Anti-ADAMTS13 Inhibitor Boosting During Plasma Exchange Therapy in Acquired TTP Is the Expression of a General Dysregulation of the Immune Response,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3299-3299 ◽  
Author(s):  
Monica Schaller ◽  
Irmela Sulzer ◽  
Magnus Mansouri ◽  
MD student ◽  
Bernhard Lämmle ◽  
...  
Keyword(s):  
Immune Response ◽  
Platelet Count ◽  
Plasma Exchange ◽  
Strong Increase ◽  
Line Treatment ◽  
Adamts13 Activity ◽  
First Line ◽  
Antibody Titers ◽  
Inhibitor Titer ◽  
First Line Treatment

Abstract Abstract 3299 Background. Thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia with schistocytes on the peripheral blood smear and a variable degree of ischemic organ dysfunction due to microvascular thrombosis. In the case of acquired TTP, circulating autoantibodies inhibit ADAMTS13 activity and/or increase ADAMTS13 clearance. The first-line treatment of an acute TTP bout is plasma exchange (PEX) therapy with the replacement of fresh frozen plasma. Up to 30% of TTP patients show an exacerbation under PEX. After initial improvement, platelet counts drop again which is typically associated with a strong increase of ADAMTS13 inhibitor titers, and therefore the phenomenon is also referred to as inhibitor boosting. Interestingly it is apparently not seen in other autoimmune diseases treated with PEX, like acquired hemophilia A or myasthenia gravis. The aim of this study was therefore to investigate if inhibitor boosting in acquired TTP is a general or ADAMTS13 specific phenomenon. Methods. Plasma samples, obtained day-to-day during PEX therapy supplemented with steroids until remission, of 9 patients suffering from acute TTP due to severe acquired ADAMTS13 deficiency, were analyzed for the following laboratory parameters: (a) C-reactive protein (CRP) and total IgG, (b) ADAMTS13 activity, (c) anit-ADAMTS13 antibody titers by ELISA, (d) functional inhibitor titers by FRETS assay, and (e) anti-TG and anti-TPO antibody titers. Results. At initial presentation inhibitor titers ranged from 0.7 - >10 BU/ml (a positive functional inhibitor titer is defined as >0.4 BU/ml by FRETS). All patients initially improved when PEX was started, however, in 7/9 cases a drop in platelet count was noted on day 7 (n=5), 8 or 9 (each n=1), which was associated with a substantial increase in anti-ADAMTS13 antibody and functional inhibitor titer in all seven patients. CRP was increased (>30mg/L) in one patient only, during the three days before the raise in inhibitor titer and a drop in platelet count was noted, while total IgG remained stable in all 9 patients throughout PEX. At presentation none of the patients had a positive result for the thyroid antibodies, however, all 9 patients developed positive anti-TPO antibody titers during treatment and three patients tested positive for anti-TG antibodies at the same time. Anti-TPO antibody peaks occurred after the anti-ADAMTS13 antibody peak in all patients (range days 9–17), except the two patients where no raise in anti-ADAMTS13 antibody titers was observed (anti-TPO peak on day 3 in both). The two patients without inhibitor boosting required only five and six PEX sessions, respectively to get into remission, of the other seven patients two didn't overcome the inhibitor boosting and became refractory and were subsequently successfully treated by splenectomy or Rituximab, and one patient died of sepsis on day 11. Conclusions. Inhibitor boosting in acquired TTP due to antibody-mediated severe ADAMTS1313 deficiency treated with PEX is common (78%) and cannot be overcome by standard first line treatment in half of the patients. The fact that significant titers of other autoantibodies than anti-ADAMTS13 antibodies occur during the acute disease episode is striking and points to a more general dysregulation of the immune response in acquired TTP. Investigation of further autoantibodies, cytokines, etc. to explore the role of B-cells and T-cells in this phenomenon in more detail are underway. Disclosures: No relevant conflicts of interest to declare.

Eltrombopag and High-Dose Dexamethasone As First Line Treatment For ITP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3544-3544
Author(s):  
David Gomez-Almaguer ◽  
Miguel Angel Herrera-Rojas ◽  
Andres Gomez-de Leon ◽  
Olga Graciela Cantú-Rodríguez ◽  
Cesar H Gutiérrez-Aguirre ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Line Therapy ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that involves antibody and cell mediated destruction of platelets as well as suppression of their production. Prednisone is the initial standard therapy in adults1. High-dose dexamethasone as front-line therapy given as pulses of 40 mg per day for 4 consecutive days, was effective in 85% of patients, nevertheless, 50% relapsed within six months2. The prices of ITP drugs for 1 month of treatment in an adult range from prednisone; $16, eltrombopag; $5,934, intravenous immune globulin (IVIG) (80 g); $9,648, to rituximab (2 g); $15,5963. Only prednisone/dexamethasone and eltrombopag are available in oral presentation, for this reason, ambulatory treatment is an alternative for these patients. The trombopoietin receptor agonists are effective for the treatment of patients with chronic ITP, although response is dependent on continued administration. Eltrombopag is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of thrombopoietin. This drug effectively raises the platelet count in adult patients (aged 18 years and over) as second/third line therapy, that is for patients refractory to corticosteroids and IVIG who have had their spleen removed or when splenectomy is not an option4. Our group, as well as others, has previously sought to improve response rates in these patients, particularly with the use of rituximab5, 6. To our knowledge neither eltrombopag nor romiplostim have been used as front line therapy in ITP, therefore the purpose of this study was to assess the efficacy of eltrombopag and dexamethasone in this setting. Patients and Methods This was a prospective, phase 2 study, using the combination of eltrombopag (50 mg PO once a day for 4 weeks) and high-dose dexamethasone (40 mg PO days 1,2,3,4) in untreated adult patients with immune thrombocytopenia or in patients with less than 7 days of treatment with corticosteroids. Complete response (CR) was defined as an increase in platelet count >100×109/L. Partial response (PR) was defined as an increase in the platelet count greater to 30 ×109/L according to standard criteria. Duration of response was considered from the day of initial administration to the first time of relapse (platelet count <30×109/L). Results Twelve consecutive patients were enrolled from June 2012 to June 2013, 6 women and 6 men. The median age at diagnosis was 50 years (range, 20 - 80 years). The median platelet count at diagnosis was 7 x 109/L (range, 2 - 29 x 109/L). Patients were followed for a median of 2.5 months (range 1.1 - 13). After steroid treatment at day +5, ten patients had responded (83.3%), five had achieved CR (41.7%), and five PR. After completing treatment with eltrombopag at day +34, all patients responded (100%), nine patients achieved CR (75%) and three PR (25%). Two patients relapsed in a median time of 39.5 days (range, 30.1 - 49), both regaining CR after treatment with another high-dose dexamethasone course and low-dose rituximab (4 doses of 100 mg every week). At 3 months follow-up 66.7% remained in CR and 33.3% in PR (n=6). At 6 months follow-up two patients remained in CR and two in PR (n=4). Time to best response achieved was 34 days from diagnosis (range, 19 – 64.1). At the end of follow-up 9 patients (75%) remained in CR and 3 patients in PR (25%). Total treatment cost per patient was $1,640 approximately. Conclusion Currently the initial treatment of ITP patients is based on prednisone or high dose dexamethasone with or without IVIG. This approach is associated with high cost and high relapse rate. The results from our pilot study suggest that high dose dexamethasone and eltrombopag are very effective as first line treatment for acute ITP in adults. This treatment is ambulatory, affordable and well tolerated; however, we still don't know if this approach will have a favorable impact on the relapse rate of this disease. Disclosures: Off Label Use: Eltrombopag as first line treatment for ITP.

scholarly journals Romiplostim Treatment Pattern of Adult Chronic Immune Thrombocytopenia in Routine Clinical Care in Three Nordic Countries

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4998-4998
Author(s):  
Mette Nørgaard ◽  
Nickolaj Risbo Kristensen ◽  
Henrik Frederiksen ◽  
Shahram Bahmanyar ◽  
Waleed Ghanima ◽  
...  
Keyword(s):  
Platelet Count ◽  
Research Funding ◽  
Clinical Care ◽  
Previous Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Platelet Counts ◽  
Clinically Significant ◽  
First Line Treatment

Abstract Introduction Romiplostim was approved in 2009 in Europe for treatment of adult chronic immune thrombocytopenia (cITP) in splenectomized patients, refractory to other ITP treatments, and as second-line treatment for adult non-splenectomized patients. In 2016 the indication was extended to second-line treatment in all cITP patients. Few data exist on how romiplostim is used in routine clinical care. Methods To examine romiplostim treatment patterns we used the Nordic Country Patient Registry for romiplostim (NCPRR). NCPRR was established in 2009 and includes all adult (≥18 years) patients in Denmark, Sweden and Norway with a confirmed cITP (ITP lasting >6 months) diagnosis requiring hospital contact. The cohort is based on data from national health registries and enriched by medical record review. All patients diagnosed with cITP from April 1, 2009 to December 31, 2016 (data cut-off) are included. We describe age, comorbidity, previous treatment, platelet level, and both romiplostim dose and duration in patients who started romiplostim after date of their cITP diagnosis by line of treatment. Results Among 2895 patients diagnosed with cITP: 103 patients started romiplostim treatment before the data cut-off. Of these, 40% were aged 18- 50 years old, 30% were 35-70 years old, and 30% were ≥71 years. A total of 76% had no recorded comorbidity. Romiplostim was first-line treatment in 8 cITP patients of whom one had been splenectomized. In the month before romiplostim start, six of these patients (75%) had platelet count <50x109/L, but only one patient had experienced clinically significant bleeding (see Table). Twenty cITP patients started romiplostim as second-line treatment: duration of non-romiplostim first-line treatment had been <3 months in 50%, 3-12 months in 25%, and ≥12 months in 25%. Fourteen (70%) second-line romiplostim patients had obtained a platelet count of >150x109/L during their first-line treatment. In the month prior to romiplostim initiation, 3 (15%) patients experienced a bleeding event, while median latest platelet count was 10 x109/L (inter quartile range, IQR :10, 38). Romiplostim was third-line treatment in 44 patients: in the month prior to initiation, median latest platelet count was 15 x109/L (IQR: 10-32), and 20 (46%) patients experienced clinically significant bleeding events. Duration of non-romiplostim second-line treatment was ≤1 month in 33 patients (75%) and between 1-6 months in 20%. During their second-line treatment, 17 (39%) patients did not reach a platelet count of >50x109/L and 15 (34%) had a highest platelet count of 50 to 150x109/L. In the remaining 31 romiplostim-treated patients, it was used as fourth or later treatment line: median latest platelet count in the month preceding initiation was 14 x109/L (IQR: 5-27), with 7 (22.6%) patients experiencing clinically important bleeding during this time. Duration of the previous treatment in these patients had been ≤1 month in 16 (52%) and 1- 3 months in 12 (39%) patients. During their previous line of treatment 14 (45%) patients did not reach a platelet count of >50x109/L and an additional 9 (29%) had a highest platelet count of 50 to 150x109/L. In patients initiating romiplostim at first-line, median maximum platelet count while on therapy was 147x109/L (IQR: 109-237): this value was 299x109/L (IQR: 187,752), 295x109/L (IQR: 107,454), and 132x109/L (IQR: 52-305) for second, third, and fourth-or-later lines respectively. Median duration of romiplostim therapy was shortest at first-line (37 days, IQR: 21-180), and longest at second-line (91 days, IQR: 21, 169). Two patients on second-line, and 8 patients on third-line eltrombopag, switched to romiplostim. Conclusion Approximately 4% of cITP patients were treated with romiplostim, predominantly at third or later treatment lines: median platelet counts were seen to improve from <20 x109/L prior to romiplostim initiation to >100x109/L while on therapy across all lines. Romiplostim treatment had a relatively short duration. However, romiplostim-treated patients were characterized by a short duration on their previous non-romiplostim treatment line, and a high proportion had low platelet counts during this prior treatment. These data indicate that romiplostim is effective at increasing platelet counts in cITP patients with varying clinical history. Larger studies are needed to confirm these results and investigate drivers at different lines of therapy. Disclosures Bahmanyar: Amgen: Research Funding. Ghanima:GlaxoSmithKline and Pfizer: Other: Personal Fees; Roche, Amgen, Novartis, Bayer, BMS: Other: Personal Fees, Research Funding. Alam:Amgen: Employment, Equity Ownership. Christiansen:Amgen: Research Funding.

scholarly journals Tacrolimus Plus High-Dose Dexamethasone Versus High-Dose Dexamethasone Alone As First-Line Treatment for Adult Immune Thrombocytopenia: The Phase 2, Open Label, Randomized Trial (TARGET 020)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Zhuo-Yu An ◽  
Ye-Jun Wu ◽  
Yun He ◽  
Xiao-Lu Zhu ◽  
Hong-Xia Shi ◽  
...  
Keyword(s):  
Platelet Count ◽  
Combination Group ◽  
High Dose ◽  
Line Treatment ◽  
Monotherapy Group ◽  
First Line ◽  
Open Label ◽  
High Dose Dexamethasone ◽  
First Line Treatment

Abstract Introduction Immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease and one of the most common bleeding disorders seriously endangering human health. Glucocorticoids and intravenous immunoglobulin are first-line treatments recommended by guidelines for patients with ITP. However, approximately 50%-85% of patients relapse during the first year of treatment. In addition, long-term use of glucocorticoids increases the risk for dose- and time-dependent glucocorticoid-related complications and serious side effects. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP are urgently needed. Tacrolimus is a calcineurin inhibitor, which forms a complex by binding to FK506-binding protein. It is currently widely used in the prevention of graft-versus-host disease for organ transplantation as well as for the treatment of autoimmune diseases. In addition to recent retrospective studies and case reports demonstrating its effectiveness in ITP, tacrolimus has been shown to improve anti-platelet antibody-mediated thrombocytopenia in mice, suggesting it may be a potential treatment for ITP. The aim of this study was to compare two first-line treatment options for ITP-a standard glucocorticoid-only regimen versus tacrolimus in combination with a standard glucocorticoid regimen-to determine which could help patients achieve stable platelet counts faster and experience a longer duration of remission. Methods This open-label, randomized, phase 2 trial, enrolled adult ITP patients from seven different tertiary medical centers in China. Elderly patients had confirmed, newly diagnosed, treatment-naive ITP, platelet counts &lt;30×10 9/L, or &lt; 50×10 9/L and significant bleeding symptoms (World Health Organization bleeding scale ≥ 2). Eligible patients were randomly assigned 1:1 with an interactive web-based response system to receive either oral tacrolimus (initial 0.03 mg/kg/day and maintain blood concentration at 3-5 ng/mL for 12 weeks) plus high-dose dexamethasone (HD-DXM) or HD-DXM monotherapy for 12 weeks. DXM (40 mg) was administered orally daily for 4 consecutive days to both study arms. The 4-day course of DXM was repeated on days 11-14 in patients who lacked response by day 10. The primary endpoint was 6-month sustained response (SR), defined as platelet count maintained &gt;50×10 9/L without any additional ITP-modifying therapy at the 6-month follow-up. Key secondary endpoints included initial response by day 14 (OR, platelet count ≥30×10 9/L and at least 2-fold increase in baseline platelet count and absence of bleeding; and CR, platelet count ≥ 100×10 9/L), duration of response, bleeding scores, and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04747080). Results Total 140 patients newly diagnosed with ITP were randomly assigned to either the tacrolimus plus HD-DXM (n=72) or HD-DXM monotherapy (n=68) groups. At the 6-month follow-up, the proportion of patients exhibiting SR was significantly higher in the tacrolimus plus HD-DXM group than in the HD-DXM monotherapy group (65.3% vs 42.6%, p= 0.007). Of the 140 patients with ITP (males accounted for 48.6%), the mean age was 32.8 years, the mean platelet count was 16.7×10 9/L. The combination group exhibited a higher 14-day early remission rate than the monotherapy group (76.4% vs 55.9%, P=0.001). Significantly fewer treatment failures occurred in patients randomly assigned to the combination group(19.4% vs 38.2%, P=0.0014). During the follow-up period, fewer patients in the combination group experienced relapse than in the monotherapy group; the median time to relapse was 77 days (Tacrolimus+HD-DXM) vs 36 days (HD-DXM). The combination group exhibited a lower proportion of bleeding events and a lower bleeding score. The incidence of serious AEs, rescue therapy, and treatment side effects were similar between the two groups, and treatment was well tolerated by all patients, with no grade 4 AEs or treatment-related deaths reported. There was no statistically significant difference in the incidence of treatment-related AEs between the two groups. Conclusions Low-dose tacrolimus plus HD-DXM was an effective and safe treatment for ITP as first-line therapy and elicited a sustained prolonged response in adults. This therapy may be a new treatment option for adult patients with ITP. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: It includes information or discussion of off-label drug use of tacrilimus.

scholarly journals Effect of Helicobacter pylori infection on the first-line treatment outcomes in patients with immune thrombocytopenic purpura

2021 ◽  
Author(s):  
Ali Dogan ◽  
Omer Ekinci ◽  
Senar Ebinc
Keyword(s):  
Helicobacter Pylori ◽  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Eradication Therapy ◽  
Line Treatment ◽  
First Line ◽  
Thrombocytopenic Purpura ◽  
Significant Difference ◽  
H Pylori ◽  
First Line Treatment

Background: Helicobacter pylori (H. pylori) eradication therapy is known to increase the platelet count, but in immune thrombocytopenic purpura (ITP), the effect of H. pylori infection on the response to treatment is not clear. This study aims to determine whether the response to the first–line treatment is affected by the states of H. pylori–positivity and –negativity in ITP patients. Methods: Adult newly diagnosed or chronic ITP patients who had not received eradication therapy for H. pylori infection were included. Characteristics of the patients, presence and severity of bleeding, initial platelet count, administered treatments, and treatment response rates were inspected. Results: Of 119 total patients, 32 (26.9%) were H. pylori–positive, 87 (73.1%) were H. pylori–negative. The most common treatment was standard–dose steroid in both groups (62.5% vs 68.9%, p=0.524). Rates of complete response, partial response, no response were comparable for the two groups (respectively, 75% vs 73.6%, and 18.8% vs 19.5%, and 6.2% vs 6.9%), and there was no significant difference between the groups (p=0.283). Conclusion: It can be stated according to the present study that; in ITP patients in whom treatment is indicated, the response to the first–line treatment without the administration of H. pylori eradication therapy is comparable between H. pylori–positive and H. pylori–negative patients. Keywords: Helicobacter pylori, immune thrombocytopenic purpura, first-line treatment

scholarly journals Rituximab as first-line treatment for acquired thrombotic thrombocytopenic purpura

2017 ◽  
Vol 45 (3) ◽  
pp. 1253-1260 ◽  
Author(s):  
Haifei Chen ◽  
Ailin Fu ◽  
Jing Wang ◽  
Tianqin Wu ◽  
Zhengyang Li ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Plasma Volume ◽  
Peripheral Blood ◽  
Line Treatment ◽  
Adamts13 Activity ◽  
Total Plasma ◽  
First Line ◽  
Thrombocytopenic Purpura ◽  
First Line Treatment

Objective To investigate the efficacy and safety of rituximab (RTX) as first-line treatment of acquired thrombotic thrombocytopenic purpura (aTTP). Methods Twenty-five patients with acute aTTP and/or severe a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency were admitted to our centre from April 2009 to March 2015. Fourteen patients received RTX plus standard therapy (plasma exchange and corticosteroids) at acute episodes. Haemoglobin, platelet count, schistocytes, lactate dehydrogenase levels, ADAMTS13 activity and its inhibitors, and the ratio of B lymphocytes in the peripheral blood, were monitored. The number of plasma exchange (PEXs), total plasma volume, remission time, relapse ratio, and adverse effects were recorded. Results The median number of PEXs was 5 (2–17) sessions and median total plasma volume was 168.43 ml/kg (62.86–469.52 ml/kg). Patients achieved haematological remission at a median of 15 days (5–22 days), and the median time of immunological remission was 2 weeks (2–8 weeks) with a median follow-up of 13 months (3–61 months). ADAMTS13 activity significantly increased after 2 weeks. The B lymphocyte percentage in peripheral blood was reduced 1 week after the first dose of RTX infusion compared with before treatment (2.21% ± 5.23% vs 18.47% ± 7.34%, P = 0.000 [the result of statistical software]), and began to gradually increase 9 months later. Severe adverse effects and relapsing TTP were not observed during therapy and follow-up. However, one patient who had sustained immunological remission died of severe pneumonia 7 months later. Conclusion Although our study was limited by its small sample number and it was a non-controlled, clinical trial, it showed potential benefits of RTX therapy for acute aTTP. RTX may be administered as a first-line therapy for lowering patients’ relapse rate in the long term. Randomized, controlled trials of RTX for aTTP are required.

scholarly journals Lower lymphocyte percentage and higher platelet count as poor prognostic factors for patients with epidermal growth factor receptor–mutated lung adenocarcinoma receiving tyrosine kinase inhibitors as first-line treatment

2019 ◽  
Author(s):  
Yi-Feng Wu ◽  
Chih-Bin Lin ◽  
Sung-Chao Chu ◽  
Wei-Han Huang ◽  
Jen-Jyh Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Line Treatment ◽  
First Line ◽  
Epidermal Growth ◽  
First Line Treatment

Abstract Background This study evaluated the effect of clinical factors on the treatment outcomes of patients with lung adenocarcinoma with active epidermal growth factor receptor (EGFR) mutations who received tyrosine kinase inhibitors (TKIs) as first-line treatment. Methods Patients with stage IIIb or IV lung adenocarcinoma with mutated EGFR were enrolled retrospectively between March 2010 and December 2017. The effects of various clinical features and hematologic markers on progression-free survival (PFS) and overall survival (OS) were analyzed. Results A total of 190 patients were enrolled in this study. In univariate analysis, the male sex, smoking history, EGFR mutation with L858R, and presentation with malignant pleural effusion at initial diagnosis were significantly associated with shorter PFS or OS. Among hematologic markers, lower lymphocyte percentage and higher platelet count were associated with significantly poor PFS and OS. Stepwise multivariate Cox regression analysis showed that smoking history, EGFR mutation with L858R, and lower lymphocyte percentage were independent poor prognostic factors for PFS and OS. Presentation with malignant pleural effusion and higher platelet count was an independent poor prognostic factor for OS only. Conclusion Patients with lung adenocarcinoma receiving TKIs as the first-line treatment and having hematologic markers with lower lymphocyte percentage, and higher platelet count had poorer prognoses compared with other patients. Additional studies are warranted to elucidate the underlying mechanisms.

Hydroxychloroquine for the Treatment of Immune Thrombocytopenia Associated with Antinuclear Antibody in Patients Refractory to First-Line treatments .

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2414-2414
Author(s):  
Amélie Chabrol ◽  
Matthieu Mahévas ◽  
Nicolas Limal ◽  
Medhi Khellaf ◽  
Philippe Bierling ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Response Rate ◽  
Oral Prednisone ◽  
Line Treatment ◽  
Definite Diagnosis ◽  
Systemic Lupus ◽  
First Line ◽  
First Line Treatment

Abstract Abstract 2414 Poster Board II-391 Background and objective: Although, corticosteroids (CS) are commonly used as the first-line treatment for lupus-associated immune thrombocytopenia (ITP), few patients fail to respond to CS and a majority of the responders relapse when CS are withdrawn. Hydroxychloroquine (HCQ) is commonly used in both cutaneous and systemic lupus due to its immunomodulatory properties. In a previous report on lupus-associated immune thrombocytopenia (ITP), it has been suggested that HCQ could have an effect on the platelet count in this setting (Arnal C et al. J Rheumatol 2002). The objective of the study was to better assess the efficacy of HCQ as a treatment of ITP associated with positive antnuclear antibody (ANA) in patients who failed to achieve a durable response after a first-line treatment. Patients and Methods: This single centre retrospective study was conducted at the French national referral center for adult's immune cytopenias. To be included in the study, all patients had to fulfil the following criteria: 1) Definite diagnosis of ITP with a platelet count < 50 × 109/l at diagnosis 2) Positive ANA at a significant titer (i.e ≥ 1/160 on Hep2 cells), with or without a definite diagnosis of systemic lupus erythematosus (SLE) according to the ACR-revised criteria and 3) No response or incomplete response to at least one previous treatment-line. Response to HCQ was considered when the platelet count was persistently (at least for 3 consecutive months) maintained above 150×109/l (complete response: CR), and when the platelet count increased and persisted above 30 × 109/l with at least a doubling of the baseline count (partial response: PR). Results: The data from 40 patients (32 F, 8 M) with a median age of 35 yrs (range: 15-75) were analyzed. The median platelet count at ITP diagnosis was 13×109/l (range: 1-46). Twelve (30%) patients had a SLE-associated ITP (4 or more SLE ACR-criteria) whereas 28 patients (70%) had positive ANA without definite SLE. The median HCQ dose was 200 mg bid (200 to 600 mg/d) and the median time between ANA-associated-ITP diagnosis and HCQ first administration was 4 months (range: 1-120). HCQ was given after failure of a median of 2 treatment-lines [1 to 5 including oral prednisone (n=39), IVIg (n=15), danazol (n=5), dapsone (n=2), splenectomy (n=2), anti-D (n=1) and immunosuppressive agents (n=2)]. HCQ was given in combination with other treatments in 36 patients (90%) including oral prednisone (n=36) (median initial dose: 50 mg/day, range: 30 to 65 mg/day), dapsone (n=8), danazol (n=5). The median duration of HCQ treatment was 5 years (range: 0.4 to 12 yrs). The overall response rate for was 60% (24/40), with 18 CR and 6 PR. All the responses were sustained with a median follow-up of 64 months (range: 6 to 146 mths). At the end of the follow-up period, all concomitant therapies could be either stopped (n = 29 patients) or tapered [n = 7 patient left on low dose of prednisone (less than 10 mg/d)]. The response rate was significantly higher in the SLE group (83%; 10/12) when compared to the ANA-positive group (50%; 14/28) (p <0.05). The overall safety of HCQ was good and none of the patients stopped the treatment because of a side-effect. Blood HCQ concentration was checked in 2 non-responding patients and was found below therapeutic range in both cases. Conclusion: This retrospective study strongly suggests that HCQ is a safe, and effective treatment for ITP patients with high titer of ANA who failed to achieve a lasting response after a first-line treatment and mainly after CS. HCQ appears particularly attractive in the subgroup of patients who fulfil the SLE ACR-revised criteria. This costless treatment should therefore be systematically considered in this setting regardless SLE-activity. Moreover, it is likely that HCQ may also be helpful as a corticosteroid-sparing strategy in patients with chronic ITP and positive ANA but this observation needs further confirmation throughout a prospective analysis. Disclosures: No relevant conflicts of interest to declare.

Efficacy Of Helicobacter Pylori Eradication For The First Line Treatment Of Immune Thrombocytopenia Patients With Moderate Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2324-2324
Author(s):  
Hyo Jung Kim ◽  
Won Sik Lee ◽  
Hawk Kim ◽  
Jung-Hee Lee ◽  
Sang Min Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Base Line ◽  
Line Treatment ◽  
First Line ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Significant Difference ◽  
H Pylori ◽  
First Line Treatment

Abstract Background Since the first case report of Gimaz et al., several investigators have reported that the secondary immune thrombocytopenia (ITP) can occur in patients with Helicobactor pylori (H. pylori) infection. Eradication of H. pylori has been shown to result in improvement in thrombocytopenia. In one systematic review of 696 patients with H. pylori infection it showed 50.3% overall response (platelet count >= 30 X 109/L and at least a doubling of the base line count) after H. pylori eradication. Under these results, ASH 2011 guidelines for ITP recommended that eradication therapy be administered in adult patients who are found to have H. pylori infection (grade 1b). But also they recommended that treatment be administered for newly diagnosed patients with a platelet count < 30 X 109/L. To the best of our knowledge, there was no prospective study to evaluate the efficacy of H. pylori eradication for ITP patient with moderate thrombocytopenia and positive H. pylori. In Korea, the prevalence of H. pylori was reported as high as 60 – 65% in general adult population. The response rate and price of 1st line triple regimen for H. pylori eradication were known to be 70 - 80% and around 100 US dollars in Korea. With these circumstances, tolerable treatment like H. pylori eradication for ITP patients with platelet count >=30 X 109/L is challengeable. Thus, we performed the prospective multicenter phase II study to evaluate the efficacy of H. pylori eradication for the 1st line treatment of persistent or chronic ITP patients with moderate thrombocytopenia. Methods We enrolled patients with persistent (3 to 12 months from diagnosis) or chronic (lasting for more than 12 months) ITP defined by international working group. The platelet counts of patients were between 30 X 109/L and 70 X 109/L. And all patients had positive result of C13-urea breath test (UBT) and had never been treated for ITP or H. pylori. Patients with other secondary ITP could not be enrolled. Patients received lansoprazole 30mg twice daily, amoxicillin 1000mg twice daily and clarithromycin 500mg, twice daily for one week. Eradication of H. pylori was evaluated at eighth week after treatment by UBT. Platelet counts were monitored at 2 weeks and after then at every month for a year. Complete response (CR) was defined as a platelet count >= 100 X 109/L. Partial response (PR) was defined as a platelet increase of >= 30 X 109/L and at least a doubling of the base line count. The primary endpoint was CR rate at 3 months after treatment. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT01255332). Results Twenty-six patients were enrolled between November 2010 and May 2013 from 6 medical centers in Korea. Two patients with HCV infection and one patient with more than 70 X 109/L of platelet counts were excluded from analysis. The mean initial platelet counts of 23 patients (7 males, 16 females, median age 43 years and range 19 - 58 years) was 52.7 ± 9.5 X 109/L (range 39 – 68 X 109/L). All patients except one checked UBT after treatment and H. pylori eradication was achieved in 86.3% (19/22) of patients. CR was obtained in 13 of 23 patients (56.5%) within 3 months after treatment. And no PR was found until this time point. The median time to CR after initiating treatment was 4 weeks (range 2 – 8 weeks). CR rate of the patients who achieved H. pylori eradication was 63.2% (12/19). Unlike other reports, there was no significant difference on initial platelet counts among CR group and non-responder group and no significant correlation on the platelet levels between baseline and initial 3 months (Fig 1). Only 2 of 26 patients could not continue medication due to nausea and diarrhea, respectively. There was no other significant adverse event. Conclusion The eradication of H. pylori is an effective first line treatment for persistent or chronic ITP with moderate thrombocytopenia with high CR rate and rapid onset. And it has acceptable toxicity and relatively low cost. This study supports routine detection and eradication of H. pylori infection in ITP patients especially in populations with a high prevalence of this infection. Disclosures: No relevant conflicts of interest to declare.

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