Nintedanib in CTD ILD Rationale and evidence on The Efficacy .pdf

Nintedanib in CTD ILD Rationale and evidence on The Efficacy

1. 000
Welcoming the Era of Pulmomlogy
and Critical Care in Internal Medicine
Nintedanib in Connective Tissue Disease-
Interstitial Lung Diseases (CTD-ILD):
Rationale and Evidence on the Efficacy
Iceu Dimas Kulsum
RS Hasan Sadikin Bandung
23-24 WV
2024

2. Corticosteroids have shown evidence of benefit in non-fibrotic HP but not
in fibrotic HP
Mny patients with SSc-lLD SSc-lLD
as or arrent* effect*'
wit' re 'Bed VEtu
• h d eth• rnc&t/
sscqw
CFC. AZA
Chronic use of is
an incrused
SSc •ano SK
treüd •Mth •nth tog
SE to
SAC'

3. Immunomodulatory and antifibrotic treatments
for SSc.lLD and other CTD-lLDs act on a range of biological pathways

4. Estimated 13-40% of patients with different
types of ILDs develop a chronic progressive fibrotic phenotype
Percentage of patients who develop a chronic progressive fibrotic phenotype•

5. iöR4
Patients with CTD-lLDs should be closely
monitored for the onset of progression, to enable early treatment
The active monitoring Of all patients with CTD•lLDs will help to:
pati«tts with a provesss•e earlie
treatment with nint&lib upon kientirr.atül of tt' g*motype pati«ts wit'
ILDs associated with CTDs
A&iress miscontMkxvs relat«f to by initiatng n:
• •at•o other sons ot 'LD
• sun mantanro
Pot«tialty imprm•e wtcomes beyond reåjctim of FE ±c5ne irr11Æirv
and Eute enc«batiME
• IPFO

6. 000
Nintedanib is the only antifibrotic approved
for the treatment of SSc-ILD and chronic fibrosing ILD with a progressive
phenotype, which includes CTD-ILD with a progressive phenotypel-s
Nintedanib is a multitargeted
TKI MitifibfOtiC ano-nnynrrøt«y
properties that key tibrobc pathwm
to
Nintedanib is approved for the
treatment of IPF, SSc-lLD
and chronic fibrosing ILD with
a progressive phenotype,
which includes CTD-lLDs with
a progressive phenotype'-3

7. Consistently slowed FVC decline in CTD.ILDs
in INBUILD@, irrespective of use of DMARDs and/or glucocorticoids•
Annual Of in in by of DUARDs in

8. Magnitude of the problem in CTD-ILD: SSc-lLD
ILD prevalence is 53% Changes causes o' death SSc over years
and 35% in patients mth
dcSSc and lcSSc,
Il-D in SSc affects survival
median survival of
patents with SSc-lLD is
5-8 years'
ILO is the leading cause of
SSc-related mortality,
accounting for —35% of
SSc-related deathsJS

9. oco
Early diagnosis of CTD-ILD is important
because irreversible lung function loss may be asymptomatic'
—50% of patients with SSc have ILO when first assessed by HRCT2
At early disease stages, patients may
be asymptomatic Mth regards to their
ILDt• or have symptoms that are non-
Mamtawung a ot suspicion for ILD •s •nportmt;
in a activity leve to ca•npmsate
for worsenina lung function may go unnoticed by
SEh can be
of unerty•g WD.
ooer
sympto•s
in diaposis.
less lot

10. Early treatment implies changing the
current management paradigm for patients with CTD-ILDs
Steps to help facilitate the early treatment of this patient population include:
Mültairetg a hi*' kvel of suspicion of ILD pat•nts with CTD by:
WbO• cham•s in Oity •covtty by patient-reported outcome measures /
EvaluaOng gatmts ••,m txtcrs for ILO vo "Tsa in gatmts SSc.
at tire o'
Monitoring ag patonts woo develop ILO 'or disease progression. initatirv or esc*ting treatment at
first of progressim•'
In pat±nts with SSc-ILD. hitiatmg treatnmt based the presence risk factors for progression'

11. 000
Corticosteroids have shown evidence
of benefit in non-fibrotic HP but not in fibrotic HP
FW paOents n•04ibtoOc HP in
Of (••67)

12. 000
Rationale for trials of Nintedanib in SSc-lLD
and progressive fibrosing ILD
Previous lack
of approved
treatrnents
Cornmona'tjes
with IPF in
pathways and
Osease
Estabkshed
efficacy
safety •n IPE'.2
predimcal
data12
Nintedar• invacts futdamental processes
of malmonary fibross relevant
The ntifibrotic activity of nintedmi is
independ«tt of initial disease trigger
pocess•s
SSc-lLD ed progressive RD

13. Nintedanib is approved for the treatment
of SSc-lLD1* based on the results of the SENSCIS@ tria13
Niotedanib slowed lung function decline in patients with SSc.ILD'
Of NC Change from baseline in FVC (mL) over 52 weeks•
Difference: 41.0 mL/yr
(95% O: 2.9.79.0): P•o.04
elativ reducti • 44

14. iöR4 000
Nintedanib is approved for the treatment
of SSc-ILD1* based on the results of the SENSCIS@ tria13
Nintedanib slowed lung function deelioe in patients with SSc•lLDJ
Change from baseline in FVC (mL) over 52 weeks•
(pnmyy
0
Difference: 41.0 mL/yr
(95% C': 2.9.79.0).
elativ reducti • 44

15. 000
The SENSCIS@ efficacy results are considered clinically meaningful...
slowed ILO progression
•n rmg• c' patwnts we SSc-ltDt
iiii}
• Patents with dcSSc (51.9%) or lcSSc (48.1%)
i"
• Patients with (48.4%) or without (51.6%)
@rEornitant mycq:henciate at baseline
These results are
generaltable to
climcal practice

16. 000
Smaller declines in lung function in
SENSCIS@ are associated with less worsening of QOL
Prevention of deterioration of lung function may prevent worsening of QoL
Change in SGRQ scoo at 52 by change in FVC %
resub •ere to•rø
ttv t
in
may prevent •vseüg OOL

17. 000
Comparison of the criteria used to define
progressive fibrosing ILD : (INBUILD@) and PPF (ATS Guideline)
ATS 2022
OOty PPF
Meetjnc 21 measure
progressi«
24 bet"
Of dig•g
managerr«t:
— *solute in
• e•idenc• of
t. trx%n and tranchkakctws
2, •4th tr•cOon
regr*orv
Ueti•.g My
24
mco.

18. 000
Estimated 13-40% of patients with different
types of ILDs develop a chronic progressive fibrotic phenotype
Percentage of patients who develop a chronic progressive fibrotic phenotype•

19. The INBUILD@ trial :
Autoimmune-ILDs is one of the largest populations in INBUILD@
Nintedanib (n:332) Placebo (n-331)
24 7
26 6
AJtoimmune

20. Nintedanib consistently slowed FVC decline in patients with CTD-lLDs in the
INBUILD@ trial, regardless of underlying diagnosis
All With in Rau net s2
58%

21. INBUILD@ : Nintedanib reduced risk of time to first acute exacerbation of ILD
or death over whole trial by 33% in overall population
ratio• 0.67
(95* a-. 0.4.0.98)

22. 000
INBUILD@ : Nintedanib improved symptoms L-PF (Living With
Pulmonary Fibrosis) questionnaire scores
04

23. Conclusion
• ILO is the leading cuse of mortality an affects survival rate in with SSc-ILD Dd other CTD-lLDs.
• Early diagnosis md therapy of SSc-lLD and Oth« CTD-ILDS can prevent further irreversible
lung function impairment. deterioration of QoL. and may ultimately prolong
• Immunosupv•ssants and antifibrotics target distinct mechanisms in the pathophysZIogy of CTO-lLDs; both
treatrrmt classes play a role in the effective managemnt of patients With SSc-lLD md other CID-ILDs
• Nintedanib is a multitargeted TKI with antifibrotic and anti-inflammatory properties that inhibits key fibrotic
pathways leading to pulmonary fibrosis. wtuch SSc-lLO and chronic fibrosing ILO with a
progressive phenotype (includes CID-ILO with a progressive phenotype)
• Consistently Nintedanib significant efficacy benefits have Etoss muttole
patients mth SSc•ILD (SENSCIS') and observed in INBUILO• for patients mth ILDs mth a chronic
prowessive phenotype