12th September 2017

Landmark studies build evidence for widespread adoption of pre-eclampsia test

 

  • Data presented by Dr Manu Vatish at ISSHP (International Society for the study of Hypertension in Pregnancy) Congress confirms test’s ability to provide improved clinical care to patients with suspected pre-eclampsia than the previous patient pathway1
  • Five other peer-reviewed studies clarify cost and health benefits of the use of Roche Diagnostics’ Elecsys® sFlt-1/PlGF blood test to assess impending danger to mother and foetus2-6

 

LONDON, UK (12 September 2017) – Data from the recently completed randomised controlled trial has been presented at the ISSHP European Congress this September in Berlin, Germany. This interventional study evaluated the real life performance and clinical utility of the Roche Elecsys sFlt-1/PlGF ratio test in the guidance of admission of patients with suspicion of pre-eclampsia (PE) – a life-threatening condition for pregnant women.1 The authors of the INSPIRE study found that its use in combination with current clinical guidelines allows the safe discharge of patients who will not develop PE while increasing the proportion of PE patients who are admitted.1

 

Observational clinical studies published in 2016, have documented the benefits that the use of the sFlt-1/PlGF blood test ratio could offer to patients, clinicians and the NHS.2,4-6 The studies show that the ratio test can provide clinically useful information on the risk of impending danger to mother and foetus.2-6

 

An economic assessment published by Dr Vatish in Ultrasound in Obstetrics & Gynecology 2016 found that widespread adoption could produce savings equivalent to £344 per case3 and further savings are realised from freeing up beds and clinicians’ time.7

 

Hypertensive disorders, such as PE, currently affect approximately 13.5 per cent of pregnancies in the UK7 and it is estimated that as many as 80,000 pregnant women are investigated for suspected PE7. Before the test was made available, treatment guidelines recommended that all women presenting with hypertension and proteinuria should be considered for admission to hospital for monitoring, although most would not go on to develop the condition8. This unnecessary hospitalisation of women caused undue stress and anxiety for mothers, as well as significant costs to hospitals and the NHS.  

 

The ratio test, offered by Roche Diagnostics, was recommended by NICE in May 2016 to rule out women at risk.9 The test allows healthcare professionals to conduct a simple blood test and determine whether an individual patient will develop PE over the next week, with 99.3 per cent accuracy (95% confidence interval [CI], 97.9-99.9).10 Women deemed not at risk could safely return to community care.  

 

The INSPIRE study recruited 369 patients, of whom 185 were assigned to the reveal group (where the sFlt/PlGF ratio was known) and 184 to non-reveal (where the test result was not released by the laboratory).1 Analysis showed that within admitted patients, there was a reduction of 34% in those deemed to be low risk (ratio ≤38), by using the test.1 Importantly, no discharged patients in either group with a ratio ≤38 developed PE within 7 days (256 patients in total).1 Furthermore, there was also an increased admission of patients who developed PE within 1 week in the reveal group and thus use of the test enriched the PE population of patients in hospital, without increasing the overall admission rate.1 This ultimately ensured that those who needed a high level of care received it, while others were able to safely return home.

 

The study showed that the sFlt-1/PlGF ratio test has a performance in real life, which confirms previous findings from observational studies, particularly in its high negative predictive value.1 Its use in combination with current clinical guidelines for hypertension enables the safe discharge of patients who will not develop pre-eclampsia while increasing the proportion of pre-eclampsia patients who are admitted.

 

Paul Skingley, Director of Centralised Solutions, Roche Diagnostics, said:

 

“It’s hugely encouraging to see a bank of evidence for the ever-growing benefits of the Roche Diagnostics Elecsys test. Following its inclusion in the NICE guidance last year, we have been communicating the advantages that the test can offer to clinicians, and it is clear that the test can offer a great deal in contributing to cost savings and increasing efficiencies in the NHS, as well as providing a superior care pathway for pregnant women who presented with suspected pre-eclampsia.”

 

 – Ends – 

 

The studies

Vatish, M et al. ‘INSPIRE: Interventional Study Evaluating the Short-Term Prediction of Pre-eclampsia / Eclampsia in Pregnant Women with Suspected Pre-eclampsia’1

Data presentation at ISSHP 2017 European Congress, Berlin, Germany.

The randomised controlled trial evaluated the real life performance and clinical utility of sFlt/PlGF ration in the management/guidance of admission of patients with suspicion of pre-eclampsia.1

 

Klein, E et al. PreOS: ‘Influence of the sFlt-1/PlGF Ration on Clinical Decision Making in Women with Suspected Pre-eclampsia’2

PLoS ONE 2016; 11(5):e0156013

The study guided physicians on the need for hospitalisation and the appropriate intensity of clinical procedures, demonstrating that the ratio can be a useful aid for clinical decision making in real-world clinical practice.
It found:

  • In 16.9% of mothers (20/188) the hospitalisation decision was changed after knowledge of the ratio.
  • In 13 women (11%) the initial decision to hospitalise was changed to no hospitalisation.
  • In seven women (5.9%) the revised decision was hospitalisation.
  • All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p<0.0001).2

 

Vatish, M et al. ‘The sFlt-1/PlGF Ratio Test in Pre-eclampsia: An Economic Assessment for the UK’3

Ultrasound Obstet Gynecol 2016 Dec; 48(6): 765-771

Vatish et al used an economic model estimating the incremental value of information, from a UK NHS payer’s perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The researchers found that introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in costs savings of £344 per patient compared with a no-test scenario, and an annual cost saving for the NHS of £24 million. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalisation. It also found that use of the sFlt-1/PlGF ratio can be expected to reduce hospitalisation rates from 36% to 16%.3

 

Zeisler, H et al. ‘Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio and Time to Delivery in Women With Suspected Pre-eclampsia’4

Obstet Gynecol: August 2016. 128(2): 261-269

The study, a secondary analysis of an observational cohort study of women with suspected pre-eclampsia found:

  • Women with an sFlt-1/PlGF ratio >38 (n=250) had a 2.9 fold greater likelihood of imminent delivery (i.e. on the day of test) (Cox regression hazard ration 2.9; p<0.001).
  • Women with an sFlt-1/PlGF ratio >38 also had a 38% shorter remaining time to delivery (median 17 [IR10-26] vs 51 [IR30-75]; Weibull RF 0.62; p<0.001) than women with a ratio of ≤38, regardless of whether they developed pre-eclampsia.
  • The pre-term birth rate for women with sFlt-1/PlGF ratios of >38 and ≤38 were 71.2% vs 17.8% respectively.4

 

Perales, A et al. ‘sFlt-1/PlGF for Early Onset Pre-eclampsia Prediction: STEPS (Study of Early Pre-eclampsia
in Spain)’5

Ultrasound Obstet Gynecol 2016 Nov 24; doi: 10.1102/uog. 17373

During the study, the sFlt-1/PlGF ratio was found to improve prediction of early-onset pre-eclampsia for women at risk of the syndrome. The prospective, multi-centre study in Spain concluded that a developed prediction model for early-onset pre-eclampsia was superior to models using the sFlt-1/PlGF ratio alone or uterine artery mean pulsatility index.5

 

Sovio, U et al. ‘Prediction of Pre-eclampsia Using the Soluble fms-Like Tyrosine Kinase 1 to Placental Growth Factor Ratio: A Prospective Cohort Study of Unselected Nulliparous Women’6

Hypertension 2017 Apr; 36(4): 731-738

Among a population of nulliparous women at mixed risk of developing pre-eclampsia, the research found:

  • An sFlt-1/PlGF ratio >38 at 28 weeks of gestational age identified women with a high risk (>30%) of subsequently delivering preterm with pre-eclampsia.
  • An sFlt-1/PlGF ratio >110 at 36 weeks of gestational age identified women with a high risk (>30%) of subsequently experiencing severe pre-eclampsia.
  • An sFlt-1/PlGF ratio between >38 and >110 at 36 weeks of gestational age was only associated with a high absolute risk (>20%) of subsequently experiencing severe pre-eclampsia if the mother had additional risk factors.6

 

References

  1. Vatish, M et al. ‘Interventional Study Evaluation the Short-Term Prediction of Pre-eclampsia / Eclampsia in Pregnant Women with Suspected Pre-eclampsia – INSPIRE Study’. Data presented at ISSHP Congress in Berlin, Germany. 7 September 2017.
     
  2. Klein, E et al. PreOS: ‘Influence of the sFlt-1/PlGF Ration on Clinical Decision Making in Women with Suspected Pre-eclampsia’ PLoS ONE 2016; 11(5):e0156013.
     
  3. Vatish, M et al. ‘The sFlt-1/PlGF Ratio Test in Pre-eclampsia: An Economic Assessment for the UK’ Ultrasound Obstet Gynecol 2016 Dec; 48(6): 765-771.
     
  4. Zeisler, H et al. ‘Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio and Time to Delivery in Women With Suspected Pre-eclampsia’. Obstet Gynaecol: August 2016. 128(2): 261-269.
     
  5. Perales, A et al. ‘sFlt-1/PlGF for Early Onset Pre-eclampsia Prediction: STEPS (Study of Early Pre-eclampsia in Spain)’ Ultrasound Obstet Gynecol 2016 nov 24; doi: 10.1102/uog. 17373.
     
  6. Sovio, U et al. ‘Prediction of Pre-eclampsia Using the Soluble fms-Like Tyrosine Kinase 1 to Placental Growth Factor Ratio: A Prospective Cohort Study of Unselected Nulliparous Women’ Hypertension 2017 Apr; 36(4): 731-738.
     
  7. Data on File: DOF_sFlt/PIFGb_05_16 [Adapted from National Institute for Health and Care Excellence (2016) PlGF based testing to help diagnose suspected pre-eclampsia (DG23). Resource impact template. Estimated from prevalence of women with gestational hypertension (13.5% of births), live birth rate in the UK as a whole, and the proportion of women with suspected pre-eclampsia who are between 20 and 34 weeks (75%)].
     
  8. Rana, S., Powe, C.E., Salahuddin, S., Verlohren, S., Perschel, F.H., et al. (2012). Angiogenic factors and the risk of adverse outcomes in women with suspected pre-eclampsia. Circulation 125(7), 911-919.
     
  9. National Institute for Health and Care Excellence (2016) PlGF-based testing to help diagnose suspected pre-eclampsia (Triage PlGF test, Elecsys immunoassay sFlt-1/PlGF ratio, DELFIA Xpress PLgf 1-2-3 test, and BRAHMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio) NICE guideline DG23.
     
  10. Zeisler H, Llurba E, Chantraine F, et al. (2016). Predictive value of the sFlt-1:PlGF ratio in women with suspected pre-eclampsia. N Engl J Med;374:13-22.
     
  11. Verlohren S, Herraiz I, Lapaire O, et al. (2014). New gestational phase-specific cut-off values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for pre-eclampsia. Hypertension 63: 346-52.
     
  12. Verlohren, S, Herraiz I, Lapaire O, et al. (2012). The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in pre-eclamptic patients. Am J Obstet Gynecol 206, 58:e1-8.

 

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry eight years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2016 employed more than 94,000 people worldwide. In 2016, Roche invested CHF 9.9 billion in R&D and posted sales of CHF 50.6 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

 

About the pre-eclampsia test

The pre-eclampsia test, called Elecsys® sFlt-1/PlGF immunoassay ratio, assesses the ratio of two proteins sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor) found in the mother’s blood. An sFlt-1/PlGF ratio of 38 and below can rule out the development of pre-eclampsia within the next week with a negative predictive value of 99.3%, whilst a ratio above this cut off value predicts the development of pre-eclampsia within four weeks with a positive predictive value of 36.7%.10 The ratio had previously already been used as an aid in the diagnosis of pre-eclampsia and its associated adverse outcomes for mother and baby.8,11,12

All trademarks used or mentioned in this release are protected by law.