In this issue of the e-news
CONTENTS:
- Geographic Distribution of Patient and Physician ITP Treatment Preferences and Effect Of Physician Caseload On Treatment Practices: Results From The ITP World Impact Survey (I-Wish)
- Daratumumab: A New Approach for Treating Refractory Autoimmune Cytopenia
Geographic Distribution of Patient and Physician ITP Treatment Preferences and Effect Of Physician Caseload On Treatment Practices: Results From The ITP World Impact Survey (I-Wish)
It is important that patients with ITP have a say in which treatment they receive. In a continuation of the ITP World Impact Survey (I-Wish) conducted by a team of world-renowned ITP experts and patient advocates including PDSA, preferences of both physicians and patients in diverse geographical settings were analyzed as to the choice of second-line therapy after failure of corticosteroids or IVIG. The number of patients (caseload) currently treated by a physician was also taken into consideration to determine whether factors including convenience or experience in treating ITP patients also impacted physician preference. Overall, 90% of all patients surveyed prefer an oral ITP treatment over an injection, and 77% of physicians agreed. However, providers differed in specific treatment preferences depending in part on where in the world they practice. When asked about which treatment physicians preferred for trying to achieve remission for their patients, splenectomy was preferred in Canada, Colombia, and the USA; steroids were preferred in China and India; and TPO-RAs (Promacta/Revolade, N-Plate, Doptelet) were preferred in Egypt, Turkey, the UK, Spain, Italy, France, Japan, and Germany. Physicians who treated a significant number of ITP patients were more likely to prefer an oral therapy over an injectable treatment, and this treatment preference was in line with type of therapy chronic ITP patients preferred. More specifically, doctors who are more experienced with treating ITP patients have a strong preference for using TPO-RAs, and generally prescribing avoided corticosteroids. In sum, these results show that physician treatment preferences depend both on where a patient lives and on their doctor’s experience in treating ITP patients.
Comments from PDSA’s Medical Advisors:
The I-WISh survey generated a considerable amount of information from approximately 1500 patients and almost 500 physicians. The abstract described above focuses on the physician side of preferences for treatment. An important emphasis of both the ASH Guidelines and International Consensus report from December 2019 was restricting the use of steroids. This message was apparently more clearly adopted by physicians with more experience in treating patients with ITP. The reasons underlying the geographic division of preference are clear but could be related to differences in funding by region Socioeconomic features of the patients were not included in the survey and how this may have affected physicians’ choices will need more study. It is important to note that the information in the survey was not backchecked against actual practice.
Daratumumab: A New Approach for Treating Refractory Autoimmune Cytopenia
Recent studies indicate that an antibody used in the therapy of patients with multiple myeloma may also be useful in the treatment of ITP. Daratumumab is a monoclonal antibody that blocks a protein called anti-CD38 expressed on plasma cells, which contribute the production of antibodies against platelets in ITP. In a preliminary study from France, five patients with ITP were treated with weekly (between 4 and 11) intravenous infusions of Daratumumab along with dexamethasone. These patients had previously failed to respond or stopped responding to Rituximab, the anti-CD20 monoclonal antibody which targets B cells and five of the patients had been splenectomized. Three months after the initiation of treatment, the concentration of antibodies in the blood decreased significantly. Two of five patients had an increase in platelet count after 4 infusions and one was able to discontinue steroids, but relapses were seen by 9 months.
Comments from PDSA’s Medical Advisors:
Rituximab was initially developed to target at B cell malignancies, e.g., some lymphomas and chronic lymphocytic leukemia. In a few patients, a concomitant autoimmune disease improved, eventually leading to the use of rituximab in ITP. The hypothesis underling its use was as the rituximab eliminates the autoreactive B cells, the autoreactive plasma cells would die out, autoantibody levels would fall, and the platelet counts would improve. However, subsequent studies demonstrated that some of the autoimmune plasma cells had a far longer lifespan than had been anticipated, which might contribute to lack of response or relapse. In support of this, it is likely that long-lived plasma cells are responsible for the retention of plasma IgG levels following treatment with rituximab. Several approaches have been taken to inhibit autoantibody production by plasma cells, including high dose dexamethasone and bortezomib, but none has shown consistent efficacy. The failure to respond could result from insufficient reduction antiplatelet antibodies because rituximab does not target plasma cells which have low to no expression of CD40. In contrast, daratumimab targets plasma cells, but it should be noted does not target B cells. Studies with daratumimab in ITP are too preliminary to say more than that some patients respond. Response rates, duration of response, and duration of treatment remain to be established. It is clear however that unlike rituximab, hypogammaglobulinemia is frequent and IVIG replacement may be needed. It has been suggested that combining rituximab (which targets B cells) with daratumimab (which targets plasma cells) may be especially effective in lowering autoantibody levels, but the benefit and side-effects of combination therapy have not been studied.
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