Areas of BurstDR SCS for Treatment of Chronic Pain

Burst spinal cord stimulation (SCS) has demonstrated superior relief from overall pain and a reduction in back and leg pain compared to traditional tonic neurostimulation therapies. However, nearly 80% of patients have 2 or more non-contiguous pain areas. This can affect the ability to effectively program stimulation and the long-term efficacy of therapy. Multiple BurstDR region programming is a new option to treat multi-site pain by interleaving stimulation at multiple areas along the spinal cord. This study aims to develop a method for programming SCS using EEG and EMG based biomarkers recorded via standard intraoperative neuromonitoring protocols.

A proposed definition of remission from chronic pain, based on retrospective evaluation of 24-month outcomes with spinal cord stimulation

ABSTRACTObjective: In the treatment of chronic diseases, remission is commonly used as a meaningful treatment goal, synonymous with the absence of significant clinical signs and symptoms of a disease, but not representing a cure. The objective of this paper is to propose a definition for remission for use as an outcome to evaluate the long-term efficacy of therapies for chronic pain.Methods: Data from a randomized clinical trial (NCT01609972) testing the efficacy of spinal cord stimulation in low back and leg pain subjects was used to evaluate the association between pain and functional outcomes and identify the cut-off value to predict remission. Available data over 24-month assessment period included visual analog score (VAS), disability (Oswestry Disability Index [ODI]), patient and clinician global impression of change (PGIC and CGIC), and patient satisfaction. Cluster analysis, Pearson’s correlation coefficients, sensitivity, and specificity analyses were used to evaluate its utility in predicting higher patient functionality and satisfaction.Results: Though the term remission has been used in the chronic pain field, a consistent definition has not been previously established. Based on the analysis of the clinical data, we propose that a sustained (≥6 months) pain score of ≤3.0 cm out of 10 cm on VAS be defined as remission. Applying this definition to the clinical trial data: subjects in remission at 24 months versus non-remitters were significantly more likely to be in the highest functional category of minimally disabled according to the ODI (31.5 vs. 8.2%, respectively, p = 0.001), and be ‘very satisfied’ (75.7 vs 22.6%, respectively, p < 0.001).Conclusions: The validity of the proposed definition of remission is supported by the persistence of remission in this study group, and its correspondence with patient satisfaction, and reduced disability. Further evaluation of the definition using clinical data from other long-term studies is needed.Trial registration: ClinicalTrials.gov identifier: NCT01609972.

Efficacy and safety of long-term therapy for high-grade glioma with temozolomide: A meta-analysis.

Further treatments are warranted in preventing recurrence or progression for high-grade glioma (HGG) patients having achieved stable disease with tolerable toxicity after the Stupp regimen (6 cycles of temozolomide). This meta-analysis aims to extensively evaluate the safety, feasibility, and efficacy of long-term therapy with temozolomide (>6 cycles) for these patients. We systematically searched the pubmed, Embase and Chinese Biomedical (CBM) databases using the strategy of combination of free-text words and MeSH terms. The efficacy indicators are hazard ratio (HR) for the pooled analysis of overall survival (OS) and progression free survival (PFS). The safety indicator is risk ratio (RR) for the pooled analysis of adverse effects. Six studies comprising a total number of 396 patients met all inclusion and exclusion criteria were included. No heterogeneity and publication bias were observed across each study. It was found that patients could obtain benefits from long-term administration of temozolomide both in OS (HR 2.39, 95% CI 1.82–3.14) and PFS (HR 2.12, 95% CI 1.56–2.89). In addition, the results showed that the patients receiving long-term administration of temozolomide did not experience additional toxicity over that of the Stupp regimen (6 cycles of temozolomide). It could be concluded that it's efficacious and safe for HGG patients to receive long-term therapy with temozolomide. Nevertheless, more randomized controlled trials (RCTs) should be carried out to verify this conclusion.

Real-life Efficacy of Omalizumab After 9 Years of Follow-up.

Omalizumab is frequently used as add-on treatment to inhaled corticosteroids (ICS) and long-acting β2-agonists in patients with suboptimal control of severe asthma. Patients with severe asthma will typically require chronic treatment, although due to the limited amount of data available there are still some concerns about the safety and efficacy of long-term therapy with omalizumab. Herein, in an extension of a previous 4-year study, we report disease-related outcomes of 8 patients with severe persistent allergic asthma who have been followed for a total of 9 years in a real-life setting. Both quality of life (QoL) (evaluated using the Juniper Asthma-Related QoL Questionnaire [AQLQ]) and forced expiratory volume in 1 second (FEV1) showed sustained improvement at 9 years. The median values of AQLQ and FEV1 at 4 years were 5.5 and 82.0% compared to 5.9 and 85.5%, respectively, at 9 years, which were all significantly increased from baseline. After 9 years, the mean annual number of severe exacerbations was 0.63 compared to 5 at baseline. There also appeared to be a trend toward use of a lower dose of ICS at longer follow-up times. After 9 years, there were no safety concerns for continued use of omalizumab, and no asthma-related hospitalizations or emergency department visits were documented over the last 5 years. The present analysis is the longest reported clinical follow-up of omalizumab. Long-term maintenance treatment with omalizumab for up to 9 years is associated with continued benefits in reducing symptoms, exacerbations, and medication burden without any safety concerns.

Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule

Background/Aims: Adult T-cell leukemia/lymphoma (ATL) is a very aggressive T cell malignancy that carries a poor prognosis, primarily due to its resistance to chemotherapy and to life-threatening infectious complications. Interferon-alpha (IFNα) has been used in combination with the anti-retroviral drug zidovudine to treat patients with ATL. However, the efficacy of long-term therapy is significantly limited due to the systemic toxicity of IFNα. Methods: We utilized phage display library screening to identify short peptides that specifically bind to Jurkat T lymphocyte leukemia cells. By fusing the Jurkat-binding peptide to the C-terminus of IFNα, we constructed an engineered chimeric IFNα molecule (IFNP) for the treatment of ATL. Results: We found that IFNP exhibited significantly higher activity than wild type IFNα in inhibiting the growth of leukemia cells and inducing cell blockage at the G0/G1 phase. The synthetic IFNP molecule exerted its antitumor activity by upregulating the downstream genes involved in the STAT1 pathway and in apoptosis. Using a cell receptor binding assay, we showed that this Jurkat-binding peptide facilitated the binding affinity of IFNα to the cell surface type I IFN receptor. Conclusion: The isolated Jurkat-binding peptide significantly potentiates the therapeutic activity of IFNα in T lymphocyte leukemia cells. The engineered IFNP molecule may prove to a novel antitumor approach in the treatment of patients with ATL.

Editorial: Long Term Follow-Up of Visual Acuity After anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration

Long term follow-up of visual acuity in macular degeneration represents an important issue in the management of elderly population. Previous study on macular photocoagulation could demonstrate after five years of follow-up untreated eyes had a mean visual loss of 7.1 lines, while laser treated eyes had lost 5.2 lines [1]. Most clinical studies on anti-VEGF therapies have a follow-up of 24 months such as ANCHOR study or MARINA study [1], [2]. More recently Long term efficacy of therapy was evaluated in SEVENUP study considering outcome evolution of ANCHOR, MARINA and HORIZON study [3], [4]. Bevacizumab and ranibizumab in a monthly protocol had also the same visual outcome in the CATT study in a monthly regimen [5]. This could also be confirmed at one year in a treat and extend protocol [6].

Management of ventricular arrhythmias in suspected channelopathies.

Although structural heart disease remains the predominant substrate for ventricular arrhythmia, channelopathies including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndrome (ERS) are less common but important contributing entities. These etiologies require specific therapies potentially contrary to empirical management of arrhythmias associated with structural heart disease. Conventional therapy including antiarrhythmic drug therapy may not only fail to resolve unstable arrhythmias but worsen them. Additionally, channelopathy patients with implantable cardioverter defibrillators (ICD) and arrhythmic storms represent a major challenge, and the acute care team needs to be cognizant of unique circumstances that require specific acute therapies beyond empirical advanced life support algorithm recommendations.1 Successful and considered acute management of ventricular arrhythmias is contingent on a number of variables, including knowledge of the cardiac substrate or potential substrate; form, mechanism, and precipitants of ventricular arrhythmias; and acute effect of potential therapies. In the longer term, an understanding of the natural history of the channelopathy along with the efficacy of long-term therapy will lead to superior outcomes. This review will present the risk of ventricular arrhythmias associated with these uncommon entities, the evolving understanding of the mechanism of arrhythmia, and the mechanistic basis of therapies along with a clinical approach to summarize the evidence pertaining to acute and long-term management. Patients with a prolonged QT interval are at risk of sudden cardiac death (SCD) due to Torsade de Pointes (TdP; Figure 1). Most patients with congenital LQTS are asymptomatic and diagnosed incidentally on electrocardiogram screening or following family screening. However, syncope, aborted SCD, or SCD may be the first presentation. Most arrhythmic events in congenital LQT1 occur during physical or emotional stress, at rest or in association with sudden auditory stimulation in LQT2, and during sleep or rest in LQT3 …

Deferasirox: appraisal of safety and efficacy in long-term therapy.

Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.

An open‐label pilot study of alefacept for the treatment of pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a chronic inflammatory disease that causes painful cutaneous ulcers that are difficult to treat. Currently, systemic immunosuppressants, often including prednisone, are the mainstay of therapy. Long-term therapy with these agents is often required which exposes patients to possible adverse effects. An alternative treatment that is safe and effective is truly needed. To study the efficacy and safety of alefacept, which inhibits T-cell activation and selectively reduces the T-cell population, for treatment of PG. In this prospective open-label pilot study, four patients diagnosed with PG received weekly doses of 15 mg alefacept intramuscularly for 20 weeks with 12-week treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving remission as defined by a Physician Global Assessment (PGA) of 'clear' or 'almost clear.' Secondary endpoints included proportion of patients achieving 50% improvement in PG lesion size (measured in mm) and proportion of patients achieving resolution of inflammation (an erythema score of 0 and a border thickness of 0 on scales of 0-4). By week 20, one (25%) of the four patients achieved remission, two showed marked improvement in severity on PGA, and one had slight improvement. One patient showed a 98% decrease in lesion size; two other patients evidenced a decrease in the number of small lesions as well as improvements in primary lesion sizes, but did not surpass the 50% criterion. All four patients showed improved erythema scores during treatment, though only one patient showed a complete resolution of inflammation. It may be difficult to generalize the results of this study to a larger population of patients with PG due to the small sample size and lack of a control group. A longer treatment interval might have been required. Safety and efficacy of long-term therapy is unknown. In this pilot study it appears that alefacept treatment may significantly reduce PG severity levels as evidenced by improvement in PGA, Subject Global Assessment, and inflammation scores in all patients. Alefacept may be a safe and effective alternative to current systemic immunosuppressants used to treat PG. Double-blinded, controlled trials are necessary to further evaluate the safety and effectiveness of this treatment.

Multimodality Treatment of Chronic Pancreatitis: Can We Prevents Hospital Admission?

Background & Aims: Efficacy of endoscopic therapy for chronic pancreatitis (CP) has typically been evaluated by improvement in pain score. Unfortunately accurate evaluation of pain is difficult since most patients are already on pain medication when undergoing endoscopic therapy. Our aim is to determine the efficacy of multimodality treatment of chronic pancreatitis on the rate of hospitalization. Methods: 247 patients (174 male, mean age 51 ± 13 y/o) with CP associated with pain were endoscopically treated between December 2001 and November 2006 and followed prospectively. Therapy offered included ERCP with pancreatic duct stenting (PD stent), extracorporeal shock wave lithotripsy (ESWL), and celiac plexus block (CPB). Long term efficacy of therapy was based on the absence of recurrent admissions for abdominal pain or pancreatitis after therapy, excluding post-procedural admission. Multivariate analysis were effected on the following factors to assess prediction of successful treatment (Age (<55 versus ≥55 y/o), gender, etiology (alcoholic or not), PD stent (yes versus no), ESWL, CPB). Results: Therapy included a mean of 3.6 ± 2.9 ERCPs in 240 (97%) patients with 166 (67%) patients receiving a PD stent, 37 (15%) patients underwent a mean of 1.2 ± 0.7 ESWL (range 1-4) and 42 (17%) patients received a mean of 2.2 ± 2 CPB (range: 1-8). A total of 154 (62%) patients did not require further admission post therapy over a median period of three years (range:1-5). Multivariate logistic regression analysis identified only PD stent as a predictor of long term success (see table). Conclusions: Endoscopic treatment of chronic pancreatitis is efficacious in 62% of patients undergoing multimodality therapy. PD stent placement appears to be a predictor of success in preventing long -term hospitalization post therapy. Tabled 1Predictive factor of successful treatment Factors P value Odds ratio 95% CI Gender 0.970 1.01 0.53-1.93 Age 0.051 1.77 1.00-3.13 Etiology 0.292 0.72 0.38-1.33 PD stent 0.007 0.43 0.24-0.79 ESWL 0.807 0.91 0.44-1.90 CPB 0.293 0.68 0.33-1.40 Open table in a new tab

Significant Changes of Peripheral Perfusion and Plasma Adrenomedullin Levels in N-Acetylcysteine Long Term Treatment of Patients with Sclerodermic Raynaud's Phenomenon

The unclear pathogenesis of scleroderma vascular lesions makes treatment of Raynaud's phenomenon (RP) in Systemic Sclerosis (SSc) patients very difficult and a new effective treatment is requested. Recently, a powerful antioxidant agent, the N-acetylcysteine (NAC) has been shown to decrease the frequency and severity of RP in SSc patients. Subsequently, using functional infrared imaging, we showed that a single 1-hour NAC infusion in these patients caused a significant increase of skin temperature. The aim of this study was to demonstrate the efficacy of long term therapy with NAC in an open clinical trial evaluating clinical, instrumental and laboratory parameters. Patients started the treatment receiving for two years, from October to May, intravenous NAC infusions of 15 mg/kg per hour each, for 5 consecutive hours, every two weeks. Before and after each infusion, patients underwent both Laser Doppler perfusion Imaging (LDPI) for the evaluation of the digital perfusion and a blood test to ascertain the plasma adrenomedullin (AM) levels. The NAC infusion increased global hands perfusion and induced a significant decreasing of plasma AM concentrations. Side effects were negligible, easy to control and reversible. Reduction of frequency and severity of RP attacks was recorded. In conclusion, NAC seems to act as an effective vasodilatator in the treatment of RP secondary to SSc and, in addition, it induced significant changes in plasma levels of AM, a potent vasodilator endothelial-derived peptide.

Efficacy and tolerability of long-term therapy using high lamivudine doses for the treatment of chronic hepatitis B.

A long-term follow-up study was carried out to evaluate the tolerability and efficacy of long-term therapy (1 to 3 years) with high doses (150 or 300 mg daily) of lamivudine for chronic hepatitis B. Thirty-two patients were studied, including those who were seronegative for hepatitis B e antigen (HBeAg), as well as those with decompensated liver cirrhosis. Viral DNA clearance was monitored by using end-point dilution polymerase chain reaction (PCR), a highly sensitive method. Hepatitis B virus (HBV) polymerase gene mutations associated with resistance were determined by sequencing. Response to lamivudine in the sixth month was observed in 19/32 (59.4%) patients. With one exception, viral DNA results observed at this time were maintained. The YMDD mutation was detected in 12 nonresponder patients (9 YVDD, 2 YIDD, and 1 mixed population Y(V/I)DD), generally associated with the L528M mutation. Re-takeover by the wild type was observed 6 to 18 months after lamivudine withdrawal. Lamivudine response rates in noncirrhotic and cirrhotic patients were 9/18 (50%) and 10/14 (71.4%), respectively. HBeAg to anti-HBe seroconversion was found after different periods in all responder patients. Hepatitis B surface antigen (HBsAg) clearance and anti-HBs seroconversion were occasionally found. In nonresponder patients, resistant mutants appeared up to the second year of lamivudine therapy. In spite of the presence of resistant mutants, maintenance of therapy was usually associated with a lower viral load. In responder patients, maintenance of therapy was associated with continued absence of detectable HBV DNA in serum, as monitored by highly sensitive methods. No significant side effects caused by lamivudine were observed in our patients, even in those with liver cirrhosis.

Role of transesophageal pacing in recurrent atrial fibrillation. Experience with propafenone.

To assess the role of transesophageal pacing (TP) at very high rates in the follow-up of patients with recurrent and sustained paroxysmal atrial fibrillation (AF) on therapy, the authors studied 15 patients (10 women, 5 men; aged forty-four to seventy-seven years old). Of them only 1 had a mild mitral regurgitation; none had hyperthyroidism or acute ischemic heart disease. They tested propafenone (P) at a dose of 1.4-2 mg/kg over ten minutes as an intravenous bolus and 0.5 mg/minute as intravenous maintenance for two hours and then 300 mg twice daily orally and chronically. Serial TPs at very rapid rates (up to 600 bpm) were performed to test the long-term efficacy of P to prevent paroxysmal AF. The mean follow-up was fifteen months (nine to twenty-four months). Intravenous P converted AF in five to ninety minutes (mean twenty-one minutes) in 9/15 patients (conversion rate of 60%); in an additional 4 patients oral P converted AF in two to fifteen hours. In the other 2 patients P failed to convert AF. Three patients experienced recurrence of AF in the early follow-up. Of the 10 patients who completed the entire protocol, only 1, who had mild mitral prolapse regurgitation and AF induction by TP, experienced new episodes of AF during follow-up. No significant side effects were noted during P therapy. Propafenone appears safe and effective for controlling and preventing recurrent and sustained AF. Transesophageal pacing is a valid tool for predicting the efficacy of long-term therapy in the follow-up of patients with paroxysmal atrial fibrillation.

ACYCLOVIR SUPPRESSES RECURRENT LABIAL HERPES.

Several studies have documented the efficacy of long-term therapy in suppressing genital herpes in immunocompetent patients, but similar therapy for labial herpes has not been tested in controlled trials. This randomized crossover trial evaluated …

Long-term therapy with disopyramide phosphate: Side effects and effectiveness

In this study, the safety and efficacy of long-term therapy with disopyramide phosphate were evaluated in 40 patients with documented, recurrent, symptomatic tachyarrhythmias. Twenty-one (53%) of the patients had organic heart disease, and nine of these patients had compensated congestive heart failure. The tachyarrhythmias which were treated were paroxysmal supraventricular tachycardia (21 patients), paroxysmal atrial fibrillation (six patients), and paroxysmal ventricular tachycardia (13 patients). In each patient there was evidence, from continuous ECG monitoring or electrophysiologic testing, that disopyramide would be effective therapy, and each patient was able to tolerate disopyramide (no side effects or tolerable side effects) during an initial trial period of 1 to 2 weeks. Dosages of disopyramide were 400 to 1600 mg/day (994 ± 320 mm/day). During long-term therapy, side effects were reported by 28 (70%) of the patients. The side effects were usually anticholinergic, and were usually a continuation of side effects noted during the initial trial period. None of the patients had idiosyncratic reactions to disopyramide. Most of the patients found side effects to be tolerable; however, in seven patients it was necessary to discontinue disopyramide after 1 to 8 (6 ± 3) months. Actuarial incidence of intolerable side effects was 21 ± 7% at 12 months. Nine (22%) of the 40 patients had symptomatic recurrences of tachyarrhythmia after 3 to 32 (15 ± 9) months of therapy. Actuarial incidence of drug ineffectiveness was 32 ± 10% at 24 months. Disopyramide was both effective and tolerated in 24 (60%) of the patients, who were followed for 2 to 64 (23 ± 16) months. In conclusion, it is feasible to use oral disopyramide phosphate as long-term therapy for patients with symptomatic tachyarrhythmias. Anticholinergic side effects, although common, are usually tolerated.