Response loss and development of neutralizing antibodies during long-term treatment with romiplostim in patients with immune thrombocytopenia: a case series

Background: Patients with immune thrombocytopenia (ITP) are at risk of bleeding and, paradoxically, thromboembolic events (TEEs), irrespective of thrombocytopenia. The risk of thrombosis is increased by advanced age, obesity, and prothrombotic comorbidities: cancer, hyperlipidemia, diabetes, hypertension, coronary artery disease, and chronic kidney disease, among others. Certain ITP treatments further increase the risk of TEE, especially splenectomy and thrombopoietin receptor agonists. Spleen tyrosine kinase (SYK) is a key signaling molecule common to thromboembolic and hemostatic (in addition to inflammatory) pathways. Fostamatinib is an orally administered SYK inhibitor approved in the USA and Europe for treatment of chronic ITP in adults. Methods: The phase III and extension studies included heavily pretreated patients with long-standing ITP, many of whom had risk factors for thrombosis prior to initiating fostamatinib. This report describes long-term safety and efficacy of fostamatinib in 146 patients with up to 5 years of treatment, a total of 229 patient-years, and assesses the incidence of thromboembolic events (by standardized MedDRA query). Results: Platelet counts ⩾50,000/µL were achieved in 54% of patients and the safety profile was as described in the phase III clinical studies with no new toxicities observed over the 5 years of follow-up. The only TEE occurred in one patient (0.7%, or 0.44/100 patient-years), who experienced a mild transient ischemic attack. This is a much lower rate than might be expected in ITP patients. Conclusion: This report demonstrates durable efficacy and a very low incidence of TEE in patients receiving long-term treatment of ITP with the SYK inhibitor fostamatinib. identifiers: NCT02076399, NCT02076412, and NCT02077192.

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The health economic implications of treatment with quetiapine: an audit of long-term treatment for patients with chronic schizophrenia

European Psychiatry ◽

10.1016/s0924-9338(01)00583-1 ◽

2001 ◽

Vol 16 (5) ◽

pp. 307-312 ◽

Cited By ~ 10

Author(s):

J. Lynch ◽

J. Morrison ◽

N. Graves ◽

D. Meddis ◽

M.F. Drummond ◽

...

Keyword(s):

Health Economic ◽

Case Series ◽

Chronic Schizophrenia ◽

Term Treatment ◽

Revolving Door ◽

Psychotic Symptoms ◽

Open Label ◽

Economic Implications ◽

Long Term Treatment

SummaryThis retrospective, case series audit assessed the clinical and health-economic impact of long-term treatment with quetiapine (‘Seroquel’), a new atypical antipsychotic, in patients with chronic schizophrenia.The study design was of a case series format, comprising patients entered from one centre into the open-label extension of a multicentre 6-week efficacy study. Twenty-one patients (15 male, six female; mean age 39 years) were studied, of whom 17 (81%) had been rated as ‘partially responsive’ to previous antipsychotics. Data on hospitalisations and information on symptoms were collected retrospectively for the 12 months before quetiapine treatment was initiated and for the 12 months after.Quetiapine was effective in reducing psychotic symptoms with mean BPRS scores reducing significantly, from 38 to 21 (P < 0.005). Motor function was also significantly improved with mean Simpson scale scores reducing from 15 to 12 (P < 0.005). Average inpatient days were reduced by 11% in year two (97 compared with 109 days) while the overall costs of treatment, including drug costs, fell by 5% (I£20,843 to I£19,827).Four patients had been hospitalised for longer than 5 years before starting quetiapine; these chronically institutionalised patients remained in hospital, despite improved clinical outcomes (mean BPRS scores after treatment of 34, compared with 43 before), for the full 12 months of quetiapine treatment. Were the data from this audit to be re-analysed excluding these four patients then average inpatient days would have been reduced by 33% (45 to 30 days) and overall cost of treatment by 19% (I£8617 to I£7011).This audit suggests that treatment with quetiapine over this 1-year period was associated with both clinical improvements and a decreased usage of inpatient services. The reduction in hospitalisation costs would appear to compensate for the increased cost of drug treatment. Significantly, potential savings appear to be greatest for those patients with a ‘revolving door’ pattern of repeated readmission.

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Safety of long-term treatment with cyclosporin A in resistant chronic plaque psoriasis: a retrospective case series

Journal of the European Academy of Dermatology and Venereology ◽

10.1111/j.1468-3083.2004.00877.x ◽

2004 ◽

Vol 18 (2) ◽

pp. 169-172 ◽

Cited By ~ 11

Author(s):

M Garcia-Bustinduy ◽

M Escoda ◽

FJ Guimera ◽

M Saez ◽

S Dorta ◽

...

Keyword(s):

Cyclosporin A ◽

Plaque Psoriasis ◽

Case Series ◽

Term Treatment ◽

Chronic Plaque Psoriasis ◽

Retrospective Case ◽

Retrospective Case Series ◽

Long Term Treatment

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Long-Term Management of Generalized Pustular Psoriasis with Infliximab: Case Series

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2008.07036 ◽

2008 ◽

Vol 12 (4) ◽

pp. 184-188 ◽

Cited By ~ 7

Author(s):

Shannon B. Routhouska ◽

Pranav B. Sheth ◽

Neil J. Korman

Keyword(s):

Case Reports ◽

Case Series ◽

Term Treatment ◽

Pustular Psoriasis ◽

Short Term Treatment ◽

Long Term Treatment ◽

Generalized Pustular Psoriasis ◽

Factor Α ◽

Term Management

Background: Infliximab, a tumor necrosis factor α antagonist, has recently been shown to be successful for the short-term treatment of generalized pustular psoriasis (GPP) in multiple case reports. Objective: The goal of this case series was to assess the efficacy of the longer-term management of GPP with infliximab. Methods: Three patients with severe GPP were followed to assess the efficacy of long-term treatment with infliximab. Results: Infliximab therapy was more efficacious with infusion every 6 to 8 weeks in combination with methotrexate. Conclusion: Infliximab may be efficacious for some patients for the long-term management of GPP. Maintaining a strict infliximab infusion schedule and concomitant methotrexate therapy may decrease infusion reactions and increase efficacy.

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Long-term treatment with romiplostim and treatment-free platelet responses in children with chronic immune thrombocytopenia

Haematologica ◽

10.3324/haematol.2018.202283 ◽

2019 ◽

Vol 104 (11) ◽

pp. 2283-2291 ◽

Cited By ~ 6

Author(s):

Michael D. Tarantino ◽

James B. Bussel ◽

Victor S. Blanchette ◽

Donald Beam ◽

John Roy ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Term Treatment ◽

Long Term Treatment ◽

Chronic Immune Thrombocytopenia

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Arthroscopic treatment of fragmented coronoid process with severe elbow incongruity

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.3415/vcot-11-06-0087 ◽

2013 ◽

Vol 26 (01) ◽

pp. 27-33 ◽

Cited By ~ 7

Author(s):

E. de Bakker ◽

D. Van Vynckt ◽

E. Coppieters ◽

H. van Bree ◽

B. Van Ryssen ◽

...

Keyword(s):

Clinical Signs ◽

Case Series ◽

Term Treatment ◽

Coronoid Process ◽

Heavy Exercise ◽

Term Outcome ◽

Long Term Outcome ◽

Long Term Treatment

SummaryThe purpose of this study was to investigate the long-term treatment results of fragmented coronoid process (FCP) in joints with a radio-ulnar step greater than 3 mm. Treatment of these patients only consisted of fragment removal, without correction of the incongruity.The eight Bernese Mountain Dogs (11 joints) included in this study showed obvious clinical signs of elbow disease and were diagnosed with severe elbow incongruity and concomitant FCP in the time period from 1999–2003. At that time, elbow radiography, computed tomography, and arthroscopy were performed. The mean follow-up period was 5.6 years. The follow-up consisted of a telephone questionnaire combined with a clinical and radiographic re-evaluation at our clinic.The questionnaire revealed that all dogs were either free of lameness or only lame following heavy exercise. One dog sporadically required medication after heavy exercise. The owner satisfaction rate was 100%. The clinical re-evaluation did not reveal any signs of pain or lameness in all cases. Range-of- motion was decreased in nine of the 11 elbows. Radiographs revealed an increase in severity of osteoarthritis in every case.In this case series, arthroscopic fragment removal without treatment of incongruity was demonstrated to be a valuable treatment option and may provide a satisfactory long-term outcome.

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Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study

Blood ◽

10.1182/blood-2012-04-425512 ◽

2013 ◽

Vol 121 (3) ◽

pp. 537-545 ◽

Cited By ~ 181

Author(s):

Mansoor N. Saleh ◽

James B. Bussel ◽

Gregory Cheng ◽

Oliver Meyer ◽

Christine K. Bailey ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Term Treatment ◽

World Health ◽

Concomitant Treatment ◽

Open Label ◽

Safety And Efficacy ◽

Platelet Counts ◽

Long Term Treatment ◽

Chronic Immune Thrombocytopenia

Abstract Patients with chronic immune thrombocytopenia may have bleeding resulting from low platelet counts. Eltrombopag increases and maintains hemostatic platelet counts; however, to date, outcome has been reported only for treatment lasting ≤ 6 months. This interim analysis of the ongoing open-label EXTEND (Eltrombopag eXTENded Dosing) study evaluates the safety and efficacy of eltrombopag in 299 patients treated up to 3 years. Splenectomized and nonsplenectomized patients achieved platelets ≥ 50 000/μL at least once (80% and 88%, respectively). Platelets ≥ 50 000/μL and 2 × baseline were maintained for a median of 73 of 104 and 109 of 156 cumulative study weeks, respectively. Bleeding symptoms (World Health Organization Grades 1-4) decreased from 56% of patients at baseline to 20% at 2 years and 11% at 3 years. One hundred (33%) patients were receiving concomitant treatments at study entry, 69 of whom attempted to reduce them; 65% (45 of 69) had a sustained reduction or permanently stopped ≥ 1 concomitant treatment. Thirty-eight patients (13%) experienced ≥ 1 adverse events leading to study withdrawal, including patients meeting protocol-defined withdrawal criteria (11 [4%] thromboembolic events, 5 [2%] exceeding liver enzyme thresholds). No new or increased incidence of safety issues was identified. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts in the desired range. This study is registered at www.clinicaltrials.gov as NCT00351468.

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