Recombinant Human Thrombopoietin and Rituximab vs Rituximab Monotherapy in Corticosteroid-Resistant Primary Immune Thrombocytopenia: a Multicenter Randomized Controlled Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 329-329
Author(s):  
Miao Xu ◽  
Ping Qin ◽  
Xiaoyuan Dong ◽  
Jie Li ◽  
Haiyan Zhang ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Wilcoxon Test ◽  
Fixed Dose ◽  
Combination Group ◽  
Monotherapy Group ◽  
Platelet Counts ◽  
Primary Immune Thrombocytopenia ◽  
Time To Relapse

Abstract Background Though great progresses had been achieved in the management of primary immune thrombocytopenia (ITP), still 25%-30% of the patients show no response to the conventional therapy. Both thrombopoietin (TPO) and rituximab (RTX) are recommended as the second-line treatments. TPO has shown potent activity in ITP, but the therapeutic efficacy is dependent on continual administration. Rituximab is an anti-CD20 chimeric monoclonal antibody which could induce prolonged remission in ITP. However, longer time to response was also reported. The combination of rhTPO and rituximab could complement each other in both mechanism of action and time window, exert powerful effect, which may be a choice for the glucocorticosteroids-resistant/relapsed patients. Method Patients with platelet counts ≤ 30 x109/L, or ≤ 50 x109/L with bleeding symptoms from 12 centers were enrolled in the study. Subjects enrolled in the study were assigned randomly as 1: 2 to RTX group and rhTPO plus RTX group. Eligibility criteria were set according to the recently published guideline (Rodeghiero F, et al, Blood 2009). Approval for the study was obtained from the Ethics Committee of the School of Medicine and Qilu Hospital. Informed consent in accordance with the Declaration of Helsinki was given to each patient. Rituximab (MabThera; Roche) was given with a fixed dose of 100mg weekly for four weeks. And in the combination group, rhTPO (Tebiao, 3SBio, China) was added in the regimen with a dose of 300U/kg/day in the first 14 days, and a modified frequency of rhTPO was given according to the platelet counts after two weeks, but no longer than four weeks. Primary outcomes include response (R), complete response (CR), no response (NR) and relapse. All the criteria were consent with the definition and outcome criteria. (Rodeghiero F, et al. Blood, 2009.) Secondary outcomes are listed below. Time to response (TTR) was considered as the duration from baseline to response. Time to relapse was also measured with Kaplan-Meier analysis. Besides, safety was reflected as adverse events graded according to the Common Toxicity Criteria. This clinical trial was registered at http://clinicaltrials.gov as NCT 01525836. Result A total of 114 patients were recruited: monotherapy group (n = 35) and combination group (n = 79). All patients failed to response to glucocorticosteroids or relapsed after corticosteroids treatment. Response rate was reached in 71.4% (25/35) of patients in monotherapy group vs. 78.5% (62/79) in the RTX and rhTPO combination group, while complete responses were achieved as 10/35 (28.6%) in RTX monotherapy group and 34/79 (43.0%) in rhTPO plus RTX group respectively. Median time to response was 28 days (range 4-90 days) in RTX group, while in RhTPO plus RTX group, TTR was 7 days (range 4-28 days) (P = 0.002). There was significantly longer time to relapse in the combination group (shown in Fig. 1). Adverse effects were observed in RTX group in 5 patients, most of whom were affected with inflammation. One patient was reported as viral myocarditis, and there were also complaints about chill, rash and hyperpyrexia. And incidence of adverse events was slightly increased in rhTPO plus RTX group. There were 14 adverse effects reported in the combination group, such as fatigue, pulmonary inflammatory, but all were below Grade 2. Conclusion Our findings suggest that combination of RTX and RTX in ITP yields shorter time to response compared with monotherapy of RTX, and moreover, combination extended time to relapse. Thus, combination therapy may represent an effective treatment option for glucocorticosteroids-resistant or relapsed patients. The results were compared with Gehan-Breslow-Wilcoxon Test. (P = 0.0140) Disclosures: No relevant conflicts of interest to declare.

Deviation from Guidelines in Use of Eltrombopag and Romiplostim in Clinical Practice for Children with Primary Immune Thrombocytopenia; Multi-Center Egyptian Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4907-4907
Author(s):  
Mohsen Saleh Elalfy ◽  
Tamer Hassan ◽  
Khalid Elsayh ◽  
Mohamed Maebid ◽  
Hoda Hassab ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Escalation ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Severe Bleeding ◽  
Inadequate Response ◽  
Serious Adverse Events ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Primary Immune Thrombocytopenia

Background: Primary immune thrombocytopenia (ITP) has been treated with steroids or immune-suppressive. Thrombopoietin receptor agonists (TPO-RAs), changed the treatment landscape for ITP. Romiplostim and Eltrombopag were FDA approved for use in pediatric patients ≥1 year with ITP of >6 months' duration and insufficient response to previous therapy. Following the guidelines is not always feasible in practice. Aim and Methodology Centers treating more than 25 new cases/year with good recording system were included; aiming to report outcome, adverse events (AEs) and deviation from guidelines. Newly diagnosed ITP children were excluded. Data was collected from January 2017- June 2019; children age >1 to 18 years with persistent ITP (3-<12 months) or chronic (≥12 months), who had previously been treated with ≥1 previous ITP therapy, and had platelet counts (PC) persistently <30×109/l with moderate-severe bleeding. Eltrombopag was described in a dose of 25 mg/day for those > 1 to 12 years; or in 50 mg/day for those >12-18 years; dose was escalated to 50 or 75mg/day for those 6-12 and >12 years respectively on failure to have PC > 50 x 109/L. Weekly CBC and self-record of bleeding for 1st 24 week then bi-weekly. Failure to show a good response; Eltrombopag dosing should be adjusted to achieve that goal and not to exceed 200 × 109/L. Romiplostim was used in 1 ug/kg and escalated up to 10 ug/kg according to response. Serious AEs were reported to ethical committee within 24 hours. Results Two years Observational study of 204 out of 1080 primary ITP (268 persistent and 812 chronic); 55% females median age 8 years, received Eltrombopag (n=186), Romiplostim (n= 18) from 3-30 months was prescribed after failure of 1-5 lines of therapy in 15% of Persistent ITP and 20% of chronic ITP. Adequate response at 24 weeks in 60% on Eltrombopag or Romiplostim had a significant reduction in both skin-related and non-skin-related bleeding symptoms). However 50% discontinued treatment; (40% due to inadequate response, 8% irregular availability and 2% due to SAEs). Deviation from guidelines in 40%; (15% started Eltrombopag early between 3-6 months who showed a higher response rate; half of them could stop it without drop of PC); while 20% continued Eltrombopag for >12 month with lack of response after dose escalation at 24th week and 5% were not following the described dose or the regular monitoring. 40% of chronic ITP patients achieved platelet counts of >50 x 109/L or more at least twice. Common adverse events included; headache (10%). myalgia (10%), rhinitis (8%), diarrhea 8% Serious adverse events occurred in 4 (1 elevated transaminases, one unrelated life-threatening bleeding and two high PC; >1000 x109/L). Conclusion: TPO-RAs were used in almost 15% of persistent and 20% of chronic ITP as 2nd line or more therapy and in 90% was Eltrombopag; which produced an excellent response for those 3-6 months; deviating from guidelines. It showed a sustained platelet response in 40% of patients with chronic ITP, however it should be stopped if showing poor response after dose escalation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Sustained Remission in Patients with Primary Immune Thrombocytopenia after Romiplostim Tapering and Discontinuation: A Case Series in Real Life Management in Spain

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
María-Eva Mingot-Castellano ◽  
Carlos Grande-García ◽  
David Valcárcel-Ferreiras ◽  
Clara Conill-Cortés ◽  
Loreto de Olivar-Oliver
Keyword(s):  
Clinical Practice ◽  
Predictive Factors ◽  
Immune Thrombocytopenia ◽  
Real Life ◽  
Case Series ◽  
Sustained Remission ◽  
Platelet Counts ◽  
Thrombopoietin Receptor ◽  
Primary Immune Thrombocytopenia ◽  
Effective Option

Romiplostim, a thrombopoietin-receptor agonist (TPO-ra), is a highly effective option in primary immune thrombocytopenia (ITP), with 80–90% of patients achieving platelet responses after few weeks of treatment. The evidence showing remissions, that is, sustained platelet counts after romiplostim discontinuation, in patients with ITP refractory to immunosuppressive therapy is steadily increasing. However, there is a lack of guidelines or recommendations addressing how and when to taper romiplostim in clinical practice in patients maintaining elevated and stable platelet counts. Furthermore, given the high heterogeneity of ITP patients, no associated predictive factors have been currently identified. Here, we present 4 representative clinical cases of the daily clinical practice in Spain comprising newly diagnosed, persistent, and both splenectomized and nonsplenectomized chronic ITP patients treated with romiplostim, achieving and maintaining clinical remission (platelet count ≥ 50×109/L for 24 consecutive weeks in the absence of any treatment for ITP) after treatment tapering and discontinuation, without observed safety concerns. Prospective studies identifying clinical and biological predictive factors of sustained response are warranted.

scholarly journals Eltrombopag for use in children with immune thrombocytopenia

2018 ◽  
Vol 2 (4) ◽  
pp. 454-461 ◽  
Author(s):  
Taylor Olmsted Kim ◽  
Jenny Despotovic ◽  
Michele P. Lambert
Keyword(s):  
Adverse Effects ◽  
Immune Thrombocytopenia ◽  
Safety Data ◽  
The Body ◽  
Double Blind ◽  
Platelet Counts ◽  
Blood Disorder ◽  
Thrombopoietin Receptor ◽  
Clinically Significant ◽  
Chronic Immune Thrombocytopenia

Abstract Eltrombopag is currently the only US Food and Drug Administration–approved thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia (ITP) in children. This oral, once-per-day therapy has shown favorable efficacy and adverse effect profiles in children. Two multicenter, double-blind, placebo controlled clinical trials (PETIT [Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)] and PETIT2 [Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body]) demonstrated efficacy in raising platelet counts, reducing bleeding, and reducing the need for concomitant ITP therapies with relatively few adverse effects. The most commonly reported drug-related adverse effects include headache, nausea, and hepatobiliary laboratory abnormalities. Long-term safety data in children are limited, and studies in adults have not revealed a clinically significant increased incidence of thrombosis, marrow fibrosis, or cataract formation. Eltrombopag has also been approved for treating refractory severe aplastic anemia (AA) and has potential for expanded use in ITP and severe AA as well as in other conditions associated with thrombocytopenia.

Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia

Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2755-2762 ◽  
Author(s):  
Francesco Zaja ◽  
Michele Baccarani ◽  
Patrizio Mazza ◽  
Monica Bocchia ◽  
Luigi Gugliotta ◽  
...  
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Salvage Therapy ◽  
Immune Thrombocytopenia ◽  
Sustained Response ◽  
Effective Treatment Option ◽  
Serious Adverse Events ◽  
Primary Immune Thrombocytopenia ◽  
Grade 3 ◽  
To Receive

Abstract Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 × 109/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m2 rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count ≥ 50 × 109/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, −0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, −0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.

Romiplostim Treatment in Adults with Immune Thrombocytopenia of Varying Duration and Severity

2015 ◽  
Vol 134 (4) ◽  
pp. 215-228 ◽  
Author(s):  
Ann Janssens ◽  
Michael Tarantino ◽  
Robert J. Bird ◽  
Maria Gabriella Mazzucconi ◽  
Ralph V. Boccia ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Type I Collagen ◽  
Type I ◽  
Serious Adverse Events ◽  
True Incidence ◽  
Platelet Counts ◽  
New Class ◽  
Third Line ◽  
Uncontrolled Bleeding

Romiplostim is recommended for the second- and third-line treatment of primary immune thrombocytopenia (ITP). We conducted a large, single-arm study (clinicaltrials.gov; NCT00508820) with broad entry criteria to evaluate the safety of romiplostim in adult ITP. Patients (n = 407) with ITP lasting 0.03-57.14 years and low platelet counts (median 14.0 × 109/l) or uncontrolled bleeding received romiplostim for up to 4 years. The rates of treatment-related, serious adverse events, serious hemorrhage events, thromboembolic events and fatal events were similar to those reported in previous romiplostim trials (0.2, 0.4, 0.2 and 0.1/100 patient-weeks, respectively). Bone marrow reticulin was observed in 4 patients, but biopsies were not routinely performed so the true incidence of this event cannot be determined. Type I collagen (nonserious, unrelated) was reported in 1 patient who likely had myelodysplastic syndrome. No new class of adverse events was reported. Platelet responses were achieved by >90% of the patients, typically within 1-2 weeks of the initiation of romiplostim treatment. From week 8, median platelet counts were >100 × 109/l; 47% of the patients received rescue medications (the use decreased over time). This study confirms and extends the tolerability/efficacy findings of previous romiplostim clinical studies. It was performed on a large ITP population, which is likely more representative of clinical practice.

A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 28-36 ◽  
Author(s):  
James B. Bussel ◽  
George R. Buchanan ◽  
Diane J. Nugent ◽  
David J. Gnarra ◽  
Lisa R. Bomgaars ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Double Blind Study ◽  
Weekly Dose ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Subcutaneous Injections ◽  
Platelet Counts ◽  
Short Term Study ◽  
Thrombopoietin Mimetic

Abstract Romiplostim, a thrombopoietin-mimetic peptibody, increases and maintains platelet counts in adults with immune thrombocytopenia (ITP). In this first study of a thrombopoietic agent in children, patients with ITP of ≥ 6 months' duration were stratified by age 1:2:2 (12 months-< 3 years; 3-< 12 years; 12-< 18 years). Children received subcutaneous injections of romiplostim (n = 17) or placebo (n = 5) weekly for 12 weeks, with dose adjustments to maintain platelet counts between 50 × 109/L and 250 × 109/L. A platelet count ≥ 50 × 109/L for 2 consecutive weeks was achieved by 15/17 (88%) patients in the romiplostim group and no patients in the placebo group (P = .0008). Platelet counts ≥ 50 × 109/L were maintained for a median of 7 (range, 0-11) weeks in romiplostim patients and 0 (0-0) weeks in placebo patients (P = .0019). The median weekly dose of romiplostim at 12 weeks was 5 μg/kg. Fourteen responders received romiplostim for 4 additional weeks for assessment of pharmacokinetics. No patients discontinued the study. There were no treatment-related, serious adverse events. The most commonly reported adverse events in children, as in adults, were headache and epistaxis. In this short-term study, romiplostim increased platelet counts in 88% of children with ITP and was well-tolerated and apparently safe. The trial was registered with http://www.clinicaltrials.gov as NCT00515203.

Combination of Recombinant Factor VIIa and Fibrinogen Corrects Clot Formation in Primary Immune Thrombocytopenia At Very Low Platelet Counts

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4667-4667
Author(s):  
Ole Halfdan Larsen ◽  
Jesper Stentoft ◽  
Deepti Radia ◽  
J∅rgen Ingerslev ◽  
Benny S∅rensen
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Primary Immune Thrombocytopenia

Abstract Abstract 4667 Introduction: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count and an increased risk of bleeding. Hemostatic treatment modalities, bypassing the need for platelet transfusion, would be desirable for control of serious acute bleeds in patients with ITP. This study aimed at (i) performing a thorough characterization of the coagulopathy of ITP, (ii) investigate new ways to obtain acute correction of the coagulopathy performing in vitro experiments with recombinant factor VIIa (rFVIIa, NovoSeven®), fibrinogen (RiaSTAP®), and the combination of rFVIIa and fibrinogen, and finally (iii) investigate the correlation of the hemostatic response to the baseline platelet counts of the ITP patients. We challenged the hypothesis that rFVIIa combined with fibrinogen concentrate can correct whole blood (WB) clot formation in patients suffering from ITP even at very low platelet counts. Methods: Blood from 12 ITP patients and 15 healthy controls was drawn into 3.2% citrate containing corn trypsin inhibitor 18.3μg mL−1 to inhibit artificial contact activation. The WB (mean platelet count 22 × 109L−1 (range 0–42)) was spiked in vitro with buffer (control), fresh donor platelets (+40×109 L−1), rFVIIa (1 or 4μg mL−1), or fibrinogen (1 or 3mg mL−1) as well as the combination of rFVIIa and fibrinogen. Dynamic WB coagulation profiles were recorded by ROTEM® Thromboelastometry using activation with tissue factor (0.03pM) and re-calcification. Parameters of clot initiation (clotting time, CT), clot propagation (maximum velocity, MaxVel) as well as clot termination (maximum clot firmness, MCF) were evaluated. Thrombin generation in “platelet-rich” ITP plasma was evaluated using calibrated automated thrombography. Overall differences between groups were evaluated by paired and unpaired t-tests as appropriate. Simple linear regression analyses were performed using the differences observed after addition of the various interventions (intervention – baseline) as the dependent variable (y) and the platelet count as the independent variable (x). The slope was used to evaluate dependency of the hemostatic response on the platelet count, whereas the intercept was used to evaluate the hemostatic response at very low platelet counts. A p-value less than 0.05 was considered statistically significant. Results: Compared with healthy controls the WB coagulation profiles of the ITP patients were characterized by a prolonged CT (mean: 1490 vs. 941s, p<0.001) as well as a markedly reduced MaxVel (3.4 vs. 9.7mm×100s−1, p<0.001) and MCF (38.2 vs. 49.4mm, p=0.01). Fibrinogen showed no positive hemostatic effect. Recombinant FVIIa reduced the CT (744s, p<0.001) and increased the MaxVel (6.28mm×100s−1, p<0.001) whereas no change was observed in the MCF. Thrombin generation in “platelet-rich” plasma supported the findings in WB. The improvement in CT following addition of rFVIIa was independent of the platelet count (p-values > 0.45) and the intercept showed a significant improvement at very low platelet counts (1μg mL−1: −643s, p<0.001; 4μg mL−1: −811s, p<0.001). In contrast, the increase in MaxVel after addition of rFVIIa was highly dependent on the platelet count (1μg mL−1: R2 = 0.81, p < 0.001; 4μg mL−1: R2 = 0.86, p < 0.001) and the intercept was not significant (1μg mL−1: 0.05mm×100s−1 p=0.87; 4μg mL−1: 0.54 mm×100s−1 p=0.15). The combination of fibrinogen and rFVIIa revealed a synergistic effect also showing an increased MCF (50.7mm) in addition to a reduced CT (794s) and improved MaxVel (7.9 mm×100s−1) displaying larger effects than following fresh donor platelet substitution (CT 1164s; MaxVel 6.96mm×100s−1; MCF 49.6mm). Furthermore, rFVIIa together with fibrinogen also showed a significant response at very low platelet counts in all parameters (Intercept: CT −788s, MaxVel 3.3mm×100s−1, MCF 13.9mm, p-values<0.004) Conclusions: Data suggest that rFVIIa combined with fibrinogen can correct the coagulopathy of ITP even at very low platelet counts, and may be an alternative to platelet transfusion. Clinical trials are needed to further investigate if this new treatment modality holds the potential to serve as an effective acute treatment option in ITP. Disclosures: Off Label Use: Recombinant activated factor VII (NovoSeven) and fibrinogen concentrate (RiaSTAP). In vitro data suggesting a haemostatic effect in primary immune thrombocytopenia will be presented. S∅rensen:Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; SOBI: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pentapharm: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Grifols: Research Funding; LFB: Research Funding; Octapharma: Research Funding.

scholarly journals IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP

2020 ◽  
Vol 4 (7) ◽  
pp. 1492-1500
Author(s):  
Manuel Carcao ◽  
Mariana Silva ◽  
Michele David ◽  
Robert J. Klaassen ◽  
MacGregor Steele ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Controlled Study ◽  
Severe Bleeding ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Platelet Counts ◽  
Life Threatening ◽  
Blinded Trial

Abstract Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs &lt;20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.

Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn’s Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

2019 ◽  
Vol 13 (9) ◽  
pp. 1097-1104 ◽  
Author(s):  
Tadakazu Hisamatsu ◽  
Takayuki Matsumoto ◽  
Kenji Watanabe ◽  
Hiroshi Nakase ◽  
Satoshi Motoya ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Multivariable Analysis ◽  
Dropout Rate ◽  
Rank Test ◽  
Combination Group ◽  
Monotherapy Group ◽  
Significant Difference

Abstract Background Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn’s disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher’s exact test, p <0.001]. Kaplan–Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

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