Indeed, health\related quality of life for patients with ITP may be worse than that of patients with many other chronic conditions, including hypertension and arthritis.2 First\line treatments for ITP include corticosteroids (prednisone, dexamethasone), intravenous immunoglobulin (IVIg), and anti\D (Rh0) immunoglobulin.3 These therapies are used as upfront treatment in newly diagnosed patients and also as rescue therapies in patients with established ITP, with the goal of rapidly elevating platelet counts and preventing or controlling bleeding events.4 While corticosteroids and immunoglobulins produce an initial response in most patients (60%\70% and 90%, respectively), the response is usually transient ( 6 months and 2C4 weeks, respectively) and the medications must be readministered if the patient’s platelet count does not stabilize.5 Repeated or prolonged administration of first\line therapies is typically not suitable due to significant adverse effects (eg, osteoporosis, diabetes, cataracts, weight gain, infections) with corticosteroids and high cost, inconvenience of frequent infusions, and debilitating post\infusion headache with immunoglobulins.4, 6, 7 Spontaneous remissions in patients who have never received treatment are uncommon in adults with ITP (9%). patients.1 The disease may have a substantial impact on the patient’s quality of life, resulting, at least in part, from significant treatment burden. Indeed, health\related quality of life for patients with ITP may be worse Demethoxydeacetoxypseudolaric acid B analog than that of patients with many other chronic conditions, including hypertension and arthritis.2 First\line treatments for ITP include corticosteroids (prednisone, dexamethasone), intravenous immunoglobulin (IVIg), and anti\D (Rh0) immunoglobulin.3 These therapies are used as upfront treatment in newly diagnosed patients and also as rescue therapies in patients with established ITP, with the goal of rapidly elevating platelet counts and preventing or controlling bleeding events.4 While corticosteroids and immunoglobulins produce an initial response in most patients (60%\70% and 90%, respectively), the response is usually transient ( 6 months and 2C4 weeks, respectively) and the medications must be readministered if the patient’s platelet count does not stabilize.5 Repeated or prolonged administration of first\line therapies is typically not suitable due to significant adverse effects (eg, osteoporosis, diabetes, cataracts, weight gain, infections) with corticosteroids and high cost, inconvenience of frequent infusions, and debilitating post\infusion headache with immunoglobulins.4, 6, 7 Spontaneous remissions in patients who have never received treatment are uncommon in adults with ITP (9%). In many patients, the disease becomes persistent (3C12 months duration) or chronic ( 12 months duration), and second\line treatment may be needed.3, 8, 9 2.?SECOND\LINE TREATMENT Demethoxydeacetoxypseudolaric acid B analog OPTIONS Second\line or maintenance therapy in persistent or chronic ITP (hereafter referred to as ITP) aims to establish a durable platelet response and to minimize bleeding events with a treatment that is safe, tolerable, and convenient for long\term management. Splenectomy, thrombopoietin receptor agonists (TPO\RAs), and rituximab are the standard second\line treatment options in current use.3, 4 Before initiation of a second\line therapy, it is advisable to confirm the diagnosis of primary ITP by excluding potential non\immune causes of thrombocytopenia as well as causes of secondary ITP if these have not been previously ruled out. 2.1. Splenectomy Conventionally, splenectomy has been the principal option for long\term management of ITP because of its potential to induce long\term remission. Splenectomy provides a high initial response rate (85%); however, up to 30% of responders will relapse during the 10 years following an initial response (typically, within 2 years after splenectomy), and there is no widely available and reliable means of predicting whether an individual patient will respond.10 In addition, splenectomy is associated with serious short\ and long\term risks. Surgical complications were reported in 10% of patients in the 30\day period following splenectomy, even when less\invasive laparoscopic methods were used.10 Furthermore, lack of splenic function may result in infections, thromboembolism, and possibly an increased incidence of malignancy, which result in an increased risk of death that persists for 10 years after surgery.11 Based on a study of 8149 US veterans who had splenectomy for any indication, the risk of death due to certain events was 3\ to 4\fold higher in patients who had undergone splenectomy versus those with intact spleens (the risks of septicemia, pulmonary embolism, and non\Hodgkin lymphoma were 3.02\, 4.53\, Demethoxydeacetoxypseudolaric acid B analog and 4.69\fold higher, respectively).11 In addition, another study Rabbit polyclonal to ARFIP2 in 9976 patients with ITP revealed a 2.7\fold increased risk of venous thromboembolism and a 1.6\ to 3.1\fold increased risk of sepsis (depending on timing and comorbidities) 90 days after splenectomy (median follow\up of 120 months), but an increase in the risk of malignancy was not reported.12 Thus, splenectomized patients need lifelong management to prevent sepsis, such as vaccinations and prophylactic antibiotics, as well as surveillance for relapse. The advent of pharmaceutical second\line treatment options has significantly decreased the use of splenectomy in ITP.13, 14 However, splenectomy may still be preferred by some patients who desire independence from medications.15 2.2. Thrombopoietin receptor agonists Thrombopoietin receptor agonists are approved for the treatment of patients with chronic ITP who had an insufficient response to either a first\line therapy or splenectomy.16, 17 Thrombopoietin receptor agonists were developed after the US clinical trials of recombinant human thrombopoietin (rhTPO) were withdrawn because injection of a pegylated, truncated, and nonglycosylated fragment of TPO (pegylated recombinant human megakaryocyte growth and development factor) caused anti\thrombopoietin antibody development that resulted in severe thrombocytopenia.18 While the same theoretical risk exists with full\length recombinant TPO, this treatment is still being used in China and there are no Demethoxydeacetoxypseudolaric acid B analog published cases of neutralizing anti\TPO antibody development with this agent.19, 20 TPO\RAs share no structural analogy with endogenous TPO and thus are not expected to induce formation of anti\TPO antibodies.21 Moreover, they have improved pharmacological properties compared with rhTPO including more potent activation of the TPO receptor and convenience of administration.16, 17, 18, 22 In Western countries, TPO\RAs are the only widely.