Atopik Hastalarda monoklonal Antikor tedavileri, Human(ized) monoclonal antibodies in Atopic patients - State of art. C.European J. Immunology 2018

3. Atopik Hastalarda monoklonal
Antikor tedavileri
 Human(ized) monoclonal antibodies in Atopic
patients - State of art. C.European J. Immunology 2018

10. Jennifer McCracken, MD, BIOLOGIC THERAPY IN THE MANAGEMENT OF
ASTHMA. Curr Opin Allergy Clin Immunol. 2016 Aug; 16(4): 375–382.
Target Treatment Stage of Development
IgE Omalizumab Marketed
IL-5 Mepolizumab
Reslizumab
Marketed
IL-5R Benralizumab Phase III
IL-4Rα (IL-4/IL-13) Dupilumab
Pitrakinra
Phase III
Phase II
IL-13 Lebrikizumab
Tralokinumab
Phase III
Phase III
IL-17 Secukinumab
Brodalumab
Phase II
Phase II

12. Omalizumab and quilizumab
(directed against an extracellular 52-aminoacid segment termed M1 prime of human membrane IgE
through reduction of new IgE-producing plasma cells)

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

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

27. 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 Allergy Organ J. 2012;5(Suppl 2):S105.

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

29. Nasal polips
 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.

30. NON-ATOPIC ASTHMA
 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

32. Anti-IL-4/IL-13 Molecules
 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.
• 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.

33. MEDI-528 has been studied in a clinical trial on 327 asthmatic subjects. Patients were
randomized to receive placebo or one of three doses of MEDI-528 (dosage 30, 100, or 300 mg
s.c. twice weekly for 4 weeks) in addition to their usual asthma medications.
The addition of MEDI-528 to existing asthma controller medications did not improve ACQ-
6 scores, asthma exacerbation rates, or FEV1 values.
Pascolizumab and VAK694 are anti-IL-4 neutralizing monoclonal antibodies. Also IL-4
receptor antagonist drugs like dupilumab, pitrakinra and AMG-317 have been discovered.
Even a recombinant IL-4Ra that captures soluble IL-4 and prevents their binding to IL-4
receptors, has been developed. It is called altrakincept.

37. Anti-IL-5 Molecules:
 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.

38.  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.

40. Secukinumab(Anti-IL-17A mAb)
Brodalumab(anti-IL- 17 receptor mAb, AMG 827 )
 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.

41. 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

42. Anti- IL2 (Daclizumab)
 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. The drug
has the potential to improve pulmonary function and asthma control in patients
moderate to severe chronic asthma

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

45. Antithymic stromal lymphopoietin
(AMG 157, Tezepelumab)
 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.
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.

48.  In a case-series report was it told that in severe, uncontrolled, steroid-
dependent asthma infliximab could reduce exacerbations and
hospitalizations .


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

50. 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 .

54.  22. 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. Austria,Vienna, EAACI, ORAL
PRESANTATİON. 2017
 23. 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. WAO 2015.
 24. 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. WAO 2016
 25. Yalcin AD, et al. Effects of Human(ized) Anti-IgE monoclonal antibody on circulating
adipocytokines and thermogenic proteins. İn press. 2019. Tailand, Bankok, APSR ORAL
PRESENTATİON 2015.
 26. Yalcin AD. Human(ized) monoclonal antibodies in Atopic patients - State of art. Review.
C.European J. Immunology 2018. Ukraina, Kiev, 3rd EURASIAN RESPIRATORY & ALLERGY
SUMMIT Sep 6-9 (ORAL PRESENTATİON) 2018.
 27. Yalcin AD, et al. Clinical Experience in Allergic Asthma Patients: Omalizumab with
Immunotherapy. World Allergy Organ J. 2012;5(Suppl 2):S105. WAO 2012.
 28. Yalcin AD, et al. Human(ized) Anti-IgE monoclonal antibody terapyin the Exercise-Induced
Asthma .Ukraina, Kiev, 3rd EURASIAN RESPIRATORY & ALLERGY SUMMIT Sep 6-9 (ORAL
PRESENTATİON) 2018.
29. Yalcin AD, et al. Omalizumab is effective in treating severe asthma in patients with coagulation
disorders and its effects on Cytokines, Protein C and S; Long term follow-up(RESEARCH). İn press
2019
30. Yalcin AD.Human(ized) Monoclonal Antibodies in Asthma: Future Perspectives. Journal of
Allergy and Therapy, 7(4), Doi: 10.4172/2155-6121.1000e115. Editorial. (Meditrio. CYPRUS 4-7

55.  31. Yalcin AD. Et al. Humanized Monoclonal Antibodies in Pulmonology: An
Integrated Review. Internal Medicine Research - Open Journal, 2(1), 1-6., (Kontrol No:
4198061).2017
 32 Yalcin AD. Biological Agents in Asthma Therapy: An Overview. Immune System
and Disorder Journal, 1(1), 1-2., (Kontrol No: 3461354). 2017.
 33. Tural S. Ö, Yalcin AD. Effects of Omalizumab Treatment on Some Biomarkers in
Severe Allergic Asthma Patients. Eurasian Journal of Pulmonology, 19(2), 84-90., Doi:
10.5152/ejp.2017.64935, 2017. 2017
 34. Yorgancıoğlu A, Öner Erkekol F, Mungan D, Erdinç M, Gemicioğlu B, Özşeker ZF,
Bayrak Değirmenci P, Naycı S, Çilli A, Erdenen F, Kırmaz C, Ediger D, Yalçın AD,
Büyüköztürk S, Öztürk S, Güleç M, Işık SR, Kalyoncu AF, Göksel Ö, Aydın Ö, Havlucu Y,
Baloğlu Ar İ, Erdoğdu A. Long-Term Omalizumab Treatment: A Multicenter, Real-
Life, 5-Year Trial. Int Arch Allergy Immunol. 2018;176(3-4):225-233. doi:
10.1159/000488349. Epub 2018 May 17. PMID: 29772578 . ERS 2017

56. adidyal@yahoo.com
https://www.researchgate.net/profile/Arzu_Yalcin
Anti-IgE program - Tribute to hundreds of colleagues and collaborators for their contribution
CemX development – Cheng Peng, Frances Davis, Huan Yuan Chen, Jiun-Bo Chen, Pheidias Wu, Alfur Hung,
Chien-Jen Lin, Hsing-Mao Chu, Jonathan Wright, and many others
Prof. Dr. Bülent Tutluoğlu
Prof. Dr. Bahattin Çolakoğlu
Prof. Dr. Murat Toprak
Prof. Dr. Ahmet Başustaoğlu
Prof. Dr Teyfik Turgut
and. Akademik Solunum
Derneği