Treating Hemophilia A—Research and Analysis Following SIPPET
The findings of the SIPPET study have prompted conversations about how to reduce the risk of inhibitor development in patients with hemophilia A, especially as inhibitors remain the most significant treatment challenge.
Naturally occurring factor VIII/von Willebrand factor (FVIII/VWF) derived from human plasma resulted in less inhibitor development in previously untreated patients than recombinant FVIII engineered in animal cell lines. This finding is clinically important because inhibitor development is the most severe complication in hemophilia A.1
Product choice matters to inhibitor risk1
The SIPPET results may change the way doctors plan treatment for previously untreated patients, the population studied. It is believed that the presence of VWF, when contained with FVIII, may protect against inhibitor development. Therefore, plasma-derived FVIII products containing VWF may be immunoprotective.
The Medical and Scientific Advisory Council (MASAC) updated their recommendations on plasma-derived FVIII vs recombinant FVIII treatments after the SIPPET results were published. MASAC recommends that newly diagnosed patients and their caregivers consider the new data from SIPPET, as well as all existing data on inhibitor formation in previously untreated patients and the pathogen safety risk/benefit of the 2 product classes, and the following options:
- Initiate therapy with a plasma-derived FVIII/VWF product in all previously untreated patients
- Initiate therapy with a recombinant FVIII product as previously recommended by MASAC
- Initiate therapy with a newer recombinant FVIII product
After reviewing the results of the SIPPET study, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) concluded that inhibitor development risk should be evaluated individually for all treatments, regardless of class, due to the different characteristics of individual products.
Influence on clinical practices3
The results of SIPPET have had an impact on how doctors are addressing inhibitors with their previously untreated patients. Many doctors feel that their patients with hemophilia A should be aware of the SIPPET study results. According to one web-based survey of Hematosis and Thrombosis Research Society members, a majority of respondents felt that the results of SIPPET could impact their treatment choice for previously untreated patients.
Inhibitor research and analysis continues
As more studies, reports, and analyses following SIPPET are published, they will be added so you can stay up to date.
ADDRESSING QUESTIONS ABOUT SIPPET STUDY DESIGN, METHODOLOGY, AND ANALYSIS
After the publication of the SIPPET study in 2016, people had many questions. In an effort to provide answers, the original SIPPET investigators wrote a response entitled, "SIPPET: methodology, analysis and generalizability," which was published in 2017. This article addressed the most common questions associated with the design and results of the SIPPET study.4
SIPPET used a randomized study design rather than an observational study design1,4
The study was a randomized, multicenter trial conducted in 14 countries, with well-balanced study arms.
SIPPET was the largest study ever of its kind.
251 patients were included in the final analysis.
SIPPET results are applicable to product classes, not individual brands4
The focus of the study was to determine if there was a difference between the rate of inhibitor development in each product group, not how many incidents of inhibitors occurred.
Inhibitor development rate by class
In previously untreated patients, recombinant FVIII had an 87% higher rate of inhibitor development than plasma-derived FVIII/VWF.1
Risk of inhibitor development was consistent across all variables1
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- Peyvandi F, Mannucci PM, Garagiola I, et al. A randomized trial of factor VIII and neutralizing antibodies in hemophilia A. N Engl J Med. 2016;374(21):2054-2064.
- Medical and Scientific Advistory Council. MASAC Recommendation on SIPPET (Survey of Inhibitors in Plasma-Product-Exposed Toddlers): Results and Recommendations for Treatment Products for Previously Untreated Patients with Hemophilia A. New York, NY: National Hemophilia Foundation. June 17, 2016. MASAC Document #243.
- Al-Huniti A, Ten-Eyke P, Sharathkumar A. Impact of SIPPET Study on Clinical Practice in United States: A Survey of Hemophilia and Thrombosis Research Society Members. Division of Pediatric Hematology Oncology, University of Iowa Stead Family Children's Hospital.
- Peyvandi F, Mannucci PM, Palla R, Rosendaal FR. SIPPET: methodology, analysis and generalizability. Haemophilia. 2017;23(3):353-361.