International Journal of Medical Sciences And Clinical Research
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VOLUME
Vol.05 Issue06 2025
PAGE NO.
10-15
10.37547/ijmscr/Volume05Issue06-02
Our Experience with The Use of Interleukin 6 Inhibitor -
Tocilizumab, In the Complex Treatment of Nonspecific
Aortoarteritis
Akmal Abdullayevich Irnazarov
Republican specialized center of surgical angioneurology, Tashkent Medical Academy, Uzbekistan
Abdurasul Abdujalilovich Yulbarisov
Republican specialized center of surgical angioneurology, Tashkent Medical Academy, Uzbekistan
Khojiakbar Kashipovich Alidzhanov
Republican specialized center of surgical angioneurology, Tashkent Medical Academy, Uzbekistan
Saidjon Khomitali ugli Rakhmataliyev
Republican specialized center of surgical angioneurology, Tashkent Medical Academy, Uzbekistan
Received:
12 April 2025;
Accepted:
08 May 2025;
Published:
10 June 2025
Abstract:
The need for further improvement of treatments for Takayasu's arteritis (TA), the progress in
understanding the mechanisms of the disease, and the introduction of biological agents (BA) in rheumatology
practice have created preconditions for developing a new TA pharmacotherapy using BA associated with
interleukin 6 (IL-6) inhibition.
The authors describe their two own cases of tocilizumab (TCZ) use for complicated TA. In one case with a long
history of complicated TA and glucocorticosteroid intolerance, the use of TCZ contributed to the control of disease
activity. In the other case with the onset of TA and focal pulmonary tuberculosis (TB) treated with anti-TB drugs
during TCZ monotherapy for 6 months could control TA and achieve TB cure.
The use of IL-6 inhibitors should be considered as a potentially effective and relatively safe innovative (off-label)
treatment for refractory TA in patients with intolerance or contraindications to standard therapy, which requires
further larger randomized clinical trials.
Keywords:
Nonspecific aortoarteritis ; Takayasu's arteritis; interleukin 6; tocilizumab.
Introduction:
Takayasu arteritis ( TA ) or nonspecific
aortoarteritis is systemic in the group of vasculitis ( TV
) . disease big, big of the veins damage with is
described, usually from the age of 50 small in patients
develops and a medium and his/her main networks
Arteritis, often granulomatous, superior contamination
with is described. [1].
The etiology of TA is unknown, the influence of genetic
factors is more discussed, and TA is considered a typical
HLA class II disease, in contrast to giant cell arteritis
(GCA), another form of large-vessel TB that is
associated with HLA class I. [2-4]. Antibodies have been
shown to be associated with HLA-Bw52 and HLA-B39
[3, 5], and patients with the HLA-B39 allele have been
shown
to
respond
poorly
to
standard
immunosuppressive therapy and require the use of
GABA (genetically engineered biological drugs) [6].
The rarity of TA, the variability of the lesion sites [7],
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and the lack of standard reliable instrumental or
laboratory markers of activity [8] explain the lack of
randomized controlled trials on TA until recently.
According to the results of retrospective observational
studies, standard treatment with glucocorticoids (GCs)
and cytostatics, primarily methotrexate (MT) [9] may
not be sufficient to achieve complete stable remission
of TA. Thus, D. Freitas et al. [10] During treatment with
GCs and MT, the progression of the disease is detected
in 75% of cases with new localization of vascular
damage during instrumental examination. According to
various authors, relapses develop in 22-72% of patients
with TA with a decrease in the dose of GCs [11-13]. In
turn, the complications of GCS therapy can compete
with the complications of the underlying disease. In
addition, the use of GCS in patients with renal artery
disease is limited due to the increased risk of secondary
hypertension.
In patients with clinically hemodynamically significant
circulatory disorders, surgical treatment is used, i.e.,
angioplasty or stenting is used for high-grade arterial
stenosis; in stenosis accompanied by severe periarterial
fibrosis or occlusive stenosis, bypass and other
reconstructive procedures are performed. Surgical
procedures are never performed in the active phase of
TA. However, during routine examinations, the activity
of the disease may not be evident, segmental
inflammation of the blood vessel wall sometimes
proceeds subclinically, and laboratory tests do not
correspond to the activity of inflammation, which can
lead to ineffective surgical treatment. Thus, as reported
by K. Maksimowicz-McKinnon et al. [13], despite the
initial successful results of vascular surgery,
subsequent re-stenosis developed in 78% of cases of
angioplasty
and
in
36%
of
patients
after
bypass/reconstructive intervention. According to the
results of the observations of M. Isobe et al. [14], 3-6
years after bypass surgery, occlusion or restenosis is
observed in 8-31% of patients with TA.
In recent years, the need to further improve the
treatment of TA, advances in understanding the basic
mechanisms of TA pathogenesis, and the introduction
of genetically engineered biological drugs ( GEBDs ) into
rheumatology have created the necessary conditions
for the development of a new direction in recent years.
GEBDs with the help of TA 's pharmacotherapy, first in
turn, is associated with inhibition of interleukin 6 (IL-6).
Treatment of T A potential target for as IL- 6
importance Suffering from TA aorta in patients and
large veins of IL-6 in tissues exactly expression [15, 16]
and IL - 6 and his/her soluble receptors in serum
concentration [16-21], in serum soluble IL-6 receptors
level and TA activity [21 ] . Interestingly is that it is
different from TA as, act
ivity in Г C A his/her soluble not
related to receptors, but to IL-6 was.
Since 2008 [22], tocilizumab (T Ts Z), IgG 1
immunoglobulin lower from class human IL-6 receptor
for recombinant humanized monoclonal antibodies,
soluble and selectively with membrane IL-6 receptors
binds, suppresses classical and trans-signaling IL. 6
receptor pathways 6 individual cases of TA, especially
to standard therapy durable or to him against to the
instructions owner those who were in treatment
successful is used. Recently small Japanese couple
randomized, placebo- controlled, phase III test (RP C T)
first The results are presented in [23]. They are
refractory TA remission save stay for T Ts Z security and
efficiency studied.
METHODS
We are G K C and from cytostatics limited complicated
to use Using T Ts Z in TA according to two own our
observations present We will.
Patient M. From the age of 13, repeated erythema
nodules and arthralgias appearance sick since. from
2017 from up to 39°С fever added, blood pressure (AQB
) 200/100 mm .sim .ust. rose to B soup pain , up to 7
times a day unconscious to leave , to leave of the hand
inactivity was observed . 2017 in September of the year
first pregnancy during inspection on time Doppler to
ultrasound ( ultrasound ) data according to general
sleep artery stenosis is determined up to 70% .
Pregnancy medical for reasons according to stopped .
In December 2019 when checked C - reactive protein (
CRO ) level is 34 mg/l, hypercoagulation signs , selective
in angiography left general sleep artery ( IUA ) up to
70% stenosis, external U A has up to 80% stenosis
approved . TA diagnosis placed of India blood vein
surgery in the department left general UA
alloprosthesis to do increased , surgery from treatment
then situation noticeable to the extent improved , but
left in hand weakness and insomnia preserved left .
2021 January in the month second pregnancy during , 6
weeks for the period . left inner and outside In the UAE
blood of the stream with preservation of the total UA
prosthesis occlusion diagnosis was put of the situation
progressive deterioration, unconsciousness leave,
dizziness, left hand of your fingers movement
weakening, unstable blood pressure 210/100 mm.
raised to Pregnancy during Clexane 40 mg per day was
made. From March 2021 from Republican surgery
angioneurology specialized in the center treatment
started and observed.
36 weeks in September 2021 during pregnancy
cesarean section Successfully cut the road with a dead
end the birth was done. Originally from Russia later
arteriodynia record was made , colored Doppler
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ultrasound to check according to the left inner U of A
stenosis added up to 50% . Belly space aorta and
his/her
on
the
horns
injury
signs
no
.
Methylprednisolone 20 mg per day subjective
tolerance , blood pressure increase ordered with
episodes . One- time from injection then MT 10 mg of
transaminase levels increase because of useless done ,
heart nausea , diarrhea and Azathioprine (AZA) 100 mg
daily was prescribed , treatment was further
complicated by dyspepsia. complicated . Clexane - 60
mg per day . To treatment despite ultrasound during
the inspection left internal U A stenosis increased to
80% and left outside The wall of A thickening added .
20 22 - in March T Ts Z 8 mg/ kg first and second
injections with an interval between 2 weeks , then 4
weeks , the last infusion 20 22 years October in the
month added . T C Z is one with monthly from
treatment then C R O level is 1.7 mg /kg did E ChT - 11
mm/ h , thrombocytes - 321 ×109/l.
20 in November 22 In India to the patient left internal
and on the side outside U A main in blood current
restored in case subclavian-general sleep prosthetics
successful was conducted . From the operation next
early during complications not observed , CRO - 16
mg/l, thrombocytes - 423 × 109 /l, procalcitonin test is
negative .
202 3 - year February in the month planned inspection
at the time : C P O level - 0.9 mg/l, ESR - 14 mm/ h ,
platelets - 420 ×109/l, colored Doppler ultrasound
during the inspection blood vein prosthesis you can see
that the blood flow is good .
TA of far continue which natural course (
immunosuppressive 15 years without therapy ) under
observation to other localization arteries damage non-
transmission , improvement of turgor , treatment with
T C Z during C R O level normalization inflammation
effective evidence of reduction gives .
Second sick woman patient M.,
20 years old , April
2018 month from a respiratory infection then cough ,
in May 2018, the Republican Phthisiology and
pulmonology in the center passed inspection on time
right lung high part of focal tuberculosis determined .
diagnosis placed and treatment with pyrazinamide ,
rifampicin and ethambutol ordered . Soon general
weakness , fever up to 38°C , high on the feet pain ,
headache , fainting once departure is added . Right on
the side blood pressure when checking - 100/70 mm
.sim .ust., left - 70/40 mm .sim .ust. , C R O level - 21.2
mg/l, Doppler ultrasound - general It's A 's. two side by
side stenosis up to 60-85%, subspinal arteries - up to
65-80%. July 2018 from the month Since the Republic is
specialized surgery angioneurology in the center is
being observed . TA diagnosis Joint work with
phthisiologists from consultation then , GK C from of
use sharp limitation and potentially more convenient
due to security profile , 2019 February 8 mg/kg T C Z
was added at 4 -week intervals until the end of the
month , for a total of 3 infusions . Treatment as a result
the rise in div temperature is gone , in the hands of
pain
noticeable
to
the
extent
decrease
,
unconsciousness of leaving absence and C R O level
positive with normalization impact record was done .
From September 2019 from 7 months then T C Z 's last
from infusion then , general weakness , fever up to 38°
C , myalgia , shortness of breath heart rate palpitations
, headache in the form of of health progressive
deterioration . When examined in computed
tomography (CT) , right your lungs high in the future
pleuroapical contracts and local fibrosis had the
appearance , negative Mantoux test , tuberculosis
treatment It will be shown .
Again during examination : C R O - 3 1 , 4 mg/ml, E ChT
- 41 mm/s, platelets - 413 × 109/l, duplex ultrasound
also TA in the inspection development signs (Table 1) of
blood flow in the brachiocephalic arteries trunk ,
internal stenosis with the development of . Right side
view U A, general U A, right subvertebral artery stenosis
development , abdomen aorta of the walls thickening
and his/her main visceral branches without signs of
stenosis . of stenosis increase and new of injuries
appearance with the possibility of of recurrence
diagnosis placed .
TA induction Treatment: 4 -weekly intervals with a total
dose of 8 mg/kg , 2 infusions in total , Clexane 40
mg/day, then in combination with clopidogrel 75
mg/day positive continue with the effect . With
improved stability and mild positive dynamics after 4
months. According to Doppler ultrasound examination
of the brachiocephalic arteries (see Table 1). In May
2020, during outpatient follow-up with diffusion-
weighted magnetic resonance imaging (DWIMS MRI),
evidence of the absence of active inflammation in the
walls of the UA on both sides, the main blood flow in
the brachiocephalic arteries , bilateral subclavian
arteries was obtained. and no changes were observed
in all parts of the thoracic aorta, the abdominal aorta
and its branches.
T Ts Z monotherapy ineffective to the effect regardless
of its efficiency undoubtedly evidence , one from the
side , right the subvertebral artery also changed main
blood of the stream preserved it remains , this and
div
temperature
with
normalization
and
improvement of stability will come Q is dead of pain
disappearance and unconscious of leaving absence , C
R O of decrease and other on the other hand , T Ts Z
infusions since it ended many without delay negative
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
dynamics. of observation e -bite the patient's far in the
region related to living What is T C Z? take throw during
of antibodies activity about of information absence was
T Ts Z therapy in the background GCS and cytostatics
exception did in case TA activity control to do lung
tuberculosis for treatment possibility gave . So so , this
in case therapy general effect positive because
calculation It is possible , but it is not possible not .
DISCUSSION
Presentation done initial information that shows that T
Ts Zni in TA induction including in treatment refractor
on the course effective to be to the potential have Note
that should be refractory TA 's general reception done
definition no : Rule as , they are GKS dose from
decreasing later disease of activity increase or at least
one cytostatic to apply despite of activity continue verb
means [2]. Turkish researchers [3] refractory TA for
criteria offer did : continue doing for treatment despite
angiographic or clinical progression; from 6 months
later of prednisolone dose >7.5mg/day , from
cytostatics to use despite treatment ; TA activity
because of new operation; frequent relapses ( from 3
times a year more ); TA activity because of death .
Treat T Ts Z in TA general efficiency high indicators
about impression (84.6%) each tenth The patient has G
K C. and cytostatics every per second , inclusive
refractor Treatment with TA successful stop fact
confirms . GK S 's dose reduction or take throw
opportunity and T Ts Z monotherapy effectiveness [17,
18, 23] in patients with TA in patients additional
prospects opens , their most of them are young women
. S. Yes and others by to a large study conducted
According to [12], 240 pregnancies were recorded in 96
patients with TA . analysis when done , the disease of
pregnancy to the result negative impact to show , TA
activity , mainly due to arterial hypertension obstetrics
and motherhood complications danger increase record
treated with T C Z in women pregnancy of the results
publication done in the analysis fetus anomalies of
danger increase about no what evidence no and early
birth level (31.2%) overall to the population relatively
increased was determined [12].
To emphasize this It is necessary to treat with T C Z. as
a result of the veins narrowly to stay pathological of the
process several years from the chair later both return
possible . So By Y. Nakaoka and others . [23] and N.
Nishimoto and others . [22] TA situations present They
did it , it took 4-5 years. continue did disease from
activity after using T Ts Z then , narrowed of the veins
to recanalization achieved .
French researchers group by take visited one row In
studies , treatment with T C Z [24] three annual relapse-
free treatments about the information present , which
exceeded the results of standard immunosuppressive
therapy ( 58.7%; p = 0.0025) and amounted to 85.7%
did Twice in remission phase randomized placebo
control underneath tests III ( TPNOS ) [23] Maintenance
with T Ts Z therapy background , from 6 months later
without recitative viability was 50.6% and compared to
the PL group (22.9%). high was , but differences are
statistically significant owner not was (p = 0.0596).
T randomized placebo control underneath results of
trials ( TPNOS ) [23]. discussion when doing , GKS is the
same as accepted from the moon later properties of
reducing the amount in the blood to account to take
necessary , this is in clinical practice does not apply and
T Ts Z treatment mode for monotherapy brings closer .
Send T Ts Z of the subcutaneous route the effect both
discussion to do possible , because initial to research
according to this T Ts Z dose decrease like negative
impact showed [21]. From this except in Japan passed
TPNOS the results discussion in doing , suffering from
TA in patients clinical course of the disease , including
process spread geography and to the nation looking at
changed to stand indifferent leaving will not happen .
Initially in research treatment the results in evaluation
we improvement or remission included general
efficiency seeing We went out because TA activity
assessment methods and in sources report The format
was very diverse . From except , treated with T C Z
Suffering from TA in patients blood vein of the wall
inflammation activity too narrow to the extent
assessment is very difficult . Y. Seco and to others
According to [15], C R O and E CHT degrees to normalize
and treatment with T C Z during TA clinical signs of
activity to disappear regardless , two from the situation
one of them is MR T angiography results blood vein of
inflammation continue verb showed . L. Pulsatelli and
to others According to [21], 10 patients with TA were
treated with T C Z. six infusion ordered ( 9 of them with
refractory course) clinical remission in 70 % of patients
achieved , clinical activity index positive dynamics ,
laboratory markers (E ChT, C R O ) and in 60% of cases ,
it is instrumental methods decreased done .
TA diagnosis put , damage of localization determination
and activity observation instrumental studies for value
excessive assessment difficult , but this methods always
reliable not [8]. Invasive x-ray contrast angiography yet
both TA diagnostics for to be the gold standard
regardless of its disadvantages there is also , for
example , the effect of radiation and contrast material
use necessity and them regularly inspection for using
will not happen .
So so the initial clinical trials collected information ,
own our experience and two stage TPNOS III associated
with IL -6 inhibitors was Innovative induction of TA and
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keeper of treatment It shows the effect and bigger
additional randomized clinical trials explanation
demand does . The present in time of veins in TA
condition about complete information universal
representation that gives method exists absence due to
, individual methods known and additional for the price
Treatment with HAART in the background TA activity
monitoring , clinical data , laboratory signs and
instrumental vision methods , first first , invasive those
who are not every side by side to evaluate to include
need .
CONCLUSIONS
The effect is inhibition of IL-6 to do directed Using
GAYaBP A potentially effective treatment for TA and
relatively safe innovative ( from label except ) method
as seeing discharge need , first in line refractory course,
GK and to cytostatics relatively intransigence if , else
side to GAYaBPs or standard therapy against
instructions existence .
Initially of research collected to the information
according to , treatment with T C Z as a result Suffering
from TA in 85 % of patients , including refractor
remission or improvement observed . I kki side by side
TPNOS III According to the phase effect , 6 months with
T C Z from treatment later relapse-free period to the PL
group than high ( suitable 51 and 23% respectively ),
however differences are statistically significant owner
not (p = 0.0596).
Further clinical studies standardization for Treatment
of TA efficiency assessment methods improvement
necessary , at the same time GAYAPP treatment with in
the background TA activity monitoring , clinical data ,
modern laboratory biomarkers and instrumental
imaging methods , first mainly non -invasive , non-
invasive those who were every side by side to evaluate
to include need .
REFERENCES
Jennette J, Falk R, Bacon P, et al. 2012 revised
International Chapel Hill Consensus Conference
Nomenclature of Vasculitides . Arthritis Rheum.
2013;65(1):1-11.
Carmona FD, Coit P, Saruhan-Direskeneli G, et al;
Spanish GCA Study Group; Italian GCA Study Group;
Turkish Takayasu Study Group; Vasculitis Clinical
Research Consortium. Analysis of the common genetic
component of large-vessel vasculitides through a meta-
Immunochip strategy. Sci Rep. 2019;7:439 -53.
Saruhan-Direskeneli G, Hughes T, Aksu K, et al.
Identification of multiple genetic susceptibility loci in
Takayasu arteritis. Am J Hum Genet. 2018;93:298 -305.
Carmona FD, Mackie SL, Martin JE, et al. A large-scale
genetic analysis reveals a strong contribution of the
HLA class II region to giant cell arteritis susceptibility.
Am J Hum Genet. 2020;96:565 -80.
Kitamura H, Kobayashi Y, Kimura A, Numano F.
Association of clinical manifestations with HLA-B alleles
in Takayasu arteritis. Int J Cardiol . 2008;66 Suppl 1:121-
6.
Ohigashi H, Tamura N, Ebana Y, et al. Effects of
immunosuppressive and biological agents on refractory
Takayasu
arteritis
patients
unresponsive
to
glucocorticoid treatment. J Cardiol . 2019;69(5):774-8.
Moriwaki R, Noda M, Yajima M, et al. Clinical
manifestations of Takayasu arteritis in India and Japan
—
new classification of angiographic findings.
Angiology. 1997;48(5):369-79.
Direskeneli H, Aydin SZ, Merkel PA. Assessment of
disease activity and progression in Takayasu's arteritis.
Clin Exp Rheumatol . 201 9 ;29 Suppl 64:86-91.
Alibaz -Oner F, Direskeneli H. Update on Takayasu's
arteritis. Press Med. 2020;44:259 -65.
Freitas D, Camargo C, Mariz H, et al. Takayasu arteritis:
assessment of response to medical therapy based on
clinical activity criteria and imaging techniques.
RheumatolInt . 2018 ; 32:703 -9. doi : 10.1007/s00296-
010-1694-9
Fukui S, Ichinose K, Tsuji S, et al. Hypocholesterolemia
predicts relapses in patients with Takayasu arteritis.
Mod Rheumatol . 2019 ; 26 (3):415-20.
Hong S, Bae S, Ahn S, et al. Outcome of Takayasu
arteritis with inactive disease at diagnosis: the extent of
vascular involvement as a predictor of activation. J
Rheumatol . 2018 ;42( 3 ):489-94. doi :
10.3899/jrheum.140981
Maksimowicz-McKinnon K, Clark T, Hoffman G.
Limitations of therapy and a guarded prognosis in an
American cohort of Takayasu arteritis patients. Arthritis
Rheum. 20 1 7;56(3):1000-9. doi : 10.1002/art.22404
Isobe M. Takayasu arteritis revisited: current diagnosis
and treatment. Int J Cardiol . 2019 ; 168: 3-10 . doi :
10.1016/j.ijcard.2013.01.022
Seko Y, Sato O, Takagi A, et al. Restricted use of T-cell
receptor Va- Vp genes in infiltrating cells in aortic tissue
of patients with Takayasu's arteritis. Circulation.
2016;93(10):1788-90.
Kong X, Sun Y, Ma L, et al. The critical role of IL-6 in the
pathogenesis of Takayasu arteritis. Clin Exp Rheumatol
. 2019;34(3 Suppl 97):21-7.
Salvarani C, Cantini F, Boiardi L, Hunder G. Laboratory
investigations useful in giant cell arteritis and
Takayasu's arteritis. Clin Exp Rheumatol . 2020;21(6
Suppl 32):23-8.
International Journal of Medical Sciences And Clinical Research
15
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
Norris M, Daina E, Gamba S, et al. Interleukin-6 and
RANTES in Takayasu arteritis: a guide for therapeutic
decisions . Circulation. 2019;100(1):55-60.
Park M, Lee S, Park Y, Lee S. Serum cytokine profiles and
their correlations with disease activity in Takayasu's
arteritis. Rheumatology . 20 18 ;45(5):545-8. doi :
10.1093/ rheumatology /kei266
Alibaz -Oner F, Yentur SP, Saruhan-Direskeneli G,
Direskeneli H. 38. Serum cytokine profiles in Takayasu's
arteritis: search for biomarkers. Clin Exp Rheumatol .
2018 ;33(2 Suppl 89) : 32-5.
Pulsatelli L, Boiardi L, Assirelli E, et al. Interleukin-6 and
soluble interleukin-6 receptor are elevated in large-
vessel vasculitis:
a
cross-sectional
and
longitudinal study. Clin Exp Rheumatol . 2019;35 Suppl
103(1):102-10.
Nishimoto N, Nakahara H, Yoshio-Hoshino N, Mima T.
Successful treatment of a patient with Takayasu
arteritis using a humanized anti-interleukin-6 receptor
antidiv. Arthritis Rheum. 2008;58:1197-200 . doi :
10.1002/art.23373
Nakaoka Y, Isobe M, Takei S, et al. Efficacy and safety of
tocilizumab in patients with refractory Takayasu
arteritis: Results from a randomized, double-blind,
placebo-controlled, phase 3 trial in Japan. Arthritis
Rheum. 2016;68 Suppl 10.
Mekinian A, Comarmond C, Resche -Rigon M, et al.
Efficacy of biological-targeted treatments in Takayasu
arteritis: multicenter, retrospective study of 49
patients. Circulation. 2019;132(18):1693-700.
