Lena Hjelte, Kvalitetsregister för cystisk fibros – CF register

Cystisk Fibros – en medicinsk utmaning
Path forward
Lena Hjelte
Professor, överläkare
Stockholm CF Center
Karolinska Universitetssjukhuset
Swedish Quality Register Conference
Gothenburg, Sweden
April 12, 2016
Cystic fibrosis (CF)
Epidemiology
Clinical picture
Complications
1/56001
CF-related diabetes:
15% of CF pts8
n=670
1 Lannefors L and Lindgren A. Resp Med 2002
2 Davis PB et al., Am J Respir Crit Care Med 1996
3 Ratjen F and Doring G, Lancet 2003
4 Levy H, et al. Pediatr Pulmonol 2007
5 Wheeler WB, et al. J Pediatr 1984
6 Stephenson A, et al. Am J Clin Nutr 2007
7 Rovner AJ et al. Am J Clin Nutr 2007
Progressive pulmonary
disease2,3
•associated with chronic
inflammation4
•severity correlated with IgG
levels4,5
Liver disease
Bone disease
Azospermi
8 Mackie AD, et al., Diabet Med 2003
Pancreatic Insufficiency
-> vitamin D insufficiency6,7
Genprodukten CFTR uttrycks i epitelceller
Vid defekt funktion symtom från:
Lunga
Mag-tarm kanal
Njure
Lever
Pankreas
Reproduktions
- organ
Svettkörtlar
Behandling
•Intensiv lungbehandling innefattande fysikalisk terapi och
antibiotika
•Pankreasenzymer
•Energität kost rik på essentiella fettsyror
•Extra tillkost av fettlösliga vitaminer
•Psykologiskt stöd
•Återkommande information/utbildning
Andningsgymnastik
Inhalation (slemlösande)
Syfte: Underlätta den efterföljande
andningsgymnastiken
Andningsgymnastik
Syfte: Mobilisera och evakuera
slemmet från lungorna
Fysisk aktivitet
Syfte: befrämja konditionen, öka
bröstkorgsrörligheten
Andningsgymnastik 1963
Andningsgymnastik
Intravenös antibiotika behandling i
hemmet 1985
Strandvik B, Hjelte L, Malmborgg
AS, Widén B. Home intravenous
antibiotic treatment in cystic fibrosis.
Scand J Gastroenterol Suppl.
1988;143:119-20.
Hjelte L, Widén B, Malmborg AS,
Freyschuss U, Strandvik B.
[Intravenous administration of
antibiotics at home in patients with
cystic fibrosis improves quality of life]
Lakartidningen. 1988 May
4;85(18):1614-7.
Intermate - Homepump
Behandling
•Intensiv lungbehandling innefattande fysikalisk terapi och
antibiotika
•Pankreasenzymer
•Energität kost rik på essentiella fettsyror
•Extra tillkost av fettlösliga vitaminer
•Psykologiskt stöd
•Återkommande information/utbildning
Överlevnad - Sverige
Current and estimated survival rates of four different cohorts of Swedish CF-patients
Pulmonary function (median FEV1.0 % of predicted)
Stockholms CF Center 5 year intervals, USA yearly
Median FEV1 Percent Predicted for CF Patients ≥ 18 Years
by CF Center, 2007
100
Sthlm
4
80
3
2
1
Percent
60
40
20
0
The national median FEV1 is 63.9 percent predicted. The range is 33.9 to 92.5 percent predicted.
Framgångsfaktorer
Centraliserad vård med multidisciplinära tvärprofessionella team
– täta besök (shared care) och individualiserad behandling
Diagnostik
Svettest
Symtom förenliga med sjukdomen
Hereditet för CF
Mutationsanalys
Potentialdifferens-analys
Framgångsfaktorer
Centraliserad vård med multidisciplinära tvärprofessionella
team – med täta besök och individualiserad behandling
Nya antibiotika
Förbättrad nutrition
Förbättrad andningsgymnastik
Lung (och lever) transplantationer
Plenary Session III
NACF
Anaheim 2007-10-07
Michael P Boyle
The top ten suggestions
10. Maximize clinic time! have pre clinic meetings + plus post clinic
clean up meetings
9. Review the basics at every visit! Education. Cystic fibrosis
care form. Tell me exactly what you are doing.
8. Be kind but not too nice ! Chest 2003;123:20-27. Johnson C et
al. Normal is normal
7. When in doubt bring them back soon!
6. Involve patients in their own care by giving feedback!
pictures, figure, trends etc
The top ten suggestions, continued
5. Take advantage of available sources! for example port CF
4. The Paediatric team sets the trends!
3. Make it personal! Pry enough to identify where the obstacle is
2. It is all about team!
1. Be determined to improve!
Ett optimalt medicinskt och psykosocialt
omhändertagande
Patientsäkerhet
Hygieniska aspekter
Ständig förnyelse
CF teamet
Stockholm CF Center/CF vården som förnyare
Centraliserad vård
Först med
• Intravenös antibiotika behandling i hemmet (utan
mellanhänder) 1985
• Subcutana venportar 1986
• Intermate 1990
• Nutriplus 1996
• CF-register 1992 – web baserat 2011
Ronald McDonald Hus
Skurtfilmer – TV3
Stockholm CF Center som förnyare
Videokonferens med inremitterande sedan ca år 2000
Först med
• egen hemsida (riktad till olika åldrar etc)
• krypterat mailsystem för patienter
Första CF center i Skandinavien i ECFS-CTN
”Vår framtid” – barnen som experter
Genia” - en modell för utvecklandet
”
av vården framtagen av CF förälder
Nya läkemedel för Cystisk Fibros
CFTR - cystic fibrosis transmembrane
conductance regulator
Mutationsklasser – ”typfel i receptet för
CFTR”
% CF patient
10%
70%
2-5%
< 2%
Mutationsklasser – ”typfel i receptet för
CFTR”
% CF patient
10%
Translarna
70%
Orkambi
2-5%
Kalydeco
< 2%
Rapid and Sustained Improvement in %-Predicted
FEV1 through Week 48
ENVISION
Children
STRIVE
Adolescents/Adults
Treatment effect
through Week 24
+ 10.6 %
P < 0.0001
14
Treatment effect
through Week 24
+ 12.5 %
P < 0.001
Treatment effect
through Week 48
+ 10.5 %
P = 0.0001
P la c e b o
Iv a c a fto r
18
12
16
10
6
4
2
0
-2
-4
Da y 15
W eek 8
W e e k 16
W e e k 24
W e e k 32
Estimates are model-based. Points and 95% CI are unadjusted (raw)
Ramsey BW, et al. N Engl J Med. 2011;365:1663-72.
Davies JC. Presented at: ECFS; June 6-9, 2012; Dublin, Ireland.
W e e k 40
W e e k 48
12
10
8
(mean, ± SEM)
Absolute change in % predicted FEV1
14
8
(m e a n , 9 5 % C I)
A b s o lu te c h a n g e in % p re d ic te d F E V 1
Treatment effect
through Week 48
+ 10.0 %
P < 0.001
Placebo
Ivacaftor
6
4
2
0
-2
-4
Day 15
Week 8
Week 16
Week 24
Week 32
Week 40
Week 48
Changes from Baseline in CFQ-R Respiratory Domain
ENVISION
Children
STRIVE
Adolescents/Adults
Treatment effect
through Week 48
+ 8.6
P < 0.0001
Treatment effect
through Week 24
6.1
P = 0.1092
14
10
12
MCID
4
2
0
-2
-4
Placebo
Ivacaftor
-6
Treatment effect
through Week 48
5.1
P = 0.1354
10
8
Points (mean, ± SEM)
6
Change in CFQ-R respiratory domain score
12
8
points (mean, 95% CI)
Change in CFQ-R respiratory domain
Treatment effect
through Week 24
+ 8.1
P < 0.0001
6
MCID
4
2
0
-2
Ivacaftor
Placebo
-4
-6
-8
Day 15
Week 8
Week 16
Week 24
Week 32
Week 40
Week 48
Day 15
Week 8
Week 16
Week 24
Estimates are model-based. Points and 95% CI are unadjusted (raw) . Pooled data from Adolescent/Adult and Children versions
Established minimal clinically important differences (MCID) for respiratory domain is four2 (Quittner AL, et al. Chest. 2009;135: 1610–8).
Ramsey BW, et al. N Engl J Med. 2011;365:1663-72.
Davies JC. Presented at: ECFS; June 6-9, 2012; Dublin, Ireland.
Week 32
Week 40
Week 48
Change From Baseline in Sweat Chloride
ENVISION
Children
STRIVE
Adolescents/Adults
Treatment effect
through Week 48
–48.1 mmol/L
P < 0.0001
Treatment effect
through Week 24
–47.9 mmol/L
P < 0.0001
Placebo
Ivacaftor
mmol/L (mean, 95% CI)
-10
-20
-30
-40
-50
-60
Placebo
Ivacaftor
0
-10
mmol/L (mean, ± SEM)
0
Treatment effect
through Week 48
–53.5 mmol/L
P < 0.0001
10
Change in sweat chloride concentration
10
Change in sweat chloride concentration
Treatment effect
through Week 24
–54.3 mmol/L
P < 0.0001
-20
-30
-40
-50
-60
-70
-70
Day 15
Week 8
Week 16
Week 24
Week 32
Week 40
Estimates are model-based. Points and 95% CI are unadjusted (raw)
Ramsey BW, et al. N Engl J Med. 2011;365:1663-72.
Davies JC. Presented at: ECFS; June 6-9, 2012; Dublin, Ireland.
Week 48
Day 15
Week 8
Week 16
Week 24
Week 32
Week 40
Week 48
Weight z-scores
ENVISION
Children
STRIVE
Adolescents/Adults
(mean, ±SEM)
Weight-for-age z-scores
Treatment effect
through Week 24
+ 0.32
P = 0.0004
Treatment effect
through Week 24
+ 0.27
P = 0.0001
Treatment effect
through Week 48
+ 0.33
P = 0.0260
1.0
1.0
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
-0.0
-0.0
-0.2
-0.2
-0.4
-0.4
-0.6
-0.6
-0.8
-0.8
-1.0
Treatment effect
through Week 48
+ 0.39
P < 0.0001
-1.0
8
16
24
32
40
8
16
24
32
Week
Week
Placebo
n=23
48
Ivacaftor
n=24
Estimates are model-based. Points and 95% CI are unadjusted (raw)
Ramsey BW, et al. N Engl J Med. 2011;365:1663-72.
Davies JC. Presented at: ECFS; June 6-9, 2012; Dublin, Ireland.
Placebo
n=26
Ivacaftor
n=26
40
48
BMI z-scores
ENVISION
Children
STRIVE
Adolescents/Adults
(mean, ±SEM)
BMI-for-age z-scores
Treatment effect
through Week 24
+ 0.34
P = 0.0010
Treatment effect
through Week 24
+ 0.34
P = 0.0002
Treatment effect
through Week 48
+ 0.33
P = 0.0490
1.0
1.0
0.8
0.8
0.6
0.6
0.4
0.4
0.2
Treatment effect
through Week 48
+ 0.45
P < 0.0001
0.2
-0.0
-0.0
-0.2
-0.2
-0.4
-0.4
-0.6
-0.6
-0.8
-0.8
-1.0
8
16
24
32
40
Placebo
n=23
48
-1.0
8
Week
Ivacaftor
n=24
Estimates are model-based. Points and 95% CI are unadjusted (raw)
Ramsey BW, et al. N Engl J Med. 2011;365:1663-72.
Davies JC. Presented at: ECFS; June 6-9, 2012; Dublin, Ireland.
16
24
32
Week
Placebo
n=26
Ivacaftor
n=26
40
48
DeltaF508 mutation – den vanligaste mutationen
% CF patient
10%
70%
2-5%
< 2%
Theoretical model of CFTR structure.
Serohijos A W R et al. PNAS 2008;105:3256-3261
©2008 by National Academy of Sciences
DeltaF508 mutation – den vanligaste mutationen
% CF patient
10%
70%
Orkambi
2-5%
< 2%
Nya läkemedel
• Dyra 1.5 – 2 milj Skr/år
• Individuella svar
• Uppföljning/utvärdering krävs
• Ev biverkningar