Efficacy and tolerability of old and new drugs used in the treatment of immune thrombocytopenia: Results from a long-term observation in clinical practice.

BACKGROUND: Many patients with immune thrombocytopenia (ITP) may require special attention and long-term treatment. Little is known on the efficacy and tolerability of the drugs used in practice. MATERIAL AND METHODS: We retrospectively reviewed the results of therapy of 400 patients with chronic ITP. All Patients were treated at our institution between 1996-2016 under consideration of guidelines, general recommendations, and individual aspects, including gender, age, weight, comorbidity, patient's medical history and bleeding risk. RESULTS: Treatment was not required in 25% of patients (n = 100) during observation. In treated patients (n = 300), the rate of patients that responded and tolerated treatment with prednisolone was 59% (52/88), with azathioprine 32% (29/90), with eltrombopag 49% (31/63), with romiplostim 59% 27/45, with IVIG (intravenous immunoglobulines) 75% (94/126), with anti-D 37% (19/52) and with dexamethasone 60% (25/42) patients. Eighteen treated patients (6%) entered sustained remission after treatment with various drugs. Twenty-six patients underwent splenectomy (Splx) resulting in sustained remission in 15 cases (60%). Only two patients remained refractory to Splx and to all used drugs. DISCUSSION: None of the currently available drugs used in the treatment of ITP are invariably safe and effective. Responses, the duration of response, intolerability, and the course of disease are unpredictable. Although the treatment of ITP has considerably improved in the recent years, the currently available drugs may rarely cure affected patients. The need for safe and effective therapy in ITP is evident. Optimal treatment decisions for each patient remains a challenge in many cases.

Bidirectional inefficacy or intolerability of thrombopoietin receptor agonists: new data and a concise review.

BACKGROUND: There is evidence that the thrombopoietin-receptor agonists romiplostim and eltrombopag may have different therapeutic values and adverse reaction profiles. Here we present new data and provide a review of all studies dealing with switching between these two drugs. MATERIALS AND METHODS: A total of 89 patients (38 males and 51 females, aged between 14-87 years) were treated with eltrombopag and/or romiplostim between 2007 and 2016 at our institution. Eltrombopag was switched to romiplostim or vice versa in 32 patients. In addition, all published data concerning patients treated sequentially with different thrombopoietin-receptor agonists were identified via a computer-assisted search and summarised in this article. RESULTS: Thirty-two of 89 patients treated with a thrombopoietin-receptor agonist in our institution were given both eltrombopag and romiplostim sequentially. Therapy was switched to the alternate thrombopoietin-receptor agonist 36 times, due to inefficacy (n=21), adverse reactions (n=14), and a patient's preference (n=1). In addition, data from 126 patients who have been treated with both agonists have been published by other groups. In total eltrombopag was replaced by romiplostim in 56 cases due to poor or no response or to adverse reactions. Forty-five patients responded to treatment with romiplostim, 11 patients shared cross-resistance and nine had adverse reactions to romiplostim. In contrast, romiplostim was replaced by eltrombopag in 106 cases. Seventy-eight patients responded to eltrombopag, 27 shared cross-resistance and 19 had adverse reactions to eltrombopag. DISCUSSION: Eltrombopag and romiplostim often share bidirectional cross-resistance and/or adverse reactions. Both drugs appear to cause more adverse reactions than have been previously reported.

Is Autoimmune Thrombocytopenia Itself the Primary Disease in the Presence of Second Diseases Data from a Long-Term Observation.

BACKGROUND: Dependent on the absence or presence of associated diseases, autoimmune thrombocytopenia (ITP) can be classified as primary or secondary form. The manifestation of the associated diseases is not temporally defined and may occur during observation. Thus the question which disease is the primary one remains unanswered. METHODS: All 386 patients included in this study were treated by a single primary physician between 1996 and 2015 at the Charité Berlin and met current ITP criteria. Medical records and investigations were reviewed to assess diseases associated with ITP. RESULTS: Initially, the vast majority of patients presented with primary ITP (isolated disease). Based on our findings, ITP was found to be associated with other abnormalities in most cases. These abnormalities included: positive direct antiglobulin test in 49 of 386 tested patients (13%), affections of the thyroid gland in 41 of 386 tested patients (11%), infections in 30 (8%), solid malignancies in 20 (5%) and hematological malignancies in 10 patients (3%), as well as many other miscellaneous diseases. Moreover, of 160 patients who did not receive prior intravenous immunoglobulin treatment, 40 (25%) showed antibody deficiency. CONCLUSION: In conclusion, the incidence of 'true' ITP as a primary disease is less common than has yet been suggested. Additionally, there is evidence that ITP itself predispose affected subjects toward development of other diseases.

Thrombopoietin Receptor Agonists Are Often Ineffective in Immune Thrombocytopenia and/or Cause Adverse Reactions: Results from One Hand.

BACKGROUND: Eltrombopag and romiplostim are thrombopoietin receptor agonists (TPOs) that have been increasingly used for the treatment of immune thrombocytopenia (ITP). Based on our experience, the incidence of abortive treatment with these drugs and the occurrence of adverse reactions that lead to therapy break-off despite response are higher than has been previously suggested. METHODS: During the last 8 years, a total of 65 patients were treated with eltrombopag and/or romiplostim at our institute. RESULTS: 36 of a total of 58 patients responded well to eltrombopag. In 12 patients that responded, treatment with eltrombopag was discontinued due to the development of adverse reactions. Eltrombopag was replaced by romiplostim in 23 cases (14 non-responders, 9 patients with adverse reactions). Of these patients, 83% responded to romiplostim. Among all patients treated with romiplostim (n = 32), 75% initially responded; however, 8 of these patients developed adverse reactions. Romiplostim was replaced by eltrombopag in 5 cases (4 due to adverse reactions, 1 non-responsive patient), and only 3 (60%) of these patients were observed to respond to eltrombopag. CONCLUSION: TPOs often remain ineffective in ITP or result in adverse reactions, which lead to treatment stop or to drug switch. Therefore, alternative treatment options are required.