1.
 In two studies which used omalizumab in a group of patients
with non-atopic severe asthma, the authors observed
downregulation of FcRI expression in the
basophils and increased FEV1.
 Garcia G, Magnan A, Chiron R, et al : A proof-of-concept, randomized,
controlled trial of omalizumab in patients with severe, difficult-to-control,
nonatopic asthma. Chest. Aug;144(2):411-9. doi: 10.1378/chest.12-1961
NON-ATOPIC ASTHMA

2.
Chang TW. The pharmacological basis of anti-IgE
therapy. Nature Biotechnol. 2000 Feb;18(2):157-
62.

3.
 Astım Olgularının Omalizumaba Maruz
Kalmış Bebekleri
 Bilun Gemicioğlu, Arzu Didem Yalçın, Gül Karakaya, Levent Özdemir,
Metin Keren, Arzu Yorgancıoğlu, Dane Ediger, Sevim Bavbek, Yavuz
Havlucu, Zeynep Ferhan Özşeker
 Omalizumab on yılı aşan bir süredir ülkemizde astımda kullanılan ilk biyolojik tedavidir. Hekim ve hastalarda
hamilelikte kullanımına ait çekinceler bulunmaktadır. Bu araştırma ile omalizumab kullanarak hamile kalıp bir
bebek dünyaya getirmiş Türkiye’deki astım hastalarında anne ve bebeklerin durumu ortaya konmak istenmiştir.
 En az 6 aydır omalizumab kullanan ve en az bir doz omalizumab maruziyeti olmuş bebekleri olan hastalar,
yapılan çağrıya cevap veren merkezlerden belirlenmiştir. Standart anket ile olguların demografik verileri,
hastalığına ve tedavisine ait bilgiler ve hamilelikte aldığı tedaviler, bebekle ilgili sağlık bilgileri retrospektif
olarak araştırılmıştır.
 Astım süresi 12.2±8.1 yıl, total IgE düzeyi 242.1±128.8 İU olan 19 olguya ait 22 bebeğin
omalizumab maruziyeti ile doğduğu belirlenmiştir. 2 olgunun 2 bebeği, bir olgunun da ikizi olup
diğer 16 olgunun tek bebeklerinde omalizumab maruziyeti olmuştur. Anne doğum yaşı ortalaması 31.8±7.2
olup, 22 ile 47 arasında değişmektedir. Hamilelik öncesi ortalama omalizumab maruziyeti 28.9±21.8 aydır. 9
olgunun ilk bebeği olduğu görülmüştür. Bebeklerin omalizumaba maruziyeti ikiz olan 2 bebekte tek doz, 1
bebekte ilk trimestre, 4 bebekte 2 ve 3. trimestre ve 15 bebekte tüm hamilelik ve emzirme dönemi olmak üzere
değişiklik göstermektedir. Olguların omalizumab başlangıç FEV1 ortalamaları 2.5±0.8 lt (%72±19) olup hamilelik
başlangıcında 3.4±0.9lt (%85.3±11.9) olduğu gözlenmiştir. Hamilelik bitiminde de ortalama FEV1 değeri 2.89±0.7
lt (%83.6±2.5) saptanmıştır. Hamilelik döneminde 10 bebek sırasında acil başvuru olduğu gözlenmiştir.
 Bebeklerin hiç birinde anomali gözlenmemiştir. Doğum APGAR indeksi ortalaması 8.7±1.2 bulunmuştur.
Doğum kilosunun 3850gr ile 1850gr arasında değiştiği ortalama 3080.7±566.1gr olduğu görülmüştür.
 Omalizumabın hamilelikte anne ve bebek için olgularımızda güvenli olduğu kararına varılmıştır.

4.
Chang TW. The pharmacological basis of anti-IgE
therapy. Nature Biotechnol. 2000 Feb;18(2):157-62.

5.
ANTI-IgE: OFF-LABEL USE
1. Asthma-COPD overlap syndrome (ACOS)
2. NASAL POLYPOSIS, Samter's syndrome.
3. ALLERGIC RHINITIS, (specific immunotherapy [SIT]+omalizumab)
4. ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
5. ATOPIC DERMATITIS, FOOD ALLERGY
6. ANAPHYLAXIS, Drug Allergy
7. TEN, Bullous pemphigoid, Netherton syndrome, eosinophillic esophagitis
8. NON-ATOPIC ASTHMA
1. Yalcin AD, :Omalizumab (anti-IgE) therapy in the asthma-COPD overlap syndrome (ACOS) and its effects on
circulating cytokine levels. Immunopharmacol Immunotoxicol. Jun;38(3):253-6. doi:
10.3109/08923973.2016.1173057. 2016
2. Uzun R, Yalcin AD, et al : Levofloxacin Induced Toxic Epidermal Necrolysis: Successful Therapy with
Omalizumab (Anti-IgE) and Pulse Prednisolone. Am J Case Rep. Sep 16;17:666-71. 2016
3. Yalcin AD : A case of netherton syndrome: successful treatment with omalizumab and pulse prednisolone and
its effects on cytokines and immunoglobulin levels. Immunopharmacol Immunotoxicol.;38(2):162- 6. doi:
10.3109/08923973.2015.1115518. 2016
4. Yalcin AD, et al :Anti-IgE monoclonal antibody (omalizumab) is effective in treating bullous pemphigoid and
its effects on soluble CD200. 2014 Clin Lab.60(3):523-4.
5. Yalcin AD, et al. Effects of Omalizumab on Eosinophil Cationic Peptid, 25-Hydroxyvitamin-D, IL-1ß, and
sCD200 in a cases of Samter's syndrome: 36 Months follow-up. Immunopharmacology And Immunotoxicology
doi:10.3109/08923973.213.811598.
6. Yalcin AD, et al. Clinical Experience in Allergic Asthma Patients: Omalizumab with Immunotherapy. World

6.
 Navinés-Ferrer A, et al (2016). IgERelated Chronic Diseases and Anti-IgE-Based Treatments. J
Immunol Res.;2016:8163803. doi: 10.1155/2016/8163803.
ALLERGIC RHINITIS

7.
 In 2007, a randomized placebo-controlled study of eight patients was the
first to report reduced rates of postoperative polyp recurrence in patients
with atopic asthma and nasal polyps (NP) [1].
 Tajiri et al [3] evaluated omalizumab in patients with severe asthma and NP,
and reported significant improvements in
 nasal symptoms, asthma control, and sinus tomography results. However,
not all studies were able to show the beneficial effects of the treatment. In a
randomized, double-blind, placebo-controlled study of patients with
chronic rhinosinusitis receiving omalizumab, Pinto et al. [4] showed
improvement in the Sino-Nasal Outcome Test (SNOT-20) scores at three,
five, and six months, although there was no significant difference in the
scores compared to the control group.
 1. Hong CJ (2015): Anti-IgE monoclonal antibody therapy for the treatment of chronic rhinosinusitis: a systematic
review. Syst Rev. Nov 18;4:166. doi: 10.1186/s13643-015-0157-5.
 2. Vennera Mdel C, et al (2011): Efficacy of omalizumab in the treatment of nasal polyps. Thorax. Sep;66(9):824-5.
doi: 10.1136/thx.2010.152835.
 3. Tajiri T, et al (2013): Efficacy of omalizumab in eosinophilic chronic rhinosinusitis patients with asthma. Ann
Allergy Asthma Immunol. May;110(5):387-8. doi: 10.1016/j.anai.2013.01.024
 4. Pinto JM, Mehta N, DiTineo M, et al (2010): A randomized, double-blind, placebo- controlled trial of anti-IgE for
chronic rhinosinusitis. Rhinology. Sep;48(3):318-24. doi: 10.4193/Rhin09.144.
Nasal polips

8.
Are nasal function impairment and nasal airflow affected by
omalizumab therapy in patient with allergic rhinitis and
nasal polips?
Arzu Didem Yalçın, Murat Toprak, Bülent Tutluoğlu, Bert Schmelzer

9.
 Wenzel S, Castro M, Corren J, et al (2016): Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high- dose
inhaled corticosteroids plus a long-acting ß2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016 Jul
2;388(10039):31-44. doi: 10.1016/S0140-6736(16)30307-5.
Anti-IL-4/IL-13 Molecules
• Dupilumab is a drug that inhibits signaling from IL- 4 and IL-13 concomitantly. It
is a molecule that binds to the alpha subunit of the IL-4 receptor.

10.
 Mepolizumab and Reslizumab, binds directly to IL-5 ligand. These molecules effectively
decreased circulating and sputum eosinophil counts, but they failed to improve airway mucosal
eosinophilia, acute exacerbation rates, lung function and symptom scores in several studies.
 Benralizumab (MEDI-563): a humanized recombinant IgG1-k isotype monoclonal antibody)are
new developed monoclonal antibodies that target the cytokine IL-5.
Anti-IL-5 Molecules:

11.
 Anti-IL5 therapies for asthma could be safe for slightly improving FEV1 (or FEV1% of predicted
value), quality of life, and reducing exacerbations risk and blood and sputum eosinophils. However
these drugs have no significant effect on PEF, and SABA rescue use.
 Khorasanizadeh M, et al : Efficacy and Safety of Benralizumab, a Monoclonal Antibody against IL-
5Ra, in Uncontrolled Eosinophilic Asthma. Int Rev Immunol. 2016 Jul 3;35(4):294-311.

12.
22. Yalcin AD, Bulut T, Celik B, Genc GE, Gocmen AY, Gumuslu S. Are
thermogenic proteins and adipokine chemerin affected by monoclonal
antibody therapy in asthma? Eurasian J Pulmonol doi:
10.4103/ejop.ejop_60_18.
23. Uzun R, Yalcin AD, Bulut T, Tutluoğlu B. Future Perspective:
Anti-IgE treatment in Asthma with Bronchiectasis and its effects on
sCD200, circulating cytokines: Long-term follow-up. Current Pharma
Biotecnology 2019
24. Yalcin AD, Uzun R. Omalizumab significantly changes
circulating interleukin-25, and interleukin-33 levels in patients with
allergic asthma . Current Pharma Desing 2019.
25. Uzun R, Yalcin AD, Omalizumab increases circulating interleukin-
10Rb, interleukin-22 levels in responsive patients with severe persistent
allergic asthma.
26. Yalcin AD, Uzun R, Tutluoglu B, Toprak M, Shmelzer B. New
perspective: Are nasal function impairment and nasal airflow affected
by omalizumab therapy in patient with allergic rhinitis and nasal
polips?

13.
Sunum Bilgileri:
Sunum No: SS-021
Oturum Kodu: SSO 3 -
Sözlü Sunum 3
Tarih ve Saat: 28.10.2019 /
17:45-19:00
Salon: SALON T3

14.
Future Perspective: Anti-IgE
treatment in Asthma with
Bronchiectasis and its effects on
sCD200, circulating cytokines:
Long-term follow-up

15.
MATERIAL and METHODS
 The study included 11 BR patients with asthma, 3 of whom had a history
of CIU, 2 had FDE (a fixed drug eruption) and 2 had thrombosis (Table-
2)
 Blood samples were collected at all follow-up visits from the time of first
diagnosis (pre-omalizumab period) until 36 months after treatment
during disease remission (post-omalizumab period). The clinical
changes and adverse effects were evaluated at each bi-monthly patient
visit, including vital signs, full physical examination, details of any
allergy incidents, total and specific (mite, grass, mold, tree) IgE levels,
serum ECP levels, pulmonary function tests (FEV1/FVC rates), exhaled
nitric oxide (FENO) concentrations and asthma control test (ACT)
(Quality Metric Incorp). Medical history, lung function tests, and
measurement of exhaled nitric oxide concentrations (FENO) were
performed on the same day. The use of additional steroid and
omalizumab therapy were recorded with the doses given (Table 2).

16.
Sunum Bilgileri:
Sunum No: OK -10
Oturum Kodu: OKO 2-
Olgu Konseyi-2
Tarih ve Saat: 27.10.2019 /
17:45-19:00
Salon: SALON T3

17.
 Context: Anakinra is a human IL-1 receptor
antagonist produced in Escherichia coli cells by
recombinant DNA technology . Anakinra
competitively inhibits IL-1α and IL-1β from
binding to the IL-1 type I receptor, thereby
neutralizing the activity of these key mediators
of immune and infammatory processes.
 Schnitzler syndrome (SchS) is a rare
inflammatory disorder characterized by chronic
urticarial exanthema, joint and bone alterations,
monoclonal gammopathy and fever, which
manifest mostly in the second half of life.

18.
 First described in 1972 by the dermatologist Dr. Liliane
Schnitzler , the disorder is diagnosed when patients
meet the Strasbourg criteria. This includes two obligate
criteria: recurrent, monoclonal gammopathy and
nonpruritic chronic urticaria .
 At least two of the following minor criteria are also
required: recurrent fever, objective findings of abnormal
bone remodeling with or without bone pain, neutrophilic
dermal infiltrate on skin biopsy, and elevated acute
phase reactants (CRP and/or leukocytosis)

19.
 Methods: The patient is a 51-year-old white Caucasian male with a past medical history of hypertension,
hyperlipidemia, mite allergy, asthma and diabetes mellutus who presented with complaints of joint pains
for over 25 years. He was started on anakinra 100 mg subcutaneous daily. All steroid treatment was stopped a
month later.
 Experimental procedures
 Blood samples were taken at all follow up visits from the time of first diagnosis (pre-anakinra
period), after 4 and 12 months of treatment during disease remission (postanakinra period).
This study was approved by the local ethics committee (Academia Sinica, Taiwan, Taipei),
and written informed consent was obtained from the patient. Blood samples measurement
were always taken in the morning between 8 and 9 am. IL-1 β, IL-33, IL-25, IL-8 and IL-17A
levels were measured using ELISA kit (IL-33 : Human IL-33(Interleukin 33) ELISA Kit, Cat
Number: E-EL-H2402, Elabscience ; Human IL-25(Interleukin 25) ELISA Kit, Cat Number: E-
EL-H1648, Elabscience). Total and specific IgE levels were enumerated by fluoroenzyme
immunoassay (ImmunoCAP-FEIA) using an ImmunoCAP (Pharmacia, Uppsala, Sweden) kit.
Values above 100 and 0.35 kU/L for total and specific IgE levels were considered abnormal.
hCRP levels were measured using a CRP-assay (Behring-Latex- Enhanced using the Behring
Nephelometer, BN-100; Behring Diagnostics, Westwood, MA). The sensitivity of the assay
ranged 0.04–5.0 mg/L. Serum levels of 25(OH)D were quantified by a radioimmunoassay and
categorized into sufficient (30 ng/mL), deficient (<20 ng/mL) or insufficient (20 to <30 ng/mL)
based on current recommendations (Cobra Quantum, Packard, MN, USA). The results were
reported as means of duplicate measurements.

20.
 Results:
 Having undergone arakinra treatment and a short-
term later, he had a decreased IgE, Ferritin, ESR,ECP,
d-dimer, hsCRP, IL-33, IL-25, IL-1b, IL-8 and IL-17A
levels. The patient noticed significant improvement
in her urticarial rash within days after initiating the
anakinra.

21.
 Conclusion: We believe that circulating
cytokines may also have an important role for
the relationship between SchS and chronic
inflammation. Further studies are needed to
investigate whether the Th2-mediated
inflammation system has a role and an effect
of cytokines as markers in SchS.

22.
{ {
adidyal@yahoo.com
linkedin.com/in/%E5%A7%9A%E6%99%B6%E6%84%9B-arzu-didem-yalcin-b788a030
scholar.google.com.tr/citations?user=NjsQBgkAAAAJ&hl=trmobile.twitter.com/adidyal
linkedin.com/mynetwork/invitation-manager
scholar.google.com.tr/citations?user=NjsQBgkAAAAJ&hl=tr
researchgate.net/profile/Arzu_Yalcin