Is Neonatale Screening op Mucoviscidose aangewezen in België?

8 Cystic Fibrosis Neonatal Screening KCE Reports 132
• Developing allele-specific therapies to correct the specific defects in
mutant forms of CFTR.
Class I mutations are characterized by the presence of a premature termination codon
(PTC) resulting in a truncated and often non-functional protein. Agents that suppress
the normal proof reading function of the ribosome can overcome diseases caused by
PTCs. In preclinical settings high dose aminoglycosides induce such a translational
‘read-through’ and restore protein function, 27 however the potential renal and
ototoxicity limit their clinical use. ATALUREN (formerly known as PTC124) has been
studied in healthy volunteers and in CF. 28, 29 Results of phase 2 studies have recently
been published 30 and a phase 3 study is now ongoing.
Similarly, encouraging data have been reported using VX-770 in adults with CF and at
least one copy of the mutation G551D. This “potentiator” is believed to help to open
the chloride channel in CF cells. In a randomised, double-blind, placebo-controlled
study, this agent appeared to be safe and was associated with significant improvements
in terms of the forced expiratory volume in 1 second (FEV1), nasal potential difference
measurements and sweat electrolytes. Two Phase 3 studies began in the summer of
2009.
VX-809 is a “corrector” that is expected to improve CFTR cell trafficking and its
function as a chloride channel. A large Phase 2a trial of this compound is ongoing in
patients homozygous for the F508 del mutation.
1.4 CF NEWBORN SCREENING (CF NBS) IN THIS CONTEXT
Perspectives of curative treatment have modified the objectives of CF dedicated
physicians. An important part of the challenges they are now facing is to preserve lung
function of many children (and a much smaller proportion of adults) by maximising
current treatment regimens, so that they can benefit fully from future therapies that
could correct the basic defect. 31
A number of studies using bronchoalveolar lavage (BAL) markers of infection and
inflammation but also lung function tests and more recently computed tomography of
the chest have documented that significant lung damage occurs very early in many, even
asymptomatic CF infants. 32-35
Universally coupled with immediate referral to CF centres, CF NBS has expanded
rapidly to most western countries including all US states except one within a few years.
By permitting earlier diagnosis and optimal treatment, it has the potential to be one of
the factors helping many patients to reach the key moment of “the cure discovery” with
clear enough lungs. Centre-based 36-38 and/or wider scale quality improvement
initiatives 39, 40 are obviously necessary too.
1.5 PURPOSE OF THIS REPORT
This work aimed to address the following issues around CF NBS:
• Clinical effectiveness: summary of current evidence
• Possible harms and how to minimize them
• Current guidelines for implementation and care after screening
• Belgian data: current outcome and room for improvement
• Choosing a screening algorithm
• Ethical and legal aspects
• Economical aspects
The issue of community-wide screening for cystic fibrosis carriers is beyond the scope
of this report.