Biologic treatment of inflammatory bowel disease in Poland, 2012–2020: nationwide data

Abstract

Introduction:
The frequency of biologic drug treatment for Polish patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) has been partly assessed.

Objectives:
We aim to analyze the use of biologic treatments among Polish patients suffering from IBDs.

Patients and methods:
We used administrative data collected by the National Health Fund (NFZ), Poland's sole public payer. IBD cases were defined as cases with ≥2 records assigned code K50 or K51 and either ≥2 reimbursed prescriptions for IBD drugs or intestinal surgery preceding the record. We identified IBD patients receiving biologic treatments reimbursed by the NFZ in the years 2012-2020. We assessed the percentages of patients receiving biologic treatments in terms of disease type, gender, age group, and place of residence.

Results:
While 6.8% of Poland's CD patients received biologic treatment in 2012, that figure reached 7.9% by 2020. Biologic treatments were given to 0.4% of UC patients in 2014, compared to 1.6% in 2020. Among patients with both CD and UC, significantly fewer women received biologic therapy than men. The highest percentages of patients receiving biologic treatment for CD and UC were observed in the 10-19 age group, while adults over 70 had the lowest percentage.

Conclusions:
We show a growing use of biologic agents in the treatment of IBD in Poland. Women receive biologic treatment for IBD significantly less frequently than men. The pediatric population features the highest proportion of patients receiving such treatment.

Full text

ORIGINAL ARTICLE Biologic treatment of inflammatory bowel disease in Poland 1
aseries of ileitis cases later classified as CD, long
before thefirst detailed description (1932) of a
patients’ series by BB Crohn and his collabora‑
tors.
1-3
eetiology of both diseases remains un‑
clear, though thesuspected contributing factors
include genetic predispositions, changes in im‑
mune system functioning, and environmental
factors.
4-6
Both diseases are chronic in nature but
with periods of relapse alternating with remis‑
sions; and both tend to develop complications,
including some extraintestinal manifestations.
eprevalence of IBD is increasing steadily
across theworld. According to eGlobal Burden
of Diseases, Injuries and Risk Factors Study,7 there
INTRODUCTION Disclaimer: For thepurpose
of this work, theauthors use theterm “biolog‑
ic drugs” to denote any of theinnovative drugs
used in thetreatment of inflammatory bowel dis‑
ease (IBD), including infliximab, adalimumab, ve‑
dolizumab, ustekinumab, and tofacitinib. Strict‑
ly speaking, tofacitinib is not abiologic drug but
treating it as one fits best with thegovernmental
therapeutic programs being pursued in Poland.
Crohn disease (CD) and ulcerative colitis (UC)
are brought together under thegeneral heading
of IBD. While thefirst case of UC was described in
1859 by Sir Samuel Wilks, it was a Polish surgeon
Antoni Leśniowski who in 1903 first reported
ORIGINAL ARTICLE
Biologic treatment of inflammatory bowel
disease in Poland, 2012–2020: nationwide data
PiotrKucha
1*
, EdytaZagórowicz
1,2*
, DorotaWalkiewicz
3
, JakubPerwieniec
3
,
MichałMaluchnik
3,4
, PaulinaWieszczy
2,5
, JarosławReguła
1,2
1 Department of Oncological Gastroenterology, Maria Sklodowska ‑Curie National Research Institute of Oncology, Warsaw, Poland
2 Department of Gastroenterology, Hepatology, and Clinical Oncology, Center of Postgraduate Medical Education, Warsaw, Poland
3 Department of Analyses and Strategies, Ministry of Health in Poland, Warsaw, Poland
4 Department of Adult Neurology, Medical University of Gdansk and University Clinical Center, Gdańsk, Poland
5 Clinical Effectiveness Research Group, Institute of Health and Society, Oslo University, Oslo, Norway
Correspondence to:
Piotr Kucha, MD, Department
of Oncological Gastroenterology,
Maria Sklodowska‑Curie National
Research Institute of Oncology,
ul. Roentgena 5, 02‑871 Warszawa,
Poland, phone: +48 225 46 23 28,
email: piotr.kucha@gmail.com
Received: March 28, 2022.
Revision accepted: June 27, 2022.
Published online: July 4, 2022.
Pol Arch Intern Med. 2022;
132 (7‑8): 16287
doi:10.20452/pamw.16287
Copyright by the Author(s), 2022
* PK and EZ contributed equally to
this work.
KEY WORDS
biologic treatment,
inflammatory bowel
disease, population
data
ABSTRACT
INTRODUCTION The frequency of biologic drug treatment for Polish patients diagnosed with ulcerative
colitis (UC) or Crohn disease (CD) has been insufficiently studied.
OBJECTIVES We aimed to analyze the use of biologic treatments among Polish patients suffering from
inflammatory bowel diseases (IBDs).
PATIENTS AND METHODS
We used administrative data collected by the National Health Fund (Narodowy
Fundusz Zdrowia [NFZ]), Poland’s sole public health care payer. IBD cases were defined as cases with
at least 2 records assigned code K50 or K51 according to the International Statistical Classification of
Diseases and Related Health Problems, Tenth Revision (ICD ‑10) and either at least 2 reimbursed pre‑
scriptions for IBD drugs or intestinal surgery preceding the record. We identified IBD patients receiving
biologic treatments reimbursed by the NFZ in the years 2012–2020. We assessed the percentages of
patients receiving biologic treatments in terms of disease type, sex, age group, and place of residence.
RESULTS
While 6.8% of Polish CD patients received biologic treatment in 2012, that figure reached
7.9% by 2020. Biologic treatments were given to 0.4% of UC patients in 2014, and 1.6% in 2020. Among
patients with both CD and UC, significantly fewer women received biologic therapy than men. The highest
percentages of patients receiving biologic treatment for CD and UC were found in the 10–19 age group,
while patients over 70 were the adults most rarely treated with biologic drugs.
CONCLUSIONS We showed a growing use of biologic agents in the treatment of IBD in Poland. Women
receive biologic treatment for IBD significantly less frequently than men. The pediatric population features
the highest proportion of patients receiving such treatment.
EDITORIAL
by Myrelid and
Eberhardson

POLISH ARCHIVES OF INTERNAL MEDICINE
2022; 132 (7-8)
2
Activity Index (CDAI) scale, or over 50 points
on thePediatrics Crohn Disease Activity Index
(PCDAI) scale and aprevious failure of aconven‑
tional therapy, for example, glucocorticoids or im‑
munosuppressive drugs. In thecase of ustekinum‑
ab, anadditional condition is theexclusion of
anti ‑tumor necrosis factor (TNF) as afirst ‑line
biologic medicine, due to its proven prior fail‑
ure. In thepresence of aperianal fistula, inflix‑
imab or adalimumab may be used irrespective of
theCDAI or PCDAI score.13
ecurrent therapeutic B.55 program “e
treatment of patients with ulcerative colitis” pro‑
vides thetreatment for patients aged 6 and over
with infliximab, as well as with vedolizumab, to‑
facitinib, or ustekinumab for patients aged 18 and
over. ecriteria to be met by patients in this con‑
text are: amoderate to severe flare of thedisease
defined as 6 or more points on theMayo scale
for adults, and 65 or more points on thePediat‑
ric Ulcerative Colitis Activity Index scale for pa‑
tients aged 6–18, including aprevious failure of
theconventional therapy, or counterindications
where its use is concerned, with simultaneous
counterindications as regards theadministra‑
tion of cyclosporine.14
Until 2022, thetreatments available in both
therapeutic programs were time ‑limited, that is,
could be administered for 12 to 24 months. In
their latest versions (applicable from 2022 and be‑
yond), thetime limits have ceased to be imposed.
eanalysis of such NFZ ‑reimbursed usage of
biologic treatment among Polish patients with
the2 types of IBD represented both theaim and
thesubject matter of theresearch detailed in this
paper.
PATIENTS AND METHODS Data source
Our anal‑
ysis centered on administrative health care–re‑
lated claims in Poland, collected in thedatabases
of theNFZ, thesole entire state health care pay‑
er. We searched therecords for health services
taking theform of individual claims reported to
theNFZ by theservice providers. einitial as‑
sessment concerned theprevalence of IBD in Po‑
land in theyears 2012–2020, with reference to
theprevalent and incident cases in theNFZ da‑
tabase assigned aK50 or K51 code according to
theInternational Statistical Classification of Dis-
eases and Related Health Problems, Tenth Revi-
sion (ICD ‑10).8 Due to alack of electronic data,
there was no possibility of assessing thepreva‑
lence of IBD for theyears 2008–2011, aperiod in
which theCD therapeutic program was already
active. In thenext step, we calculated therates
of thetherapeutic program treatment in CD and
UC patients with reference to age, sex, and place
of residence. We further looked for anassocia‑
tion between theuse of biologic drugs in dif‑
ferent regions of Poland (voivodeships), as set
against thenumber of gastroenterologists prac‑
ticing in each region. elatter data for individ‑
ual years were obtained from thePolish Cham‑
ber of Physicians and Dentists.
were 6.8 million people living with IBD in2017. In
2020, Poland reported 23 574 patients diagnosed
with CD, as well as 73 235 with UC,8 out of ana‑
tional population of some 38 million inhabitants.
Given thelack of clarity as to thecause(s)
of IBD, there is no causative treatment. Rath‑
er, themanagement of IBD includes theuse of
5 ‑aminosalicylates, budesonide, systemic ste‑
roids, immunosuppressive agents (azathioprine,
6 ‑mercaptopurine), and thenewest therapeutic
innovations: biologic drugs and small ‑molecule
immunosuppressive drugs. Two treatment ap‑
proaches have been implemented into clinical
practice: a“step ‑up” one, whereby theintroduc‑
tion of biologic drugs follows afailure of acon‑
ventional therapy, and a“top ‑down” approach in
which biologic drugs represent afirst‑line thera‑
py. So far there has been no strong evidence fa‑
voring one over another,9-12 however, a majority
of gastroenterological associations recommend
the“step ‑up” strategy as astandard approach
in moderate to severe disease course, limiting
theuse of the“top ‑down” one to patients with
poor prognosis on thedisease onset.
Today, in theEuropean Union, and so also in
Poland, there are 5 innovative drugs registered
for use in IBD treatment: infliximab, adalimum‑
ab, vedolizumab, ustekinumab, and tofacitinib.
In Poland, due to thehigh costs of treatment
with innovative drugs, theabovementioned med‑
ications are fully reimbursed by theNational
Health Fund (Narodowy Fundusz Zdrowia [NFZ])
through so ‑called therapeutic programs approved
by theMinistry of Health. etherapeutic pro‑
gram for CD (B.32)13 was established in Novem‑
ber 2007; its counterpart for UC (B.55)
14
was es‑
tablished in October2013. Both have undergone
many changes, most significantly, extensions of
maximum treatment duration and introduction
of new drugs.
ecurrent B.32 therapeutic program “e
treatment of patients with Crohn disease” makes
infliximab or adalimumab available for use in pa‑
tients aged 6 years and above, while vedolizumab
or ustekinumab can be used in those of atleast
18 years of age. Criteria to be met by thepatients
are: asevere flare of thedisease defined by ascore
of more than 300 points on theCrohn Disease
WHAT’S NEW?
To the best of our knowledge, this article is the first to describe the popula‑
tion of Polish patients suffering from inflammatory bowel diseases (IBDs) and
treated with innovative biologic drugs, which are the best treatment options
known for patients with a moderate to severe disease course. Using admin‑
istrative data, we estimated and discussed significant differences in the use
of biologic drugs across different regions of Poland. We also showed a higher
treatment rate for men than for women, as well as a high and rising rate for
the youngest population. Access to modern therapies is crucial for improving
the quality of life for the substantially growing population of IBD patients. We
believe our work will be a helpful reference for evaluating the current situation
of those patients and for predicting future demands.

ORIGINAL ARTICLE Biologic treatment of inflammatory bowel disease in Poland 3
outside that voivodeship and, 2) the number of
patients residing in a given voivodeship treated
in another one. All these migration rates were
calculated for 2020.
Statistical analysis
eprescription rates for
biologic therapies for CD in Poland in agiven
year between 2012 and 2020 were calculated as
thenumber of patients registered in thethera‑
peutic program for CD, as divided by 100 preva‑
lent CD cases. Ananalogous process was run for
UC. However, as biologic therapies for UC had
not been reimbursed before 2014, we calculat‑
ed therates for the2014–2020 period only. Dif‑
ferences in rates for women and men were com‑
pared using theχ
2
test, while voivodeship ‑based
relationships between thenumber of gastroen‑
terologists and therates of patients participat‑
ing in biologic therapy were assessed by calcu‑
lating thePearson correlation coefficients using
R statistical software (version 3.6.2) (R Founda‑
tion for Statistical Computing, Vienna, Austria)
with the“data.table” package (version 1.12.8).
All the tests were 2 ‑sided and significance level
was set ata P value of 0.05.
Ethical Committee estudy representing theba‑
sis for this paper gained approval from theBio‑
ethical Committee of theMaria Sklodowska‑
‑Curie National Research Institute of Oncolo‑
gy (73/2021).
RESULT S Crohn disease eofficial number of
CD patients in Poland rose from 11 107 in 2012
to 23 574 in2020. erates of biologic drug use
among these patients in theyears 2012–2020 are
presented in
TABLE 1
. As many as 751 patients with
CD received biologic treatment in 2012, consti‑
tuting 6.8% of their total number (751/11 107).
enumber of such patients in 2020 was 1863,
representing 7.9% of thetotal number. us, even
though theabsolute numbers of CD patients re‑
ceiving biologic drugs in theanalyzed period dou‑
bled, theproportion of prevalent CD patients
treated with biologic drugs increased only slight‑
ly (TABLE 1).
For most of theanalyzed years, there was asig‑
nificant difference in thefrequency of using bi‑
ologic drugs in men and women. In 2012, 6.4%
of women diagnosed with CD were registered in
thetherapeutic program, as compared with 7.2%
of men (
TABLE 2
). In 2020, thedifference was more
pronounced, with respective rates of 6.7% and
9.0% (P<0.001).
Over theanalyzed period as awhole, thegroup
of patients with CD showing thehighest frequen‑
cy of treatment with biologic drugs were those
aged 10–19 years. Furthermore, it was in this
group that themost marked increase in theshare
of patients receiving biologic treatment was re‑
corded (from 11.8% in 2012 to 21.7% in 2020)
(FIGURE 1; Supplementary material, Table S4).
enumber of hospitals offering biologic treat‑
ment for CD increased from 53 in 2012 to 62
Biologic drug therapies for Crohn disease and ulcer-
ative colitis
Services associated with thebiologic
treatment of CD or UC were identified in theNFZ
service database with relation to specific products
covered by theNFZ contracts (Supplementary ma‑
terial, Table S1). Each patient receiving atleast 1
service over the2012–2020 period was identified
and assigned to aspecific voivodeship in line with
thelocation of thehospital involved and not their
place of residence. epatients treated in more
than 1 voivodeship in agiven year were assigned
to each voivodeship involved.
Prevalence of Crohn disease and ulcerative colitis As
abasis for calculating thepercentage of patients
receiving thebiologic drugs for CD or UC, we used
therespective prevalence for these diseases, as
estimated previously.
8
epatients were select
‑
ed based on thefollowing criteria: 1) atleast 2
services in ahospital, or anoutpatient specialist
clinic, reported with theK50 or K51 ICD ‑10 code,
and either 2) atleast 2 prescriptions filled out for
IBD drugs (as listed in Supplementary material,
Table S2) with aninterval of atleast 2 months, or
3) anepisode of intestinal surgery assigned 1 of
thedefined International Classification of Diseas-
es, Ninth Revision codes (Supplementary materi‑
al, Table S3), prior to atleast 1 service reported
with K50 or K51 ICD ‑10 codes.
enext step classified thepatients as suf
‑
fering from either CD or UC, on thebasis of
theICD ‑10 code reported for thelast service
received, so that each patient was assigned to
thegroup with CD, UC, or both of these diagnoses.
Migration analysis
To assess theuse of thebiolog‑
ic drugs in individual voivodeships and thescale of
patient migration, we calculated thepercentage of
patients who could be regarded as external to each
of the16 voivodeships in Poland. We also calcu‑
lated thepercentage of residing patients treated
in other voivodeships and themigration balance,
defined as thedifference between 1) the number
of patients treated in a given voivodeship residing
TABLE 1 Percentage of Crohn disease patients treated under B.32 therapeutic
program in Poland in the years 2012–2020
Year Number of CD
patients treated with
biologic drugs
Total number of CD
patients
Rate of use of
biologic drugs per
100 cases
2012 751 11 107 6.8
2013 863 13 022 6.6
2014 1084 14 953 7.2
2015 1239 16 784 7.4
2016 1312 18 477 7.1
2017 1454 20 125 7.2
2018 1663 21 712 7.7
2019 1823 23 058 7.9
2020 1863 23 574 7.9
Abbreviations: CD, Crohn disease

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4
of their voivodeship of residence, atfrequency
up to 88.6%. is means that, roughly speaking,
only 1 in 10 CD patients from Lubuskie voivode‑
ship received biologic treatment close to their
place of residence.
Ulcerative colitis
enumber of UC patients in
Poland increased from 49 758 in 2014 to 73 235
in2020. erates of biologic drugs usage among
these patients in theyears 2014–2020 are pre‑
sented in TABLE 3. ere were 207 UC patients
treated with biologic drugs in 2014, which was
just 0.4% of thetotal number (207/49 758).
In 2020, these numbers rose to 1174 and 1.6%
(1174/73 235), respectively; both absolute and
relative numbers of UC patients on biolog‑
ic drugs were markedly higher than in 2014
(TABLE 3).
As with CD, we witnessed asignificant differ‑
ence in theuse of these drugs between men and
in2020. In 2020, thehighest number of such
centers was 10 noted for Mazowieckie voivode‑
ship, whereas both Opolskie and Świętokrzyskie
voivodeships had only 1 such center. FIGURE 2 and
Supplementary material, Table S5 present shares
of patients with CD receiving biologic drugs in
2020 per voivodeship. Substantial differences are
to be noted. In Mazowieckie voivodeship (that in‑
cludes Warsaw, thecapital of Poland), 13.8% of all
patients with CD received treatment with biologic
drugs—a sharp contrast with Lubuskie voivode‑
ship, for which therate was as low as 1.2%. It fur‑
ther emerged that Mazowieckie was theregion of
Poland treating thehighest percentage of patients
from other voivodeships. epatients treated in
Mazowieckie but residing in other voivodeships
accounted for 34.9% of all patients treated with
biologic drugs in this voivodeship. Conversely,
Lubuskie voivodeship had thehighest percentage
of patients receiving biologic treatment outside
TABLE 2 Treatment rates for men and women with Crohn disease under B.32 therapeutic program in Poland in the years 2012–2020
Year Women with
CD under B.32
program
Men with CD
under B.32
program
Total number of
women with CD
Total number of
men with CD
Percentage of
women under
B.32 program
Percentage of
men under B.32
program
P value
2012 363 388 5683 5424 6.4 7.2 0.11
2013 406 457 6638 6384 6.1 7.2 0.02
2014 489 595 7562 7391 6.5 8.1 <0.001
2015 557 682 8505 8279 6.5 8.2 <0.001
2016 563 749 9309 9168 6 8.2 <0.001
2017 624 830 10 100 10 025 6.2 8.3 <0.001
2018 716 947 10 876 10 836 6.6 8.7 <0.001
2019 777 1046 11 529 11 529 6.7 9.1 <0.001
2020 790 1073 11 713 11 861 6.7 9 <0.001
Abbreviations: see TABLE 1
FIGURE 1 Percentage
of patients with Crohn
disease treated under
B.32 therapeutic program
in the years 2012–2020,
by age group
0
5
10
15
20
25
2012 2013 2014 2015 2016 2017 2018 2019 2020
%
Year
<10 y
10–19 y
20–29 y
30–39 y
40–49 y
50–59 y
60–69 y
≥70 y

ORIGINAL ARTICLE Biologic treatment of inflammatory bowel disease in Poland 5
In theyears 2014–2016, thehighest share of
UC patients receiving innovative drugs were those
in their twenties (0.9%). By 2017, however, that
lead position had been taken by thepatients aged
10–19 (
FIGURE 3
; Supplementary material, Table S6).
women. In 2014, therate for patients diagnosed
with UC was 0.3% for women and 0.5% for men.
By 2020, thedifference was even greater, with
rates for women and men reaching 1.4% and 1.8%,
respectively (P<0.001) (TABLE 4).
TABLE 4 Treatment rates for men and women with ulcerative colitis under B.55 therapeutic program in Poland in
the years 2014–2020a
Year Women Men Number of
women
with UC
Number of
men with UC
Percentage of
affected
women
treated under
B.55 program
Percentage
of affected
men treated
under B.55
program
P value
2014 82 125 24 607 25 151 0.3 0.5 0.005
2015 124 174 27 182 27 823 0.5 0.6 0.007
2016 99 152 29 500 30 424 0.3 0.5 0.002
2017 166 241 31 730 32 738 0.5 0.7 0.001
2018 287 405 33 658 34 888 0.9 1.2 <0.001
2019 443 578 35 338 36 742 1.3 1.6 <0.001
2020 509 665 35 964 37 271 1.4 1.8 <0.001
a Therapeutic program B.55 was initiated in 2014
Abbreviations: see TABLE 2
TABLE 3 Percentages of patients with ulcerative colitis treated under B.55 therapeutic program in Poland in
the years 2014–2020a
Year Number of UC patients
treated with biologic drugs
Total number of UC patients Rate of use of biologic drugs per
100 cases
2014 207 49 758 0.4
2015 298 55 005 0.5
2016 251 59 924 0.4
2017 407 64 468 0.6
2018 692 68 546 1
2019 1021 72 080 1.4
2020 1174 73 235 1.6
a The therapeutic program B.55 commenced in 2014
Abbreviations: UC, ulcerative colitis
FIGURE 2 Percentage of patients with Crohn disease treated under B.32 therapeutic program in 2020, by Polish
voivodeships
5.1
1010
7.4
1.2
7.87.8
6.46.4
13.8
3.83.8
11.9
8.4
8.2
55
4.44.4
3.33.3
9
4.44.4
1.2–2.3
2.3–5.8
5.8–8.0
8.0–11.0
11.0–13.8
%

POLISH ARCHIVES OF INTERNAL MEDICINE
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region’s absolute figure of just 5 patients with UC
undergoing biologic treatments. However, as with
CD, Lubuskie voivodeship emerged as thePolish
region from which thehighest proportion (93.1%)
of UC patients sought treatment in avoivodeship
other than their own.
Relations between the number of gastroenterologists
in a voivodeship and the use of biologic drugs
Dur‑
ing the2012–2020 period, thenumber of certi‑
fied gastroenterologists in Poland increased from
713 to1136. Two of theregions boasting thehigh‑
est number of gastroenterologists per inhabit‑
ant were Mazowieckie and Podlaskie voivode‑
ships (each with 4.2/100 000 in 2020). is ra‑
tio was thelowest in Świętokrzyskie voivode‑
ship (1.6/100 000 in 2020). e2020 ratio of
thenumber of gastroenterologists per 100 IBD
patients proved to be thehighest in Mazowieckie
voivodeship (1.7/100), and thelowest in Lubuskie,
Wielkopolskie, and Świętokrzyskie voivodships
(0.7/100) (Supplementary material, Table S8).
However, no significant correlation was noted
between thenumber of gastroenterologists and
thenumber of patients receiving biologic treat‑
ment in any voivodeship (P = 0.166).
DISCUSSION
eanalysis detailed here drew on
Poland‑wide data on theusage of biologic drugs
to treat IBD patients, with costs as reimbursed
by theNFZ. It showed agrowing use of biolog‑
ic drugs over theyears 2012–2020, in terms of
both absolute numbers of treated patients and
shares of all patients in Poland diagnosed with
either CD or UC. Treatment rates increased from
6.8% in 2012 to 7.9% in 2020 among CD patients,
and from 0.4% in 2014 to 1.6% in 2020 within
thepopulation of those suffering from, and treat‑
ed for, UC. efactors potentially accounting for
this increase include, primarily, growing clini‑
cians’ confidence in biologics, arising from abet‑
ter understanding of their modes of action, and
secondly, amounting evidence regarding both
enumber of hospitals offering thebiolog‑
ic treatment for UC rose from 31 in 2014 to 52
in2020. In 2020, thehighest number of such
centers was 8 noted for Mazowieckie voivode‑
ship, whereas Opolskie, Świętokrzyskie, and
Warmińsko ‑Mazurskie voivodeships had
only 1 center each. As for CD, we found clear
voivodeship ‑to ‑voivodeship differences in
therates of using biologic treatment (FIGURE 4;
Supplementary material, Table S7). ehighest
percentage of UC patients treated with innova‑
tive drugs in 2020 was 3.1% and 3.0%, noted for
Świętokrzyskie and Mazowieckie voivodeships, re‑
spectively. ecorresponding value for both Lu‑
buskie and Warmińsko ‑Mazurskie voivodeships
was just 0.2%.
ehighest rate for patients with UC receiving
treatment with biologic drugs in avoivodeship
outside of their place of residence was 40% not‑
ed for Warmińsko ‑Mazurskie voivodeship. How‑
ever, this result is perhaps misleading, given this
FIGURE 4 Percentage of patients with ulcerative colitis treated under B.55 therapeutic
program in 2020, by Polish voivodeships
1.1
1.41.4
1.41.4
0.2
2.12.1
0.80.8
33
0.60.6
22
1.9
1.71.7
0.90.9
3.13.1
0.20.2
2.3
1.21.2
0.2–0.4
0.4–1.0
1.0–1.6
1.6–2.7
2.7–3.1
%
FIGURE 3 Percentage
of patients with ulcerative
colitis treated under B.55
therapeutic program in
the years 2014–2020, by
age group
0
1
2
3
4
5
6
7
<10 y
10–19 y
20–29 y
30–39 y
40–49 y
50–59 y
60–69 y
≥70 y
2014 2015 2016 2017 2018 2019 2020
Year
%

ORIGINAL ARTICLE Biologic treatment of inflammatory bowel disease in Poland 7
of biologic drugs in IBD patients of different ages.
ehighest rate of biologics use was found for
thepatients aged 10–19 years, perhaps because
these are theyoungest patients that are more of‑
ten affected by anaggressive course of thedis‑
ease. AHungarian population study19 taking 30
years of practice into consideration established
that small intestine involvement, perianal fistu‑
las, aneed for systemic steroids, and aneed for
surgery induced by thedisease all arise more of‑
ten in pediatric CD patients than in adults, while
all of thefactors referred to are associated with
poor outcome prognoses. Moreover, just as in
our study, Romberg ‑Camps et al
20
demonstrated
that it was within their youngest (under 18 years
old) population of IBD sufferers that thehigh
‑
est cumulative rate of use of biologics (19%) was
to be found.
Our study further showed that men were more
likely than women to be treated with biologic
drugs. Such afinding was in fact made previous‑
ly in amulticenter Polish study on anti ‑TNF use
in therapeutic programs in IBD.
21
eaforemen
‑
tioned Swedish analysis17 also noted asex ‑based
difference in therate of using thebiologics (sig‑
nificant atP = 0.02).
17
However, this phenome‑
non has no obvious explanation, given conflict‑
ing data on sex‑related differences in IBD courses
and complications. ere are nevertheless stud‑
ies showing that male sex is arisk factor when it
comes to IBD taking amore severe course, with
this extending, in thecase of CD, to ahigher fre‑
quency of involvement of theupper gastrointes‑
tinal tract and small intestine. ese circumstanc‑
es may prompt clinicians to make more frequent
use of biologics.20,22,23 According to other studies,
male sex is anindependent risk factor for exten‑
sive abdominal surgery, including intestinal re‑
sections.
24
It is also worth mentioning that, with
‑
in theIBD population, it is men who most often
go on to suffer—often fatally—from cancer of
thelarge bowel.25,26
Another possible explanation for themore
limited usage of biologic drugs among women
might involve discontinuation of treatment due
to its adverse effects. Some studies suggest that
thefemale sex is anindependent risk factor when
it comes to adverse effects of anti ‑TNF drugs.
27
Moreover, in thePolish case, pregnancy was acri‑
terion that straightforwardly excluded thepa‑
tients from thetherapeutic programs. is was
likely afurther reason why women were treated
with biologic drugs for IBD less often than men.
eremaining significant difference dem‑
onstrated for therates of using biologics is
theregionally ‑based one, given that as many
as 27% of all instances of biologic therapy for
Polish CD patients involved receipt of thedrugs
inMazowieckie voivodeship. ecorresponding
figure for patients with UC was 24%. Atthe oth‑
er extreme, thewestern voivodship of Lubuskie
emerged as contributing theleast to overall bi‑
ologic treatment of Polish CD and UC patients.
In 2020, just 0.27% of Polish patients with CD
their effectiveness and safety. Another probable
factor is theintroduction of biosimilar drugs that
lowered thecosts of thetherapy. is was later
accompanied by extensions of maximal periods
of treatment under available treatment programs
that further encouraged thegastroenterologists
to enroll more patients in thehope of achieving
prolonged remission. One more possible reason
for theincreased rate of using thebiologics among
Polish IBD patients may lie in improved access,
with agrowing number of centers offering this
kind of treatment. Finally, thegradual increase in
thenumber of drugs encompassed by therapeutic
programs over thelast 5 years may have allowed
thepatients failing to respond to thefirst ‑line
therapy to re ‑enroll for new treatments.
eobserved increase in theuse of biologics in
Poland resembles thesituation in other countries.
ADanish nationwide study
15
on enrolled patients
diagnosed with IBD over theyears 2003–2016
found theshare of participants treated with bi‑
ologic agents rising from 0% to 16% for CD, and
from 0% to 5% for UC cases. A2010–2016 Nor‑
wegian study
16
reported anincrease in therate
of use of biologic drugs from 17% to 33% for CD
patients, and from 7% to 13% for UC patients.
Furthermore, astudy from Sweden,
17
themost
methodologically similar to ours (and which ana‑
lyzed thepopulation of IBD patients diagnosed in
theyears 1969–2017, and those treated with bio‑
logics in theyears 2005–2017), pointed to thecu‑
mulative rate of use of thedrugs being as high as
14.5% and 6.7% among patients with CD and UC,
respectively. ASwiss study18 noted anincrease
in theuse of biologic drugs among IBD patients
from 5.3% in 2010 to 12.8% in 2014, albeit with
no distinction drawn between CD and UC. Afur‑
ther limitation of thelatter study was its confine‑
ment to patients insured by asingle Swiss pay‑
er, which covered only around 15% of thepopu‑
lation of Switzerland.
While theshare of Polish IBD patients receiving
treatment has been on therise, it remains below
thelevels noted in other countries for which data
have been published. is would mainly seem to
reflect therestrictive rules applied to Polish ther‑
apeutic programs. In particular, theminimum lev‑
el thedisease activity required for thetreatment
to commence is simply too high to allow many
patients with moderate activity to be included,
along with those for whom conventional treat‑
ment has failed and who experience postopera‑
tive relapse. For every patient taken on, there is
anabsolute requirement to establish afailure of
theconventional therapy. is clearly stands in
theway of any early ‑stage introduction of thebi‑
ologic treatment, despite thefact that thebio‑
logic therapy is proven to be themost effective.
Moreover, the2 Polish programs were previous‑
ly run under time limits, requiring withdrawal
after 12 or 24 months, even if thetreatment re‑
mained efficient.
Afurther key observation from our study con‑
cerned significant differences in thedeployment

POLISH ARCHIVES OF INTERNAL MEDICINE
2022; 132 (7-8)
8
SUPPLEMENTARY MATERIAL
Supplementary material is available at www.mp.pl/paim.
ARTICLE INFORMATION
ACKNOWLEDGMENTS None.
FUNDING This work was supported by the European Union via the Euro‑
pean Social Fund and within the framework of the Knowledge ‑Education‑
‑Development Operational Programme (Project entitled, “Maps of Health
Needs – A Database of Systemic and Implementation Analyses”), grant
number POWR.05.02.00 ‑00 ‑0149/15. Language editing was funded by
the Polish Foundation for Gastroenterology.
CONTRIBUTION STATEMENT PK, EZ, and JR initiated the work. PK and
EZ interpreted data and drafted and revised the manuscript. DW and PW
analyzed the data and participated in drafting of the manuscript. JP and
MM participated in the study design and drafting. JR also participated in
the study design, while later being involved in revisions of the manuscript.
All authors have read and accepted the manuscript in its final form, includ‑
ing the authorship list.
CONFLICT OF INTEREST All the authors have provided statements on
financial conflict of interest. DW, JP, MM, and PW declared no such con‑
flict. PK declared support for attendance at meetings from Janssen. EZ de‑
clared support for attendance at meetings or for travel from Takeda and Fer‑
ring, as well as individual honoraria for consultancy or lectures from BMS,
Takeda, Janssen, Ferring, and Fresenius Kabi. JR declared support for atten‑
dance at meetings or travel from Servier and Alfasigma, as well as individ‑
ual honoraria for consultancy or lectures from Alfasigma, Servier, Janssen,
Takeda, Amgen, and Ipsen.
OPEN ACCESS This is an Open Access article distributed under the terms
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Inter‑
national License (CC BY ‑NC ‑SA 4.0), allowing third parties to copy and re‑
distribute the material in any medium or format and to remix, transform, and
build upon the material, provided the original work is properly cited, distrib‑
uted under the same license, and used for noncommercial purposes only. For
commercial use, please contact the journal office at pamw@mp.pl.
HOW TO CITE Kucha P, Zagórowicz E , Walkiewicz D, et al. Biologic treat‑
ment of inflammatory bowel disease in Poland, 2012–2020: nationwide
data. Pol Arch Intern Med. 2022; 132: 16287. doi:10.20452/pamw.16287
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treated with biologic drugs were cared for in that
voivodeship. ecorresponding figure for UC was
just 0.34%. ekey reason for this would seem to
involve limited access to specialist gastroenterol‑
ogy care in many patients’ respective regions of
residence. Data from thePolish Chamber of Phy‑
sicians and Dentists reveal that, while Mazow‑
ieckie voivodeship had 226 gastroenterologists
in 2020 (or 1.7 per 100 IBD patients), Lubuskie
voivodship had amere 17 (or 0.7 per 100 IBD pa‑
tients). Nevertheless, it was not possible to estab‑
lish any significant correlation between thenum‑
ber of gastroenterologists in agiven voivodeship
and thenumber of patients treated with biologic
drugs (with P = 0.17).
ese last differences might be partly explained
by migration of IBD patients in search of treat‑
ment, to thehighly ‑specialized centers mainly lo‑
cated in thecapital and atacademic units. While
there were several dozen centers offering biolog‑
ic treatment across thecountry as of 2020 (62
for CD and 52 for UC), the5 most ‑utilized ones
served no fewer than 38.3% of thecountry’s CD
patients and 35.1% of thecountry’s UC patients.
Migration balance was thus definitely positive
in thecase of Mazowieckie voivodeship, with al‑
most 35% of CD patients and nearly 26% of UC
patients receiving biologic treatment there com‑
ing from beyond theregion’s borders. Atthe oth‑
er extreme, in Lubuskie voivodeship, more than
88% of theresident CD patients on biologic drugs
received this treatment in another voivodeship.
In thecase of UC, thefigure was 93.1%.
Several limitations to our study include our
confinement to IBD patients whose treatment
gained NFZ reimbursement. Our analysis exclud‑
ed patients treated as part of clinical trials. We
have no insight on theproportion of IBD patients
given biologic drugs in non ‑NFZ contexts. Afur‑
ther problem related to alack of precise compara‑
bility reflects changing regulations of thethera‑
peutic programs, above all regarding limited du‑
rations and thevariety of drugs available. Equal‑
ly, some IBD patients were enrolled in both of
thetherapeutic programs analyzed (B.32 and
B.55), due to changes in diagnosis (most often
from UC to CD). at confers aslight bias upon
thepercentage of patients treated for thepartic‑
ular diseases. Moreover, theaforementioned un‑
equal geographic access to thetherapeutic pro‑
grams might also have generated aselection bias.
To conclude, our analysis of theuse of biolog‑
ic drugs among Polish IBD patients over thelast
decade confirmed aslow increase, sex ‑based dif‑
ferences, age ‑related differences, and anunequal
geographic distribution of gastroenterological ser‑
vices providing thebiologic therapy in individu‑
al Polish voivodeships. ese results may in part
reflect alimited access to innovative therapies
due to tight reimbursement criteria. We believe
these data are of importance atthe national lev‑
el, especially for those involved in theplanning of
thehealth policy, but also for medical profession‑
als all over theworld who deal with IBD patients.

ORIGINAL ARTICLE Biologic treatment of inflammatory bowel disease in Poland 9
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