PDSA e-News: February 23, 2021

In this issue of the e-news, we report on research contributed to the 62nd ASH Annual Meeting and Exposition by PDSA staff and advisors in addition to research from external researchers showcasing patients’ overall quality of life living with ITP, a promising future ITP treatment, and risk factors for older ITP patients.


Impact of Therapy Choice on Fatigue in Adults with Immune Thrombocytopenia

Tired woman on sofaIn this study, self-reported fatigue and its impact among adult ITP patients was examined to determine whether fatigue levels differ depending on treatment status. To collect this information, surveys from the PDSA Natural History Study Registry were used. Patients were stratified based on: 1) no treatment received, 2) treated in the past, or 3) on therapy within the last six months; patients currently on therapy were further stratified by first and second-line therapy. Among the 357 completed surveys on treatment history, 11% (n=40) of the patients reported they never received treatment for their ITP, while 46% (n=166) had in the past, and 43% (n=158) were currently receiving therapy (within the last six months). Among those currently on treatment, 82% of the patients were receiving monotherapy; 47 (26%) as a first-line therapy (corticosteroid, IVIG, or Anti-D), and 78 (43%) as a second-line therapy (TPO-RA, rituximab, and other second-line options). Therapies reported included: TPO-RA’s (41%), corticosteroids (24%), IVIG (7%), rituximab (3%), SYK inhibitor (1%), antibiotics (4%), anti-D (1%), other second-line treatments (such as MMF, dapsone etc.), and “other” therapies including complementary treatments (14%). Overall, 93 (23%) reported having had a splenectomy.

When asked to reflect on general tiredness, 98% of patients (n=310) reported being tired on at least some occasions, with 55% reporting feeling tired ‘almost always/often’ irrespective of treatment or treatment history. Those who had never been treated reported they felt tired 94% of the time, and 55% reported feeling tired ‘almost always/often’. Among those not currently on treatment (but received therapy in past), 99% reported feeling tired on at least some occasions overall, and 50% reported feeling tired ‘almost always/often’. 100% of respondents currently being treatment with a first line therapy reported feeling tired on at least some occasions, and 53% reported feeling tired ‘almost always/often’. Respondents using a second line therapy reported feeling tired 99% of the time, and indicated they were tired 59% ‘almost always/often’. There were no significant differences between treatment types or groups included in this study.

When asked to reflect on the level of fatigue over the seven days preceding, collectively 86% reported fatigue, and 30% reported experiencing it ‘very much/quite a bit’. Among those who had never been treated, 85% reported fatigue, and 27% indicated they felt fatigue ‘very much/quite a bit’. Respondents who were not receiving treatment reported feeling fatigue 84% of the time, with 26% experiencing ‘very much/quite a bit’ of fatigue. Among those receiving a first line therapy, 90% reported fatigue in the preceding seven days, and 34% reported they experienced this ‘very much/quite a bit’. Those using a second line therapy reported feeling fatigue 91% of the time, and 29% reported this was ‘very much/quite a bit’. There were no significant differences among these treatment types or treatment groups within the study.


Comments from PDSA’s Medical Advisors:

Reports of fatigue and tiredness are remarkably high among all patients with ITP, including those currently on treatment, those not on treatment, and even those who had never been treated. The severity of fatigue is unrelated to disease activity defined by the need for active treatment or, equally remarkably, treatment type and seemingly response based on platelet count alone. The cause of fatigue in this population appears to be quite complex and seemingly involves a combination of factors associated with having an unpredictable chronic disease in addition to standard measures of disease activity and side effects of treatment. Unfortunately at this time the underlying etiology of fatigue and the optimal strategy to alleviate it remain uncertain.

Long-term Safety and Efficacy of Sutimlimab in Patients with Chronic Immune Thrombocytopenia

doctor with clipboardThis phase one study reports on the safety and efficacy (the ability to work) of a first-in-class humanized monoclonal antibody, Sutimlimab (previous called BIVV009), in twelve adult patients with chronic ITP (cITP) diagnosed at least 12 months prior to participation. Sutimlimab works by inhibiting a complement component in what is called the classic complement pathway. Complement is a part of how the immune system amplifies the effects of antibodies. If the antibodies in question are anti-platelet antibodies, then inhibiting complement could lessen the effect of the antibodies and thus increase the platelet count.

Eligible adults with cITP were required to have a baseline platelet count below 30,000/µL who previously had an inadequate response to at least two other ITP therapies. There were some participants who were receiving a stable dose of an ITP therapy in addition to the Sutimlimab in order to maintain a minimum platelet count of 30,000/µL without bleeding. The study was divided into two parts. In part A, participants received the drug for up to 21 weeks on a pre-specified schedule followed by 9 weeks off the drug. In part B, participants who had a meaningful response to the drug and did not require rescue therapy for bleeding in part A were then re-treated in the long-term extension phase. Four participants were removed due to insufficient response or a need for rescue therapy. Six participants completed part B.

Results revealed that of the 12 patients who were previously ‘refractory’ to TPO-RAs, rituximab, and splenectomy, were able to achieve an initial rapid increase in their platelet counts with a doubling of the mean platelets count, remarkably within 24 hours of using the drug. The mean platelet count increased to over 50,000/µL by day one and was maintained for the duration of treatment. Overall 41.7% of patients achieved a durable response using the drug as a monotherapy. There were no deaths or thromboembolic events during the study, and none of the participants discontinued the drug due to an adverse event.


Comments from PDSA’s Medical Advisors:

This phase one study indicates that, as expected, the classical complement pathway plays an important pathophysiologic role in a subset of patients with cITP, especially those with severe refractory disease (although we suspect that complement is important in the majority of cases). The dramatic and remarkably rapid response to Sutimlimab in some patients supports further investigation of this drug, including biomarkers to identify those patients who are most likely to benefit.

Risk and Prognostic Factors for Intracranial Hemorrhage in Elderly Patients with Immune Thrombocytopenia

Elderly handsIntracranial hemorrhage (ICH) is the most devastating potential complication associated with immune thrombocytopenia (ITP). As such, researchers are always looking for ways to predict who is at risk in order to mitigate or prevent ICH. In this retrospective multi-center case-controlled study, elderly patients with ITP over the age of 60 years who had had an ICH were enrolled in this study to determine risk and prognostic factors. To identify if there is a subset of elderly patients more at risk for an ICH who should receive preventative therapy, a total of 44 eligible participants with primary ITP in different phases of disease were recruited. Once outcome data was analyzed using a sophisticated statistic approach, the investigators found that participants with diabetes mellitus had a low risk for developing ICH as did participants were were over the age of 75 years. Independent risk factors in elderly patients over the age of 60 years revealed included: having a platelet count less than 25,000/µL, experiencing head trauma, diagnosis of ITP within the preceding seven days, and a previous history of life-threatening bleeding. The risk was also increased in those with hematuria, GI bleeding, oral mucosal blisters, and skin bleeding.


Comments from PDSA’s Medical Advisors:

This study should help hematologists and other health care providers to identify elderly patients who are at highest risk for ICH and therefore might benefit from additional surveillance and/or more intense treatment. Patients are followed and the ones developing ICH are compared to the ones who don’t. Independent risk factors included those previously known: low platelet count, head trauma, serious bleeding, and the other one is recent diagnosis of ITP (7 days). These factors were used to create a risk score which determined not only who was at risk of ICH but also how soon it would occur. The high risk group almost all developed ICH (11/13) and one third of the intermediate risk group (27/74) did. However the low risk group (none of the 4 risk factors) had few patients (6/45) develop ICH eventually. The low risk group also seemed not to continue to be at risk and their curve seemed to flatten out after 8 years of ITP but the numbers were small that far out. Before applying this generally it is important to remember that different genetics, diet and other environmental factors might alter the translation of this study to other populations.


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