nerandomilast Flashcards
(20 cards)
how does nerandomilast work
it is an oral phosphodiesteraase 4B inhibitor
what were the inclusion criteria of fibroneer ipf
40 years old
FVC > 45%
DLCO >25%
IFP = UIP or probable UIP (centrally reviewed) or pathology proven
what were the exclusion criteria of fibroneer ipf
what was the size of fibroneer ipf and how were patients allocated
1177 patients assigned 1:1:1 to placebo, 9 MG BID, or 18 MG bID. Randomization stratified by prior antifibrotic use
what percentage of patients took antifibrotics at baseline in the fibroneer ipf study?
77.7% were taking an antifibrotic
describe the baseline pt characteristics of fibroneer ipf participants
80% male, age 70, 3-4 years since diagnosis, mostly former smokers
average FVC 78, average DLCO 51
compared to inpulsus - slightly older, slightly longer duration of disease, smiilar FVC and DLCO
how was the sample size calculated for fibroneer ipf
inpulsus demonstrated a 110 cc difference between ofev and placebo at 52 weeks.
They powered inpulsus to detect the same difference between nerandomilast and placebo
However, they assumed 70% would be on nintedanib. In that case they assumed a 65cc difference. They blended them to get an overall difference of 74cc. 90% powered with two sided alpha.
what was the primary outcome and result of fibroneer ipf
FVC mean change from baseline at 52 weeks
they found 18 mg did the best at -114, followed by -138 at 9mg, followed by -183 for placebo
the between group difference between placebo and 18 mg was 45 ml
benefit seems to persist whether or not on basleine antifibrotic therapy
- nintedanib between groups was 118 vs 191 for a 73 cc difference
- no therapy between groups was 148 vs 79 for 69 cc difference
describe the adverse events noted in fibroneer ipf
most common was diarrhea, dose related
- 62% if on nintedanib
- 26% if alone
what is the interaction between pirfenidone and nerandomilast
there is a pharmacokinetic interaction where drug levels were decreased by 50%. there was still a trend towards benefit in the subgroup analysis.
what was the size of fibroneer ild and how were patients allocated
1176 patients, international multicenter, 1:1:1 18 v 9 v placebo - same as fibroneer ipf
- stratified by UIP or no, nintedanib or no
what were the inclusion criteria for fibroneer ild
non-IPF ILD with 10% fibrosis on HRCT within 12 months, reviewed centrally
FVC 45
DLCO 25
a relative decline of at least 10% in the percentage of the predicted FVC; a relative decline of at least 5% but less than 10% in the percentage of the predicted FVC with worsened respiratory symptoms, an increased extent of fibrotic changes on imaging, or both; or worsened respiratory symptoms and an increased extent of fibrotic changes on imaging.
nintedanib allowed if stable for 12 weeks
how was immunosuppression allowed in fibroneer ild
Immunosuppressant therapy that had been received at a stable dose for at least 12 weeks was permitted at enrollment, with the following exceptions: cyclophosphamide, tocilizumab, mycophenolate (mycophenolate mofetil or mycophenolate sodium), and rituximab were not permitted at enrollment but could be prescribed after 6 months to manage worsening of systemic disease, and prednisone at a dose of more than 15 mg per day or equivalent was not permitted at enrollment but could be prescribed for acute exacerbation of ILD. Other changes in immunosuppressant therapy were not permitted during the first 6 months of the trial.
how was the sample size for fibroneer ild calculated
in inbuild a difference of 107 cc per year was found between ofev and placebo
this trial estimated 85-90 cc per year for pts on placebo and 55-60 for patients on ofev. They took a weighted average to get 70% off ofev and 30% on ofev to power for a 71 cc benefit.
notable this is the same as fibroneer ipf
how do the baseline characteristics of inbuild and fibroneer ild comapre
fibroneer ild 1100 pts - 66, ~55-60% male, 50% smokers, 70% FVC, 50% DLCO, 43% on nintedanib, 70% UIP
28% CTD ILD, 20% HP, 20% unclassifieable, 20% iNSIP
inbuild 600 pts - 65, ~53% male, 50% former smokers, 62% UIP, FVC 69, DLCO 45%
26% HP, 25% CTD ILD,
what were the results of fibroneer ild
all comers - better with 9 than 18, 84 vs 165 per year difference of 81
consistent on or off ofev
- on: 87 vs 180 for difference of 93
- off: 154 vs 82 difference 71
The lines seem to be parallel after 26 weeks
what about secondary outcomes in fibroneer ild
trend towards benefit for all of: death, ILD exacerbation, or hospitalization. better with 18 vs 9 which is opposite of FVC
how does the benefit of fibroneer ild compare to inbuild?
the placebo group lost 187 cc per year in inbuild as opposed to 165 cc per year in fibroneer. both treatments resulted in a loss of 80cc per year, so technically the benefit of ofev was greater (100 vs 80 cc per year)
in fibroneer ild what is the most common adverse reaction
diarrhea - 27% alone, 50% with nintedanib
