Alerji tedavisinde biyolojik tedavi ler. Doç Dr. Arzu Didem YALÇIN..

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

29.  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.

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

36. 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

45.  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

46.  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

47. 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

48.  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

50.  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.

59.  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:

60.  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.

62.  Biologicals targeting IL-17 include an anti-IL-17A mAb: secukinumab and an anti-IL- 17 receptor
mAb: brodalumab. Although the inhibition of IL-17 receptor A had no effect on subjects with
asthma as a whole, a subgroup analysis showed an effect with uncertain significance. Further
studies are needed to determine the role of secukinumab in asthma .

Secukinumab(Anti-IL-17A)
Brodalumab(antiIL-17r, AMG 827)

63. Brodalumab is a human, anti–IL-17RA immunoglobulin G2 (IgG2)
monoclonal antibody that binds with high affinity to human IL-17RA,
blocking the biologic activity of IL- 17A, -17F, -17A/F heterodimer, and -17E
(IL-25). In a randomized controlled study were 302 patients taking this drug
evaluated and at the end of the study there was no evidence for an effect of
brodalumab in these patients.
 Busse WW, (2013): Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate
to severe asthma. Am J Respir Crit Care Med. Dec 1;188(11):1294-302. doi: 10.1164/rccm.201212-2318OC

64.  Allergen exposure can stimulate IL-2 and its receptor expression (IL -
2R) a chain (sCD25) in airways of patients with severe asthma.
Daclizumab is a humanized monoclonal antibody that binds
specifically to the a subunit (CD25) of the high-affinity IL-2R, and
inhibits IL-2 binding and its biological activity. Daclizumab can inhibit
various T cell functions, including T cell proliferation and cytokine
production. It has been investigated in a randomized controlled study.
Anti- IL2 (Daclizumab)

66. The risk of immunosuppression in clinical practice needs to be clarified.

67.  Gauvreau GM, O’Byrne PM, Boulet LP, et al: Effects of an anti-TSLP antibody on allergen-induced
asthmatic responses. N Engl J Med. May 29;370(22):2102-10. doi: 10.1056/NEJMoa1402895.
Antithymic stromal lymphopoietin
(AMG 157, Tezepelumab)
AMG 157 Randomly assigned 31 patients
with mild allergic asthma received AMG 157
(700 mg) or placebo intravenously, once a
month for three doses. The primary outcome,
the maximum percentage decrease in the FEV
during the late asthmatic response was 45.9
percent less in the AMG 157 group than the
placebo group on day 84.
AMG 157 reduced allergen induced
bronchoconstriction and airway
inflammation.
No serious adverse effects were reported.
Further studies on this drug are planned to
clarify its use in clinical practice

72.  Infliximab (Recombinant human–murine chimeric anti-TNFa monoclonal
antibody), etanercept (Soluble TNFa receptor fusion protein), and
golimumab (Fully human TNFa-blocking antibody)
Infliximab, etanercept, golimumab

73. Treatment with golimumab did not demonstrate a favorable risk-benefit
profile in patients with severe persistent asthma . A study with etanercept
showed a small decrease in asthma exacerbations was observed in a
randomized placebo controlled study .

80. 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?

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