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Pirfenidone experience in mild-to-moderate Idiopathic Pulmonary Fibrosis in a General Hospital
(percentage of predicted) at 6-12 months, desaturation
during (Six Minute Walk Test) 6MWT=88% and extension
of the fibrosis in HRCT (High Resolution Computed
Tomography) were associated with worst prognosis (6).
The therapeutic approach aims to preserve lung
function and reduce the inflammatory component of the
disease. Pirfenidone is an antifibrotic agent that inhibits
the transforming growth factor beta (TGB-b), increasing
the synthesis of collagen, decreasing extracellular matrix
and blocking the proliferation of fibroblasts. It is indicated
for the treatment of mild-moderate IPF (FVC> 50%,
DLCO> 35%). The clinical efficacy of pirfenidone has
been studied in three studies in Phase 3, multicenter,
randomized, double-blind, placebo-controlled patients with
IPF, which has shown a 30% improvement versus placebo
in the FVC (8,9).
2. OBJECTIVE
To describe the main clinical outcome in patients mild-
moderate IPF treated with pirfenidona after a year of
monitoring follow-up the therapeutic protocol stablished in
the hospital.
3. METHOD
When pirfenidone was available for clinical practice in
our hospital, Pneumolgy and Pharmacy departments
reached an agreement about the use of pirfenidone,
demarcating clinical conditions that must be met to start
the treatment. The pirfenidone-use criteria for a new
patient was: diagnosis of mild-moderate IPF (forced Vital
Capacity (FVC) >50% and diffusion of Carbon Dioxide
(DLCO) >35%, age<80 years, charlson index<3
(excluding age), absence of severe renal impairment
(ClCr<30 ml/min), absence of acute liver failure, advanced
fibrosis, cirrhosis or hepatocellular carcinoma, no
hypersensitivity to pirfenidone and no significant drug
interactions (no administered with fluvoxamine, grapefruit
juice or other inhibitors of cytP4501A2 and rifampicin,
snuff or other inducers cytP4501A2). Patients starting
treatment between January and March 2014 were chosen.
A monitoring program was established during the first year
of treatment which included lung function and biochemical
study at months 1, 4, 8 and 12 from the beginning. The
main clinical outcome was evaluated by the response; at
month 12 was considered as positive when FVC and
DLCO were increased from baseline, and was considered
stable when FVC and/or DLCO do not decrease more than
@Real Academia Nacional de Farmacia. Spain
10% and 15% from the baseline respectively. Withdrawal
criteria were established when FVC and/or DLCO were
reduced more than 10% and 15% respectively (All
reductions were considered absolute from the baseline
value). All patients were treated with an oral pirfenidone
increasing-dose schedule: induction dose of 267 mg (1
pill) each 8 hours during the first week, 534 mg (2 pill)
each 8 hours during second week, and maintenance dose of
801 mg (3 pills) each 8 hours from the third week if
adequate tolerance.
From electronic clinical records, were obtained:
demographic data, FVC, DLCO, date of start of treatment,
dosage and adverse effects experienced. From pharmacy
record were obtained dispensed pills. Adherence was
computed as percentage of dispensed pills with respect to
theoretical total pills must be taken during follow up
period. Cost of pirfenidone was calculated as acquisition
hospital costs at December 31, 2014.
4. RESULTS
Ten patients (9 males) with mild IPF met the criteria
for starting treatment. The mean age was 69.5±5.0 years
and the average time from diagnosis to starting treatment
with pirfenidone was 2.7±1.8 years (range 1-7 years).
Seven patients received N-acetylcysteine as a
pretreatment. Until the time of marketing, all treatments
initiated were authorized by the Agencia Española del
Medicamento (AGEMED) and processed as “foreign
drugs”. Eight of the ten patients continued on treatment
until month 12. One patient died a month after starting
treatment for not related lung pathology reasons. One
patient discontinued pirfenidona in the eleventh month due
to adverse effect (severe tremor). According with
established criteria, 7 patients presented at month twelve a
positive response, and only one patient did not achieve
therapeutic targets established (improvement or stability)
and treatment was changed to nintedanib at 12th month
from the beginning. Mean baseline of FVC and DLCO
were 85.3±15.4% and 55.6±16.7% respectively. Figure 1
compares our population with the results published in the
clinical trials (8-9); at week 52 (12 months), our patients
had a mean change in FVC (%) of -2.4±6.9% versus -5.2%
reported on clinical trials in the pirfenidone group (-8.3%
with placebo). Table 1 shows FVC and DLCO results at
12th month and response for each patient.
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