Safety Of High-dose Dexamethasone Research Articles

High-Dose Dexamethasone Versus Tocilizumab in Moderate to Severe COVID-19 Pneumonia: A Randomized Controlled Trial.

Background and objectivesRecent randomized controlled trials (RCTs) have indicated potential therapeutic benefits with high-dose dexamethasone (HDD) or tocilizumab (TCZ) plus standard care in moderate to severe coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS). No study has compared these two against each other. We aimed to compare the efficacy and safety of HDD against TCZ in moderate to severe COVID-ARDS.MethodsPatients admitted with moderate to severe COVID-19 ARDS with clinical worsening within 48 hours of standard care were randomly assigned to receive either HDD or TCZ plus standard care. The primary outcome was ventilator-free days (VFDs) at 28 days. The main secondary outcomes were 28-day all-cause mortality and the incidence of adverse events. Our initial plan was to perform an interim analysis of the first 42 patients.ResultsVFDs were significantly lower in the HDD arm (median difference: 28 days; 95% confidence interval (CI): 19.35-36.65; Cohen’s d = 1.14;p < 0.001). We stopped the trial at the first interim analysis due to high 28-day mortality in the HDD arm (relative risk (RR) of death: 6.5; p = 0.007; NNT (harm) = 1.91). The incidence of secondary infections was also significantly high in the HDD arm (RR: 5.5; p = 0.015; NNT (harm) = 2.33).ConclusionsIn our study population, HDD was associated with a very high rate of mortality and adverse events. We would not recommend HDD to mitigate the cytokine storm in moderate to severe COVID-19 ARDS. TCZ appears to be a much better and safer alternative.

Recombinant Human Thrombopoietin (rhTPO) and High-Dose Dexamethasone (HD-DXM) Versus High-Dose Dexamethasone Monotherapy As Frontline Treatment in Newly Diagnosed Adult Immune Thrombocytopenia (ITP): a Prospective, Multicentre, Randomised, Controlled Trial

Introduction: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia and caused by immune-mediated platelet destruction and impaired platelet production. Corticosteroids are recommended as the standard first-line treatment. As the immunosuppressive therapy,HD-DXM could decrease platelet destruction by regulating T cell immune abnormalities. Thrombopoietin (TPO) is the primary regulator of thrombopoiesis. Several studies have proved that TPO have profound effects on megakaryocyte development and platelet production as well as restore immune tolerance. We suppose the rhTPO and HD-DXM could work synergistically based on these mechanisms. Recently, several pilot studies have examined the efficacy and safety of TPO-RA in treatment-naive adult ITP patients. We present the results of the first prospective,multicenter,randomized,controlled trial on the largest cohort to date comparing the efficacy and safety of HD-DXM plus rhTPO vs HD-DXM as frontline therapy in newly diagnosed adult primary ITP patients.Methods: Between July 2013 and December 2016, 245 newly-diagnosed, treatment-naive ITP patients aged 18-75 years in 25 separate centers in China were enrolled in the trial (NCT01734044). DXM was administered orally at 40 mg daily for 4 consecutive days to both arms. The 4-day course of dexamethasone was repeated on days 11 to 14 in the case of lack of response. Patients in the experimental arm received subcutaneously rhTPO at a daily dose of 300U/kg concomitantly during the first 14 days. Patients with platelet counts higher than 100×109/L or more than 50×109/L increase of the baseline platelet count could discontinue the rhTPO treatments. Use of rescue treatments such as platelet transfusion and hemostatic agents were allowed at the discretion of the investigator if the platelet count <10×109/L or ≥10×109/L with active bleeding and were recorded. Patients were assessed at day 14. Study visits were scheduled every 1 month until the end of the 6th month or day of relapse. The primary endpoint was the early response rates at day 14 (OR: platelet count ≥30×109/L and at least 2-fold increase of the baseline platelet count and absence of bleeding, CR: platelet count ≥100×109/L). Key secondary endpoints were rates of sustain response and complete response at the end of month 6, duration of response (DOR), bleeding scores, assessments of adverse events (AEs). Any administration of additional ITP specific medication or withdrawn from the study because of no response was regarded as nonresponders.Results: 196 patients were randomly to receive HD-DXM with (n=100) or without (n=96) rhTPO. Demographics and baseline characteristics were balanced between the 2 arms. HD-DXM+ rhTPO resulted in a higher incidence of early OR at day 14 compared with HD-DXM monotherapy (89.0% vs 66.7%, P<0.001, table 1), the CR rate were 75.0% (HD-DXM+ rhTPO) vs 42.7% (HD-DXM) (P<0.001). Sustained OR and CR at the end of the 6th month was also higher in patients treated with HD-DXM+ rhTPO than in those treated with HD-DXM alone (OR: 51.0% vs 36.5%, P=0.022; CR: 46.0% vs 32.3%, P=0.043, table 1). Throughout the follow-up period, overall duration of response was greater in the experimental group, estimated by the Kaplan-Meier analysis (Figure 1, P=0.04). There was no difference between these 2 groups in terms of TTR, bleeding scores and rescue treatments. No statistically significant differences were observed in the incidence of treatment-related AEs between the two groups. Three patients had grade 4 or higher AEs in the HD-DXM+ rhTPO group, including early cerebral hemorrhage (n=2) and cerebral infarction (n=1); none were deemed treatment-related, one patient in the rhTPO group died of early cerebral hemorrhage. No patient was tested positive for neutralizing antibodies against TPO.Conclusions: Our findings suggest that the addition of rhTPO to HD-DXM is superior to HD-DXM monotherapy in the treatment of newly diagnosed treatment-naive adult ITP patients. Thus, this combination can be a feasible frontline therapy in adult ITP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical efficacy of high-dose dexamethasone with sequential prednisone maintenance therapy for newly diagnosed adult immune thrombocytopenia in a real-world setting.

ObjectiveAs first-line treatments for newly diagnosed adult immune thrombocytopenia (ITP), high-dose dexamethasone (HD-DXM) and conventional-dose prednisone achieve good initial responses, but their long-term efficacy is poor. To improve the long-term outcome of newly diagnosed ITP, we explored the efficacy and safety of HD-DXM with sequential prednisone maintenance therapy.MethodsThis retrospective study in a real-world setting assessed 72 consecutive newly diagnosed ITP patients administered first-line HD-DXM with sequential prednisone maintenance therapy from 1 June 2016 to 31 December 2019.ResultsSeventy patients obtained response (97.2%), and 55 achieved sustained response (SR) (76.4%). Fifty-three obtained complete remission (CR) (73.6%), and 39 achieved continuous CR at 6 months (54.2%). Among 36 anti-nuclear antibody-positive patients, 100% achieved response, and 28 achieved CR (77.8%). Among 24 antithyroid antibody-positive patients, 23 (95.8%) achieved response, and 20 achieved CR (83.3%). For patients with initial response, the 12-month probability of SR was 78.6%. For patients with initial CR, the 12-month probability of continuous CR was 64.2%. At 12 months, 21.4% of patients with initial response and 11.3% of patients with initial CR showed loss of treatment response.ConclusionsHD-DXM with sequential prednisone as the first-line treatment for newly diagnosed ITP patients may achieve good clinical efficacy.

Combination of ATRA and High-Dose Dexamethasone As First-Line Treatment in Adult Immune Thrombocytopenia:a Randomized, Phase 2, Open-Label Trial

Introductions Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by immune-mediated platelet destruction and impaired platelet production. As the immunosuppressive therapy, high-dose dexamethasone (HD-DXM) has been recommended as the standard first-line treatment. Nevertheless, approximately half of ITP patients relapse within 6 months and require further therapies. All-trans retinoic acid (ATRA) is a derivative of vitamin A that has an immunomodulatory effect on hemopoiesis. Our previous study demonstrated that ATRA could induce a more rapid and long-lasting response in patients with corticosteroid-resistant or relapsed ITP (Lancet haematology, 2017). In addition, we found that ATRA corrected impaired platelet production by regulating the complement-IL-1β loop and TNFAIP3/NF-κB/SMAD7 signaling pathway in ITP (Br J Haematol, 2018; Haematologica, 2019). These findings suggested that the addition of ATRA to HD-DXM in treatment-naive patients could improve sustained response rate based on the synergetic function. Here, we present the results of the first prospective, multicenter, randomized, controlled trial with the largest cohort to date comparing the efficacy and safety of HD-DXM plus ATRA vs HD-DXM as first-line therapy in newly diagnosed adult primary ITP patients. Methods In this open-label, randomized, phase 2 trial, we enrolled adult ITP patients from 6 different tertiary medical centers in China. Eligible subjects had confirmed newly-diagnosed, treatment-naive ITP; platelet counts &amp;lt;30×109/L or platelet counts &amp;lt; 50×109/L and significant bleeding symptoms (WHO bleeding scale 2 or above).Eligible patients were randomly assigned 1:1 with an interactive web-based response system to receive either oral ATRA (10 mg twice daily) plus HD-DXM or HD-DXM monotherapy for 12 weeks. DXM was administered orally at 40 mg daily for 4 consecutive days to both arms. The 4-day course of dexamethasone was repeated on days 11 to 14 in the case of lack of response by day 10(Figure 1). The primary endpoint was 6-month sustained response (SR) defined as platelet counts maintained &amp;gt; 50×109/L without any additional ITP-modifying therapy at the 6-month follow up. Key secondary endpoints were initial response by day 14 (OR: platelet count ≥30×109/L and at least 2-fold increase of the baseline platelet count and absence of bleeding; CR: platelet count ≥100×109/L), duration of response (DOR), bleeding scores, and adverse events (AEs). Results Between June 2015, and July 2018, 300 patients were randomly allocated into either ATRA plus HD-DXM (n=150) or HD-DXM monotherapy (n=150). At the 6-month follow-up, the proportion of patients with SR was significantly higher in the ATRA plus HD-DXM group than in the HD-DXM monotherapy group (61% vs 37%, p= 0.009). So far, the increase of almost one quarter is very encouraging. The combination of ATRA and HD-DXM resulted in a higher incidence of early OR at day 14 compared with HD-DXM monotherapy (83% vs 67%, P=0.031), and the CR rate was 60.0% (ATRA+HD-DXM) vs 40.6% (HD-DXM) (P=0.015). Throughout the follow-up period, overall DOR was greater in the combination group, estimated by the Kaplan-Meier analysis. Fewer patients in the combination group than in the monotherapy group relapsed during follow-up (p&amp;lt; 0.001), and the median time to relapse was 75 days (ATRA+HD-DXM) vs 48 days (HD-DXM). Bleeding was more effectively controlled in the ATRA plus HD-DXM arm, with fewer bleeding events and lower bleeding scores. There was no difference between the 2 groups in terms of rescue treatments. All subjects tolerated the treatment well, and no grade 4 adverse events or treatment-related death were reported. No statistically significant differences were observed in the incidence of treatment-related AEs between the two groups. Conclusions ATRA plus HD-DXM is an effective and safe treatment for ITP as a first-line therapy that can provide a sustained prolonged response in adults. This therapy could be a new treatment option for ITP subjects. Disclosures No relevant conflicts of interest to declare.

High-Dose Dexamethasone (HD-DXM) Plus Oseltamivir Versus High-Dose Dexamethasone for Treatment of Adult Primary Immune Thrombocytopenia: Interim Analysis of a Prospective, Multicenter, Randomized, Controlled Trial

Introduction: Primary immune thrombocytopenia (ITP) is an acquired hemorrhagic disorder caused by immune-mediated platelet destruction and insufficient platelet production. As the first-line treatment of ITP, corticosteroids enable the recovery of platelet count in 60% to 80% of cases. However, a large proportion of patients would relapse during steroid tapering or withdrawal. Recently, sporadic studies reported successful treatment of ITP with oseltamivir which decreased platelet destruction through inhibition of platelet desialylation, a possible mechanism leading to Fc-independent platelet phagocytosis by hepatocytes. We hypothesize that corticosteroids and oseltamivir might complement each other in terms of mechanisms and induce a better response in ITP. Therefore, a prospective randomized controlled trial was conducted to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus oseltamivir with HD-DXM monotherapy in adult ITP. Here we report the interim analysis of this study. Methods: From February 2016 to May 2018, 80 newly diagnosed treatment-naïve ITP patients from 5 tertiary medical centers in China were screened in the trial (NCT01965626). Dexamethasone was administered orally at 40 mg daily to both arms for 4 days (days 1 - 4). If platelet counts remained &amp;lt; 30 × 109/L or there were bleeding symptoms by day 10, another course of HD-DXM was given (days 11 -14). For the combination arm, oral oseltamivir was given concomitantly at a dosage of 75 mg twice daily for the first 10 days (days 1 - 10). The primary endpoints were initial response and sustained response (SR). Platelet counts should be confirmed on two separate occasions at least 7 days apart when defining responses (CR: platelet count ≥ 100×109/L and absence of bleeding; R: platelet count ≥ 30 × 109/L but &amp;lt; 100 × 109/L and at least a doubling of baseline and absence of bleeding). Initial responses were assessed by day 14. Responders underwent follow-up for at least 12 months or until relapse. Response lasting for at least 6 consecutive months without additional ITP-specific intervention was regarded as SR. Secondary endpoints included time to response (TTR), bleeding scores, duration of response and adverse events (AEs). Platelet transfusion was permitted in patients with severe bleeding symptoms and recorded. Requirements for any additional ITP-specific intervention were considered as treatment failure. Results: Fifty-nine patients were enrolled, of whom 28 were randomly to receive HD-DXM plus oseltamivir and 31 to HD-DXM monotherapy. Demographics and baseline characteristics were balanced between the 2 arms (Table 1). Results showed that HD-DXM plus oseltamivir achieved a higher incidence of initial response than HD-DXM alone at day 14 (82.1% vs. 58.1%, P = 0.045). At the end of 6 months, SR rate in the HD-DXM plus oseltamivir arm was higher than that in the HD-DXM monotherapy arm even though it did not reach statistical significance (42.8% vs. 25.8%, P = 0.167). Relapse-free survival in the HD-DXM plus oseltamivir arm was significantly improved compared with the HD-DXM monotherapy arm during follow-up period (HR 1.96, Log Rank P =0.043), as estimated by the Kaplan-Meier analysis. There was no statistical difference in median TTR between the two arms (P &amp;gt; 0.05). Bleeding was well controlled in both arms, with comparable post-treatment bleeding events (7.1% vs.19.3%, P&amp;gt; 0.05) and lower bleeding scores in the HD-DXM plus oseltamivir arm (0 vs. 0, P = 0.036). Incidence of AEs was similar between the 2 arms (P &amp;gt; 0.05). A slight increase in gastrointestinal reactions was observed in the HD-DXM plus oseltamivir arm but it did not reach statistical significance. Most of the AEs were mild to moderate (grade 1 to 2) and usually resolved spontaneously after medication was completed. No previously undescribed AEs was observed. Conclusions: The combination of HD-DXM with oseltamivir significantly improved the initial response in newly diagnosed ITP patients. However, due to the limitation of sample size, the conclusion of SR superiority can hardly be drawn at the moment. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Oseltamivir, a sialidase inhibitor which is extensively used in the treatment of or prophylaxis against influenza virus A and B. It has been reported that the treatment of oseltamivir could concomitantly increase platelet counts, which was independent whether influenza was diagnosed. Along those lines, several studies showed successful treatment of ITP patients with oseltamivir. We hypothesize that HD-DXM and oseltamivir might complement each other in terms of the mechanisms and achieve better response rates in ITP patients.

Clinical Efficacy and Safety of High-Dose Dexamethasone Plus Low-Dose Rituximab as First-Line Therapy in Newly Diagnosed Primary Immune Thrombocytopenia.

Standard-dose prednisone as first-line therapy for primary immune thrombocytopenia (ITP) can not obtain high long-term responses. Results from high-dose dexamethasone course administered in adult newly diagnosed ITP were promising. The role of standard-dose rituximab in first-line treatment of newly diagnosed ITP were also investigated. We retrospectively analyzed the efficacy and safety of high-dose dexamethasone plus low-dose (100mg/w) rituximab for treatment of adults newly diagnosed ITP. A total of eighteen patients received dexamethasone 40mg/day for 4 consecutive days (days + 1 to + 4), rituximab 100mg once weekly for a total of 4weeks (days + 7, + 14, + 21 and + 28). Non-responders accepted the repeated dexamethasone treatment every 2weeks for a total of up to 3 treatment cycles. The overall response was 100% at 28th day. Median follow-up was 17months (1-33months). Six patients (33.3%) relapsed. Sustained complete response or response after 6months and 12months of follow-up were reached in 83.3% (15/18) and 61.5% (8/13) of patients respectively. The 12-month and 15-month cumulative relapse-free survival were 69.3% and 60.7%. Incidence of adverse effects was 11.1% (2/18). High-dose dexamethasone plus low-dose rituximab therapy had high efficacy and well tolerability as first-line treatment option in newly diagnosed ITP.

High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83.Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.

Analysis of high-dose dexamethasone in different cycles on efficacy and safety of newly diagnosed ITP

To compare the efficacy and safety of high-dose dexamethasone in treating new-diagnosed primary immune thrombocytopenia (ITP) in monocycle, di-cycle, tri-cycle. Divided by the ratio of 1:1:1, 93 newly diagnosed patients were randomly accepted monocycle (Group A:dexamethasone 40 mg once a day, from day1 to day4), dicycle (Group B:dexamethasone 40 mg once a day, from day 1 to day 4, day 15 to day 18), tri-cycle (Group C:dexamethasone 40 mg once a day, from day 1 to day 4, day 15 to day 18, day 29 to day 32) of high-dose dexamethasone treatment. Its efficacy and safety on the patients in three groups were compared. Ninety-three newly patients with new-diagnosed ITP were divided into Group A, B, and C, 31 patients in each group. In terms of short-term benefits, there was no statistically significant difference among the 7th and 14th day complete response rate after end of treatment. However, there was statistically significant difference after the end of treatment on the 7th day response rate (41.9% vs 70.0% vs 90.0%, P<0.01) and the 14th day response rate (16.1% vs 36.70% vs 63.3%, P< 0.01); in terms of long-term benefits, there was no statistically significant difference among the 120-day response rate, the complete response rate within the treatment on the 60th, 90th and 120th day and the relapse rate at 90th and 120th day; however, there was statistically significant difference among the 60- day response rate (10.0% vs 26.6% vs 53.3%, P<0.01), 90-day(0.0% vs 13.3% vs 30.0%, P<0.01) and 60-day relapse rate(88.9% vs 73.3% vs 46.7%, P<0.01). Mostly of the treatment-related adverse reactions in the three groups were mild, and most patients are tolerable. Although the complete response rate of ITP patients did not improved by increasing the cycle of high-dose dexamethasone, but improved response rate in three months, and adverse reactions were tolerable, which could be used as a reference for clinical use.

大剂量地塞米松联合重组人血小板生成素治疗48例成人初治重症原发免疫性血小板减少症的有效性及安全性

目的评价大剂量地塞米松联合重组人血小板生成素(rhTPO)治疗成人初治重症原发免疫性血小板减少症(ITP)的有效性及安全性。方法48例初治重症ITP患者，男26例，女22例，中位年龄45(20~69)岁，随机分为观察组(23例)和对照组(25例)，分别给予大剂量地塞米松(40 mg/d×4 d)联合rhTPO(15 000 U/d×14 d)方案及大剂量地塞米松单药治疗。比较两组患者治疗后血小板计数、血小板增幅以及总有效率，观察药物的不良反应。结果治疗第3、7、14、30天，观察组血小板计数及增幅均高于对照组(P<0.05)。治疗第3、7天，两组总有效率差异无统计学意义(34.8％对36.0%，χ2=0.008，P=0.930；56.5％对48.0%，χ2=0.349，P=0.555)；治疗第14、30天，观察组总有效率均高于对照组(91.3％对68.0%，χ2=3.945，P=0.047; 82.6％对52.0%，χ2=5.050，P=0.025)。观察组出现肌肉酸痛不适1例，停药后自行好转。结论与大剂量地塞米松单药比较，大剂量地塞米松联合rhTPO治疗成人初治重症ITP起效快速、血小板计数增幅较大、疗效持久，具有良好的安全性。

High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial

AbstractThis study compared the efficacy and safety of high-dose dexamethasone (HD-DXM) and conventional prednisone (PDN) on the largest cohort to date as first-line strategies for newly diagnosed adult primary immune thrombocytopenia (ITP). Patients enrolled were randomized to receive DXM 40 mg/d for 4 days (n = 95, nonresponders received an additional 4-day course of DXM) or prednisone 1.0 mg/kg daily for 4 weeks and then tapered (n = 97). One or 2 courses of HD-DXM resulted in a higher incidence of overall initial response (82.1% vs 67.4%, P = .044) and complete response (50.5% vs 26.8%, P = .001) compared with prednisone. Time to response was shorter in the HD-DXM arm (P < .001), and a baseline bleeding score ≥8 was associated with a decreased likelihood of initial response. Sustained response was achieved by 40.0% of patients in the HD-DXM arm and 41.2% in the PDN arm (P = .884). Initial complete response was a positive indicator of sustained response, whereas presence of antiplatelet autoantibodies was a negative indicator. HD-DXM was generally tolerated better. We concluded that HD-DXM could be a preferred corticosteroid strategy for first-line management of adult primary ITP. This study is registered at www.clinicaltrials.gov as #NCT01356511.

Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial

Introduction Oral prednisone (PDN) is conventional standard initial management for adult immune thrombocytopenia (ITP). In recent years single arm studies propose that high-dose dexamethasone (HD-DXM) improves response rate and remission duration and reduces adverse effects, though a randomized trial demonstrated no superiority of HD-DXM. It still lacks evidence-based conclusion on which one is better in efficacy and safety. We conducted a prospective randomized multicenter clinical trial to compare the efficacy and safety of HD-DXM and PDN as first-line strategy for adult newly diagnosed ITP.Methods We enrolled adult newly diagnosed ITP patients aging between 18 and 80 years, peripheral PLT count <30x109/L or with bleeding symptoms. Diagnosis of ITP and definition of newly diagnosed ITP followed international working group report and ASH evidence-based guideline. A 1:1 randomization was assigned between HD-DXM and PDN arm. In HD-DXM arm, dexamethasone was administered orally at 40mg/d for 4 consecutive days. If PLT count remained or dropped below 30x109/L by day 10, another four-day course of HD-DXM was given. Patients received prednisone orally at 1.0mg/kg/d for no more than 28 days in PDN arm, and then tapered rapidly to minimized maintenance dosage of <15mg/d in responders or stop in non-responders. Early response was evaluated according to criteria mentioned above. We defined sustained response as PLT count maintaining above 30x109/L for 6 months or more. Responders underwent follow-up for at least 6 months or until relapse. Adverse effects were recorded for analysis of safety. Informed consent was obtained from all enrolled patients in accordance with the Declaration of Helsinki. This study was approved by Ethics Committee of each participating site and registered at http://clinicaltrials.gov/ as NCT01356511.Results From Jan 2011 to May 2014, 182 newly diagnosed adult patients were enrolled from 9 sites over Shandong Province, China, with 92 randomized to HD-DXM arm (62 females and 30 males; age median 43, range 18~73 years) and 90 to PDN arm (68 females and 22 males; age median 44.5, range 18~76 years). Baseline PLT count were 8.93±8.19 (HD-DXM arm) and 10.60±8.67 (PDN arm) x109/L, respectively. Overall response rate in HD-DXM arm was 84.8% (78/92) with 52.2% (48/92) CR, while in PDN arm 74.4% (67/90) and 28.9% (26/90). HD-DXM arm showed similar overall response (P=0.099) but higher CR rate (P=0.002). HD-DXM arm also demonstrated shorter time to response (3.21±1.35 vs. 5.97±4.28 days, P=0.001). 149 patients were available for evaluation of sustained response, 76 in HD-DXM arm and 73 in PDN arm, with follow-up of a median of 10(1-40) and 12(1-39) months, respectively. There was no statistically significant difference between the two arms in sustained response rate (39.5% vs. 49.3%, P=0.251). Generally both treatments were well tolerated. Adverse effects were recorded (HD-DXM/PDN), including hyperglycemia (3/5), hypertension (3/3), peptic ulcer (1/3), gaining weight (0/4), and infection trend (0/2).Conclusion One or two courses of HD-DXM demonstrated higher CR rate and shorter time to response than PDN. HD-DXM could be a better first-line choice for adult ITP.Table 1Characteristics of patients in HD-DXM and PDN armParameterHD-DXMPDNNo. of patients9290Age, median (range)43 (18 - 73)44.5 (18 - 76)Gender, female/male62/3068/22Baseline platelet count, x109/L8.93±8.1910.60±8.67 DisclosuresNo relevant conflicts of interest to declare.

First-LINE Treatment With High-Dose Dexamethasone Terapy For Adult Primary Inmune Thrombocytopenia

▪ IntroductionPrimary immune thrombocytopenia (ITP) is an acquired autoimmune disorder with a very variable outcome. Bleeding manifestations and platelets count are considered the main criteria to start treatment in these patients. The initial recommended therapy are corticosteroids and intravenous immunoglobulin (IgsIV). The aim of our study is the description of efficacy and safety of high-dose dexamethasone (Dx) used as frontline therapy in newly diagnosed ITP patients. MethodsA series of patients diagnosed in our centre from March 2009 to August 2012 has been studied. They have received first-line treatment with Dx (40 mg/d four consecutive days every 2 or 4 weeks) for 1 to 6 courses. Sex, age, cardiovascular risk factors, reasons to treat, response, courses of treatment, complications and relapse rate were recorded and analyzed. ResultsOur series of twenty-nine patients, 18 women (62%) and 11 men (38%), had a median age of 54 years (range 16-92 years). Twenty-five patients (86%) were treated after low platelet counts (30x 10e9 / L) with or without clinical bleeding, whereas the other four patients were treated as a surgery preparation. One patient received a reduced dose of Dx (20 mg/d x 4 days) because of comorbidities and high risk of infection. In thirteen patients, IgsIV were added to Dx in the first course (1g/kg/d x 2 days), because of high bleeding risk or more severe bleeding at diagnosis. Platelets count at baseline was 15x109/ L (range 1-29 x109/ L). Ninety-three percent of patients responded after the first course of Dx (69% complete response CR, 24% partial response PR), and 45% of the patients did not require additional Dx treatment. The median time to reach a response was 5 days since the first day of treatment (range 2-60).The sixteen patients who need more than one course received a median of 4 (range 2-10), all of them without IgsIV. After a median follow-up of 14 months (range 2-45), 69% of these patients maintained the response without further treatment. Therefore, the overall response of the series reaches 83%.After 6 courses of treatment, 5 subjects did not achieved response and were classify as corticosteroid dependent. Of these, one patient was splenectomized and at present he remains at CR after 30 months of follow up. Another patient is waiting for splenectomy, and other three received thrombopoietin analogs, remaining all them in CR under treatment.Thirteen patients received a combination of Igs and Dx in the first course due to high risk of bleeding (platelets less than 20 x 10e9/L and hemorrhagic manifestations). Eleven of them (81%) achieved response (4 PR, 7CR) at a median time of 4 days (range 2–60). After the first course of treatment, 61% (8 of 13) of patients receiving both IgsIV and Dx responded, vs 35% (5 of 16) of those treated only with Dx. This difference was not statistically significant, probably because of the small number of patients in our series. All patients treated with IgsIV and Dx in the first course got the best response after 4 cycles of dexamethasone, compared to 75% of subjects treated with Dx for 4 to 6 courses.Dx was usually well tolerated, since only 13% of the patients experienced side effects: one case of hypertension, another patient developed hyperglycemia associated to corticosteroids and other two presented mild transient steroid psychosis episodes. Infectious events were not observed. ConclusionsTreatment with high-dose dexamethasone as first-line treatment for ITP is a good alternative to prednisone because it shows a high efficacy and a good safety profile. In our experience, the association of IgsIV and Dx in the first course may improve the response rate and decrease the total dose of steroids needed to achieve a similar response. Disclosures:No relevant conflicts of interest to declare.

Antiemetic efficacy of high-dose dexamethasone: randomized, double-blind, crossover study with high-dose metoclopramide in patients receiving cancer chemotherapy

A double-blind, randomized, crossover study was conducted to compare the efficacy and safety of high-dose dexamethasone and high-dose metoclopramide in the treatment of chemotherapy-induced nausea and vomiting. All entered patients had no prior chemotherapy and all received inpatient emetogenic chemotherapy mainly without cisplatin. Of the 40 evaluable patients, 23 (58%) had no vomiting with dexamethasone compared with only 11 (28%) receiving metoclopramide ( P < 0.025). Dexamethasone was found to have less adverse effect than metoclopramide on patient's appetite and activity ( P < 0.025 and P < 0.01, respectively). Twenty-one patients (53%) developed mild to severe somnolence with metoclopramide compared to only seven (18%) who experienced this adverse effect with dexamethasone ( P < 0.01). Six patients (15%) developed extrapyramidal manifestations with metoclopramide, but none with dexamethanesone. Furthermore, during dexamethasone therapy, patients developed less diaphoresis, insomnia, headache and dizziness. Upon questioning patients about their preference to future use of the antiemetic drug therapy, 28 patients (70%) preferred dexamethasone, two (5%) preferred metoclopramide and 10 (25%) found no difference. We conclude that high-dose dexamethasone has a greater antiemetic activity and is more safe than high-dose metoclopramide in patients receiving emetogenic chemotherapy mainly without cisplatin.