PDSA E-News: January 25, 2023


The 64th American Society of Hematology (ASH) Annual Meeting and Exposition was held as a hybrid event in New Orleans, Louisiana, December 10-13, 2022. As usual, the meeting attracted thousands of clinicians, scientists, industry partners, and even investment analysts worldwide to share ground-breaking research in the field of hematology. Here are two of the abstracts presented at ASH. Look for additional summaries of research presented at ASH in our next edition of The Platelet News, available to all PDSA members.

Efgartigimod Treatment in Adults with Primary Immune Thrombocytopenia

Patient in doctor's officeEfgartigimod (EFG) is a compound that blocks a cellular protein called the neonatal Fc receptor (FcRn). FcRn is involved in recycling IgG antibodies that enter cells back into the blood. This recycling protects the IgG antibodies from degradation and removal and thereby enhances their lifespan. In immune thrombocytopenia (ITP), abnormal IgG autoantibodies that target platelets for destruction are normally recycled as are all other IgG molecules. EFG blocks FcRn-mediated recycling of IgG antibodies which reduces the level of total IgG and, in particular, the level of IgG anti-platelet autoantibodies below that which is needed to cause platelet destruction.

This study assessed how well EFG worked and how safe it is for adults with chronic or persistent ITP. Most participants had chronic ITP and a median (middle range among participants) platelet count of 17,000/µL with over two-thirds having tried at least three prior therapies before using EFG.

Among those with chronic ITP, a greater proportion achieved a sustained platelet count response of 50,000 or higher in the last 10 weeks of the trial in the EFG group (21.8%) compared to those who received the placebo (5.0%). Placebo is where a non-medicine is given to a participant in place of the actual medicine. On average, among those with persistent ITP, participants receiving EFG had significantly and substantially longer durations of elevated platelet counts above 50,000 compared to those receiving a placebo.

Similar proportions of side effects were reported among those who received EFG (93.0%) and placebo (95.6%). The most common side effects reported included bruising, headache, hematuria (blood in urine), and petechiae. Serious adverse events (internal bleeding, infections, and ITP worsening) were observed in 8.1% of those in the EFG group and 15.6% in the placebo group. None of these serious side effects were judged to be treatment-related.



Comments from PDSA Medical Advisors

This abstract was one of six chosen from among thousands by the American Society of Hematology (ASH) abstract committee and was introduced at ASH by Dr. Douglas Cines, one of PDSA’s medical advisors. EFG is among a number of treatments used to block FcRn with the hope that it will lower levels of IgG antiplatelet antibodies below that needed to cause ITP. Of note, changes in antibody levels were not measured in the study and it is not understood why only a minority responded as every subgroup of ITP patients in the study did better on EFG than on placebo. Dosing was not randomized, but ten patients on treatment were able to reduce their treatment to every other week and nine maintained their responses on every other week dosing. The exact role of EFG and other approaches to blocking FcRn in the management of ITP is encouraging but more work needs to be done.

The Relationship Between Immune Thrombocytopenia (ITP) Outcome and Obesity

Person rolling up tape measureIn this study, the relationship between obesity (being significantly overweight) and primary immune thrombocytopenia (ITP) was assessed.

Data was collected from clinical inpatient electronic health records of 275 adults with primary ITP between May 2012 – May 2022 at the Montefiore Medical Center. Records of individuals with secondary ITP were excluded. Participants were stratified into the following four groups based on their body mass index (BMI) classification by the World Health Organization: 1) ‘normal’ weight, 2) moderately overweight, 3) significantly overweight (obese) with/without health complications, and 4) extremely overweight (morbidly obese) with/without medical complications.

Obese and morbidly obese participants had a lower average platelet count at diagnosis (21,000 – 57,000) compared to those who were not significantly overweight (81,000). Obese and morbidly obese participants also had lower platelet counts throughout the course of the disorder. Participants who demonstrated a higher BMI required more treatment to maintain their platelet levels compared to those of normal weight. The average number of treatments (or lines of treatment) increased as participants’ BMI increased, as did the percentage of patients who were steroid dependent.

Among participants who received corticosteroids as first-line therapy, those who were obese or morbidly obese experienced a shorter remission of platelet symptoms after treatment, compared to those who were not overweight at various follow-ups. There were no significant differences among all four groups in terms of the level of response to steroids, time to respond to steroids, refractoriness to steroids, or bleeding complications.

In summary, being significantly overweight was associated with a lower platelet count, an increased use of treatments including the need to use more than one therapy (multiple lines of treatment), a trend towards greater steroid dependency, and a shorter duration of post-treatment responses. Thus, obesity in this study was shown to be a risk factor for ITP-related complications that are associated with a low platelet count and its management.



Comments from PDSA Medical Advisors

This interesting study is not without precedent and a strength is the inclusion of the four categories of weight.1 While the mechanism (how it works) is unclear, the authors imply this is not due to inadequate dosing in higher-weight individuals. One possibility involves the effects of “adipokines” (small molecules released from fat cells) that might impair platelet production or enhance clearance of antibody-coated platelets by macrophages. At the presentation of this abstract at ASH, the author indicated that they will be testing the level of at least one adipokine and also had not considered the potential effects of atorvastatin to improve steroid responsiveness. It would be an important next step to show weight reduction improves responsiveness.

Hanafy E, Pakra MA. Immune Thrombocytopenia and Obesity: Predictive Relationship. Ochsner J. 2017;17(1):115-117.



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