Efficacy and Safety of Peg-Interferon-α2a In Myelofibrosis: a Study of the FIM and GEM French Cooperative Groups

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4103-4103 ◽  
Author(s):  
Jean-Christophe Ianotto ◽  
Françoise Boyer-Perrard ◽  
Jean-Loup Demory ◽  
Jerome Rey ◽  
Lydia Roy ◽  
...  
Keyword(s):  
Observational Study ◽  
Low Dose ◽  
Therapeutic Option ◽  
Complete Response ◽  
Dose Schedule ◽  
Off Label Use ◽  
Off Label ◽  
Small Series ◽  
Interferon Α2a ◽  
Label Use

Abstract Abstract 4103 Background: The moderate effect of most palliative treatments in primary and secondary myelofibrosis (MF), in addition to the limited possibilities of allogeneic stem cell transplantation, has incited physicians to look for alternative treatments. Since 1987, several studies have suggested that interferon may be beneficial in the treatment of MF. However, important hematological and general limiting toxicities frequently occur in MF patients (pts), leading to rapid treatment discontinuation in more than 50% of pts. Better results were recently reported in a small series of 13 MF pts treated with Peg-Interferon-α2a (Ianotto et al., Br J Haematol, 2009). The present study aimed to collect data of pts with primary and secondary MF treated with Peg-Interferon-α2a in French centers members of the FIM (French Intergroup of Myeloproliferative disorders) and GEM (Groupe d'Etudes des Myelofibroses) groups, to better assess tolerance and efficacy of this form of interferon in MF. Patients and Methods: Between Dec 2006 and Feb 2010, 39 MF pts treated with Peg-Interferon-α2a were registered from 10 different French centers affiliated to FIM and GEM groups. Age of pts ranged from 41 to 81 years, 21 were men and 18 women. Sixteen pts had primary MF, 13 had post-PV and 10 post-ET MF, respectively. Twenty-five patients (64%) were JAK2V617F positive. Twenty-eight patients had previously received other cytoreductive treatment. Clinical and biological parameters were collected at diagnosis and every 3 months. Responses were assessed according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Analyses were performed in July 2010, after a median follow-up of 18 months (range: 3 – 42 months). Results: Among the 28 patients with splenomegaly, we observed 10 responses (36%) including 7 complete and 3 partial responses. Fourteen patients had constitutional symptoms which resolved in 8 of them (57%). Seven of 15 patients (47%) with an initial hemoglobin level below 100 g/L achieved complete response (CR). Three of 8 (37%) transfused pts became transfusion-independent. Twenty-two patients had abnormal WBC count which normalized in 13 of them (59%). Platelet count was abnormal in 27 patients, and 14 (52%) achieved CR with Peg-Interferon-α2a treatment. The evolution of the JAK2V617F allele burden is currently under investigation and will be presented at the meeting. The initial median dose of Peg-Interferon-α2a effectively received was 103 μ g/wk, further decreased to a median of 85 μ g/wk after one year. At time of analysis, treatment was stopped in 11/39 (28%) pts due to side effects, inefficacy or hematologic evolution. Conclusion: In this observational study, we found higher efficacy and better tolerance of interferon than previously reported in patients with primary or secondary MF. Such results were possibly due to a better tolerance of the pegylated form used, and to the low-dose schedule applied by the physicians. Our results suggest at least that Peg-Interferon-α2a should be considered as a possible therapeutic option in selected MF patients. Future clinical trials in MF will hopefully involve combinations of low dose Peg-Interferon-α2a with JAK2-inhibitors or immunomodulatory agents in order to improve tolerability and increase efficacy. Disclosures: Off Label Use: This is an observational study of the off-label use of peg-Interferon-alfa2a in myelofibrosis.

Off-label use of inhaled bronchodilators in hospitalised patients in Spain: a multicentre observational study

2020 ◽  
pp. ejhpharm-2019-002171
Author(s):  
Elena Villamañán ◽  
Carmen Sobrino ◽  
Cristina Bilbao ◽  
Jaime Fernández ◽  
Alicia Herrero ◽  
...  
Keyword(s):  
Observational Study ◽  
Off Label Use ◽  
Off Label ◽  
Hospitalised Patients ◽  
Label Use

Low Dose Azacitidine (AZA) Reduces the Incidence of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 742-742 ◽  
Author(s):  
Marcos de Lima ◽  
Simrit Parmar ◽  
Julianne J Chen ◽  
Sergio A Giralt ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Low Dose ◽  
Control Group ◽  
Cell Transplant ◽  
Off Label Use ◽  
Landmark Analysis ◽  
Off Label ◽  
Label Use

Abstract Abstract 742 AZA has immunomodulatory properties that may affect donor lymphocytes favorably, potentially leading to less GVHD after HSCT. We have been investigating low-dose AZA (32 mg/m2 daily for 5 days) to prevent AML/MDS relapse after HSCT. Interestingly, in our dose finding phase I study (Cancer, 2010) there was a suggestion of less cGVHD with longer AZA treatments. We then hypothesized that this approach leads to less cGVHD, and performed a comparison of patients that received AZA to prevent relapse versus historic controls that did not receive the drug. Major objective of this analysis is to determine the cumulative incidence of cGVHD with versus without AZA. Methods. Patients received AZA based on high risk of relapse disease, starting at a median of 45 days from transplant (range, 17–149). AZA effect on aGVHD was not studied since the drug was started after most cases of aGVHD had already occurred or/and had resolved or improved. Patients with active acute GVHD (aGVHD) were not eligible to receive AZA. Median dose was 32 mg/m2 (range, 8–40). Median number of AZA cycles was 3 (range, 1–54), and median time on AZA for patients that received >3 cycles (n=37) was 144 days (range, 93–1329). Using a computer algorithm, we randomly selected from our departmental database a control group consisting of patients who had received HSCT within the same time period, and had similar GVHD prophylaxis, stem cell source, and comparable low risk of grade II-IV aGVHD (Table). Two hundred and thirty patients were identified fulfilling these criteria. The rate of cGVHD was compared between the AZA group (grouped as 1–3 cycles and >3 cycles) and the control group, in a landmark analysis starting at 6 months after HSCT. Leukemia relapse or death in remission before cGVHD onset were considered as competing risks in this analysis. Results. Median follow-up was 25 months (range, 1–99) in the AZA group, and 31 months (range, 1.5–117) in the control group. 29, 24, and 115 patients in the >3 AZA cycles, 1–3 AZA cycles, and the control group were evaluable for the 6-month landmark analysis, respectively. The numbers of patients developing cGVHD and the HR at 2 years in this analysis were as follows: 53 of 115 controls (reference group), 11 of 24 patients who received 1–3 AZA cycles (HR at 2 years, 0.9; P=NS), and 6 of 29 patients who received >3 AZA cycles (HR at 2 years, 0.4; 95% confidence interval (CI), 0.1–0.8; P=0.02) developed cGVHD. Similarly, in a landmark analysis, the cumulative incidence of cGVHD was significantly lower in the subgroup that received >3 AZA cycles (figure). Conclusion. Low-dose AZA appears to reduce the likelihood of developing cGVHD. We are investigating if this effect is associated with preservation or improvement of the graft-versus-leukemia effect in an ongoing, randomized study. Disclosures: de Lima: Celgene: Research Funding. Off Label Use: azacitidine: off-label use as maintenance therapy following allogeneic stem cell transplant for MDS/AML. garcia Manero:celgene: Research Funding.

scholarly journals «Off-label» use of botulinic toxin type A preparations in neurological practice

2018 ◽  
Vol 20 (2) ◽  
pp. 195-201
Author(s):  
L R Akhmadeeva ◽  
Kh P Derevyanko
Keyword(s):  
Botulinum Toxin ◽  
Therapeutic Option ◽  
Botulinum Toxin Type A ◽  
Case Series ◽  
Type A ◽  
Botulinum Toxin Type ◽  
Off Label Use ◽  
Off Label ◽  
Positive Effects ◽  
Label Use

The modern view on the application of botulinum toxin type A for the off-label use in neurology and foreign experience analysis are presented. The «off-label» category referred to any prescription of a medication in case of using it for unregistered indications, with product instruction violation or in the presence of contraindications including age restrictions. The sources of information about medicines were the leaflets of manufacturers of medicines and the State Register of Medicines. It is well known that Botulinum toxin type A is a good therapeutic option for treating children with cerebral palsy. Increased efficacy of regularly repeated cycles with Onabotulinumtoxin A in medication-overuse headache patients beyond the first year of treatment. Botulinum toxin type A is effective in the management of sialorrhea. Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. Facing depression with botulinum toxin: positive effects on mood have been observed in subjects who underwent treatment of glabellar frown lines with botulinum toxin and, in an open case series, depression remitted or improved after such a treatment. Botox injection significantly improved foot dystonia, pain and lower limb functional outcomes in patients with Parkinson’s disease with deep brain stimulation. The paper describes the problems associated with the lack of clinical data about the possibility of using botulinum toxin type A in different conditions, emphasizes the need to organize clinical trials and educational programs for neurologists as well as more active implementation of protocols for the treatment of patients.

Human Chorionic Gonadotropin Hormone Induces Indoleamine 2,3-Dioxygenase and Interleukin-10 Expression In Patients With Graft-Versus-Host-Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 911-911
Author(s):  
Ahmet H. Elmaagacli ◽  
Markus Ditschkowski ◽  
Nina-Kristin Steckel ◽  
Hellmut Ottinger ◽  
Uwe Hillen ◽  
...  
Keyword(s):  
Low Dose ◽  
Chronic Gvhd ◽  
Interleukin 10 ◽  
Off Label Use ◽  
Graft Versus Host ◽  
Off Label ◽  
Human Chorionic Gonadotropin Hormone ◽  
Hcg Therapy ◽  
Severe Grade ◽  
Label Use

Abstract Background Chronic graft-versus-host disease (GVHD) is a major complication following allogeneic hematopoietic stem cell transplantation and is associated with a substantial morbidity and mortality. It is a systemic inflammatory disorder that reflects the lack of immune tolerance between donor-derived immune competent cells and host organs. Human chorionic gonadotropin hormone (hCG) is a natural occurring hormone during pregnancy secreted by syncytiotrophoblasts of the placenta. We had previously observed (Koldehoff et al; J Leukoc Biol 2011) that the rejection of transplanted skin was significantly delayed by hCG in a mouse skin transplant model and had also demonstrated that tryptophan-catabolizing enzyme, indoleamine-2,3-dioxygenase(IDO), interleukin-10 (IL 10) and T-regulatory cells (Tregs) increased significantly in females treated with hCG as preconditioning therapy for in-vitro-fertilization. Since all these factors are known to induce tolerance and given the low rate of adverse effects, we off-label used low dose of hCG to treat 20 patients as forth- or fifth-line therapy with steroid-refractory or intolerant severe-grade chronic GVHD. Patients Because all of these factors are known to induce tolerance and given the low rate of adverse effects in preconditioning therapy, we off-label used low dose of hCG (187 IU) to treat 8 male and 12 female patients (median age 48, r. 28-68) with moderate or severe grade of chronic GVHD according to the NIH criteria; all patients had been informed of the experimental state of this treatment and provided written consent. Results The median number of sites of chronic GVHD involvement per patient was 3 (range, 1-6). hCG therapy was started as 4 or 5th line-therapy together with preexisting medication with prednisone and a calcineurin inhibitor. Twelve of 20 patients (60%) had an objective partial response during 8 weeks of hCG treatment with at least 50% improvement according to the TSS score. Responses included softened skin and subcutaneous tissue; decreased erythema and extent of sclerodermatous, hidebound skin; improved joint mobility and gait; gastrointestinal improvements; and resolution of neuropathy. Nine patients had stable disease (6 with minor responses). Only one patient with previous ATG treatment showed progression of her liver GVHD (histologically proven) and died from GHVD. All other patients were well and alive. Daily low-dose hCG was well tolerated. Adverse events that were possibly related to hCG included reversible and asymptomatic CTCAE grade 4 hypertriglyceridemia (n=1), grade 2 constitutional symptoms (fever, malaise, fatigue; flush, breast enlargement). IDO expression increased up to 8 times and IL10-serum level up to 2 times after 3 weeks of hCG therapy (p<0.003 and p<0.04). T-regulatory cell expansion was documented in 3 patients. Conclusion This successful use of hCG in an immune disorder warrants further studies to assess its role as an immunosuppressant in GVHD and potentially other autoimmune disorders. Disclosures: Off Label Use: The off-label use of HCG will be presented here for the first tiem for treatment of chronic GVHD and will clearly marked as off-label use.

scholarly journals Off-Label Medicine Use in Pediatric Inpatients: A Prospective Observational Study at a Tertiary Care Hospital in India

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Mohd Masnoon Saiyed ◽  
Tarachand Lalwani ◽  
Devang Rana
Keyword(s):  
Observational Study ◽  
Prospective Observational Study ◽  
Pediatric Patients ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Quality Data ◽  
Care Hospital ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

Background. In the absence of standard pediatric prescribing information, clinicians often use medicines in an off-label way. Many studies have been published across the globe reporting different rates of off-label use. There is currently no study based on Indian drug formulary.Methods. The prospective observational study included pediatric patients in ages between 0 and 12 years admitted in a tertiary care hospital. Off-label use was assessed using the National Formulary of India (NFI). Predictors of off-label use were determined by logistic regression.Results. Of the 1645 medications prescribed, 1152 (70%) were off-label based on 14 possible off-label categories. Off-label medicines were mainly due to dose difference and use in restricted age limits as indicated in NFI. Respiratory medicines (82%), anti-infectives (73%), and nervous system medicines (53%) had higher off-label use. Important predictors of off-label prescribing were pediatric patients in age of 0 to 2 years (OR 1.68, 95% CI;P<0.001) and hospital stay of six to 10 days (OR 1.91, 95% CI;P<0.001).Conclusion. Off-label prescribing is common among pediatric patients. There is need to generate more quality data on the safety and efficacy of off-label medicines to rationalize pediatric pharmacotherapy.

scholarly journals Low dose Rituximab for Preemptive Management of Thrombotic Thrombocytopenic Purpura ( TTP )

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5029-5029
Author(s):  
John C. Nelson
Keyword(s):  
Low Dose ◽  
Normal Values ◽  
Off Label Use ◽  
Off Label ◽  
Adamts13 Deficiency ◽  
Igg Deficiency ◽  
Autoimmune Cytopenias ◽  
Reported Data ◽  
Clinical Changes ◽  
Label Use

Abstract Low dose rituximab has been successful in treating some patients with autoimmune cytopenias. Recently reported data indicate preemptive rituximab may postpone hematologic relapses of TTP in patients with chronic severe ADAMTS13 deficiency. A now 22-year-old woman had multi-relapsing TTP with five episodes over the previous 10 years, three of which were successfully treated with four doses of rituximab 375 mg/m2. The most recent course in 2009 was given preemptively because intense ADAMTS13 monitoring had shown that previous hematologic relapses followed shortly after developing severe ADAMTS13 deficiency. Asymptomatic chronic IgG deficiency less than 300 mg% had followed this most recent rituximab course given in 2009. In 2014, continued intense ADAMTS13 monitering disclosed a new progressive decrease in ADAMTS13 levels from normal to severely deficient levels with a weak inhibitor, but no hematologic or clinical changes. Just two 100 mg rituximab doses have been followed by a progressive rise of ADAMTS13 levels to solidly normal values with significant improvement by day 13 post initiation and normalization by day 34. Low dose rituximab could be a viable alternative for preemptively managing TTP patients with persistently severly low ADAMTS13 levels. Disclosures Off Label Use: Off label use of rituximab to treat TTP.

Lenalidomide Administration in Heavily Pretreated Patients with Non Hodgkin Lymphoma – First Report of the REVEAL Study (REVlimid® Effectiveness of Administration in patients with Lymphoma)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4979-4979
Author(s):  
Luigi Rigacci ◽  
Francesco Zaja ◽  
Alberto Fabbri ◽  
Alice Di Rocco ◽  
Angelo Michele Carella ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hodgkin Lymphoma ◽  
Therapeutic Option ◽  
Stage Iv ◽  
Management Plan ◽  
Off Label Use ◽  
Off Label ◽  
Non Hodgkin Lymphoma ◽  
Heavily Pretreated ◽  
Label Use

Abstract Abstract 4979 Lenalidomide (Revlimid®) is an oral treatment authorized in the US and EU for use in relapse/refractory multiple myeloma. Since March 2008, lenalidomide, in combination with Dexamethasone, is marketed in Italy in the aforementioned indication. The Italian Drug Agency (AIFA) has also granted authorization for the off-label use of lenalidomide in patients with Non Hodgkin Lymphoma (NHL) who have no residual therapeutic option, provided these patients are tracked in a registry, in order to ensure their compliance with the Risk Management Plan (RMP) already in place for the multiple myeloma indication. The authorization was granted based on preliminary published favorable phase 2 data (Wiernik, 2008; Habermann, 2009). April 2008 to November 2010 lenalidomide was prescribed (following the 94/98 Italian law) to over 200 NHL patients, mainly diagnosed as Diffuse Large B Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL). This retrospective observational study was undertaken to gather clinic-pathological and laboratory data about this cohort of NHL patients, with the objective to evaluate the safety and the efficacy of lenalidomide administered, in the context of routine clinical practice, to a heavily pretreated patient population with no remaining therapeutic alternative. Also, efforts will be done in order to identify prognostic factors which can affect response to lenalidomide treatment. As of today, data on 30 patients treated at 6 sites have been collected and analyzed. Patient demographics and disease characteristics are summarized in Table 1. Patient median age was 70.5 years (range 36.0 – 90.0); median number of previous treatments was 5 (range 1 – 17). Over ninety three per cent (93.3%.) of the patients were previously treated with Rituximab. Forty per cent (40%) had DLBC histology, 16.7% MCL, 13.3% follicular histology and 16.7% were transformed lymphomas. As expected, 60% of the patients had stage IV disease, in keeping with the highly unfavorable characteristics of a heavily pretreated patient population. Responses were assessed according to the International Workshop on Lymphoma Response Criteria (IWRC). The number of lenalidomide cycles administered varied between 1 and 15 in this small patient group; 69.2% of the patients, evaluated at cycle 3, showed an objective response (OR). Table 1 TABLE T3 DEMOGRAPHIC CHARACTERISTICS (EVALUABLE POPULATION) Demographic and Disease Characteristics on evaluable population (N=30) Gender Male 20 (66.7%) Female 10 (33.3%) Age (years) N 30 Mean (SD) 69.8 (11.2) Median 70.5 Range 36.0- 90.0 Time since diagnosis (years) N 22 Mean (SD) 8.82 (8.3) Median 3.30 Range 0.45- 9.0 Histology DLBCL 40% Follicular 13.3% MCL 16.7% Transformed 16.7% Stage Stage III 20% Stage IV 60% Data on approximately 180 patients treated at 46 sites throughout Italy will be analysed and presented. Only subjects who refuse to make their data available for review and analysis, or are currently participating in an interventional clinical study (from the date of enrollment into the interventional study) will be excluded. Although very preliminary, this experience indicates that lenalidomide has interesting anti- lymphoma efficacy, even in patients who have exhausted all available therapeutic options. Disclosures: Off Label Use: The Italian Drug Agency (AIFA) has also granted authorization for the off-label use of lenalidomide in patients with Non Hodgkin Lymphoma (NHL) who have no residual therapeutic option, provided these patients are tracked in a registry, in order to ensure their compliance with the Risk Management Plan (RMP) already in place for the multiple myeloma indication.

Off-Label Drug Use in Pediatric Out-Patient Care: A Multi-Center Observational Study

2020 ◽  
pp. 001857872094222
Author(s):  
Aeshah AlAzmi ◽  
Zahra Alasmari ◽  
Consuela Yousef ◽  
Ahmed Alenazi ◽  
Mohammed AlOtaibi ◽  
...  
Keyword(s):  
Drug Use ◽  
Observational Study ◽  
Pediatric Population ◽  
Prescribing Patterns ◽  
Off Label Use ◽  
Kingdom Of Saudi Arabia ◽  
Off Label ◽  
High Incidence ◽  
Study Support ◽  
Label Use

Objective: Prescribing a drug for a child is not an easy task and requires using the best available evidence as a guide, especially when a drug is used off-label. The practice of prescribing a drug for off-label use is fairly widespread worldwide. The FDA does not regulate prescribing patterns or practices of individual practitioners and, therefore, allows off-label use. The main objective of this study is to evaluate off-label prescribing among the pediatric population in the Kingdom of Saudi Arabia (KSA). Method: This is a retrospective, simple random selection observational study of children (≤15 years) who visited pediatric clinics and had at least 1 drug prescribed over a 12-month period (January to December 2018). Results: A total of 865 drugs (mean 1 and SD 0.24) were prescribed to 326 children. Off-label was identified in 39.4% of the drugs with a frequency of 512 (as 1 drug may belong to more than 1 off-label category). The most common reason for off-label prescribing was related to doses that were “higher or lower than the recommended use” (48.6%), and the most frequently identified drug class prescribed for off-label use was anti-infective drugs for systemic use (39.9%). The percentage of off-label drug use was found to be higher in girls and in the age group of 1 month to 2 years ( P = .001) for both variables. In addition, a significant association was found between off label drug use and the total number of drugs prescribed, P < .001. Conclusion: The findings of this study showed a high incidence of off-label prescribing mainly related to dosing and indication. The results of this observational study support the need to establish a unified national pediatric dosing formulary guide to ensure safe drug use in pediatrics.

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