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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 12  |  Issue : 3  |  Page : 175-178

Clinical efficacy and safety of combined house dust mite subcutaneous immunotherapy and omalizumab in five cases of allergic rhinitis and asthma


1 Department of Allergy/ Asthma BLK Hospital and Director at National Allergy Center, New Delhi, India
2 National Allergy Centre, New Delhi and BLK Superspeciality Hopital, New Delhi, India

Date of Submission22-Jan-2021
Date of Decision12-Feb-2021
Date of Acceptance17-Feb-2021
Date of Web Publication30-Jul-2021

Correspondence Address:
Dr. P C Kathuria
1/3 East Patel Nagar, New Delhi - 110 008
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injms.injms_7_21

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  Abstract 


Allergen immunotherapy (AIT) is a well-recognized treatment for altering the natural course of respiratory allergy which builds immune tolerance and prevents progression of allergic diseases. In our five cases of house dust mite (HDM)-driven allergic rhinitis and asthma, combined HDM Subcutaneous Immunotherapy (HDM-SCIT) for 2 years with omalizumab for more than 12 months has achieved disease remission in four cases and disease control in one case along with long-term effect for 3 years after discontinuation of AIT. We hypothesize that combining HDM-SCIT and omalizumab is a promising strategy as it is effective, safe, and synergistic having immune-modifying activity in cases of HDM-driven Allergic Rhinitis and Asthma.

Keywords: Allergen immunotherapy, asthma, corticosteroids, Dermatophagoides farinae, dermatophagoides pteronyssinus, house dust mite, omalizumab, rhinitis


How to cite this article:
Kathuria P C, Rai M. Clinical efficacy and safety of combined house dust mite subcutaneous immunotherapy and omalizumab in five cases of allergic rhinitis and asthma. Indian J Med Spec 2021;12:175-8

How to cite this URL:
Kathuria P C, Rai M. Clinical efficacy and safety of combined house dust mite subcutaneous immunotherapy and omalizumab in five cases of allergic rhinitis and asthma. Indian J Med Spec [serial online] 2021 [cited 2021 Sep 19];12:175-8. Available from: http://www.ijms.in/text.asp?2021/12/3/175/322783




  Introduction Top


Genetic predisposition and environmental exposures are known to be risk factors for asthma. House dust mite (HDM) allergen such as Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df) plays a major part in allergic diseases and is a globally important indoor allergen to cause allergic rhinitis and asthma. In one cross-sectional study of 628 allergic rhinitis patients, 50% of them were sensitized to HDM and 45%–85% of asthmatics were sensitized to mites.[1] In the Copenhagen allergy trial, 50% of subjects with HDM-induced rhinitis have HDM-induced asthma, while 95% of HDM-induced asthma also had HDM-induced rhinitis.[2] Exposure in early childhood to HDM allergens has been found to be a significant determinant of allergic manifestations and the subsequent development of asthma. Asthmatics sensitized to HDM have been found to have a lower forced expiratory volume (FEV) and FEV1/forced vital capacity ratio than asthmatics without sensitization.[3]

Omalizumab (Xolair, Genentech/Novartis) is a monoclonal anti-IgE antibody that has been used to reduce sensitivity to allergens. It specifically binds to the IgE molecule at the same epitope of FcεRI. Pretreatment by omalizumab before immunotherapy initiation in children and young adults with severe asthma has been reported to increase tolerability to therapy, decrease side effects, and amplify the efficacy of subcutaneous immunotherapy (SCIT).[4],[5] A randomized, double-blind, placebo-controlled trial published in 2013 confirmed the efficacy, safety, and the long-lasting effect of SCIT combined with omalizumab.[6]


  Case Reports Top


Case discussion

Case 1

A 21-year-old male, perennial allergic rhinitis and asthma for 13 years, presented with a history of recurrent, sneezing, rhinorrhea, nose block, watering eyes, shortness of breath, and cough. Symptoms aggravate during the months of September-October. He was symptomatic in spite of regular intake of 900 μg/18 μg of inhaled corticosteroid (ICS) and Long-Acting Beta Agonist (LABA), montelukast-10 mg per day and on and off oral corticosteroids (OCS). Clinical characteristics and objective parameters are shown in [Table 1].
Table 1: Clinical characteristics of cases 1, 2 and 3

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Case 2

A 41-year-old male, perennial allergic rhinitis and asthma, presented with recurrent episodes of sore throat, cough/wheezing, sneezing, rhinorrhea, and itching/watering eyes for the last 25 years. The symptoms exacerbate during the months of March/April and August/September. He was symptomatic in spite of regular intake of 900 μg/18 μg of ICS and LABA, montelukast-10 mg per day, and on and off OCS. Clinical characteristics and objective parameters are shown in [Table 1].

Case 3

A 19-year-old male, perennial allergic rhinitis and asthma, presented with recurrent episodes of sneezing, rhinorrhea, nose block, headache, shortness of breath, and cough on and off for 4 years. He was well controlled on a regular intake of 600 μg/12 μg of ICS and LABA and montelukast-10 mg per day. Clinical characteristics and objective parameters are shown in [Table 1].

Case 4

61 years old male, a case of perennial allergic rhinitis with intermittent asthma, food allergy to milk, red & green chillies, capsicum and wheat and history of contact dermatitis to hair dye. Symptoms are perennial and get aggravated on exposure to dust. He was symptomatic in spite of regular intake of 900 μg/18 μg of ICS and LABA, cetirizine-10 mg, and montelukast-10 mg with topical steroid. Clinical characteristics and objective parameters are shown in [Table 2].
Table 2: Clinical characteristics of cases 4 and 5

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Case 5

A 22-year-old male, perennial allergic rhinitis and asthma, also had a history of atopic dermatitis (generalized itching with redness and dryness) and food allergy (milk, wheat, fish, dry fruits, and yogurt) for 4 years. Symptoms aggravate during nighttime and on exposure to dusty weather and sunlight. He was on 1200 μg/24 μg of ICS and LABA, montelukast-10 mg, antihistamines, and topical steroids with on and off OCS. Clinical characteristics and objective parameters are shown in [Table 2].

Recommendation of cases

All the five cases were given combined HDM-SCIT (HDM, 10000 AU per ml SCIT Greer Laboratories, Inc.) with effective dose (gradual up-dosing protocol of buildup phase to achieve maintenance dose [MD]-500 AU per month) for 2 years and Anti-IgE (injection omalizumab [150 mg] ×15 days before allergen immunotherapy [AIT], followed by once a month for variable duration) (case 1 for 14 months, case 2 for 20 months, case 3 for 14 months, case 4 for 21 months, and case 5 for 17 months). Disease remission was seen in four cases (cases 1–4) and disease control in one case (case 5).


  Discussion Top


There is no diagnostic tool or algorithm to discriminate between HDM-driven allergic asthma and asthma with HDM sensitization. An accurate diagnosis of HDM-driven allergic asthma includes (a) evidence of allergic sensitization (SPT and specific IgE) to HDM and (b) confirmation of HDM exposure as the main driver of asthma symptoms as per history. Allergen provocation (airway hyperreactivity testing may be required in some cases.[7] HDM activates not only adaptive and T helper 2 cells (Th2) derived immune response but also innate immunity.

Our patients of HDM-driven allergy rhinitis and asthma, with history of early onset of symptoms, elevated Total IgE and specific IgE to HDM (100 Kua/L in three cases), SPT >8 mm wheal size, increased absolute eosinophil count (>500 cells/uL) were symptomatic despite the correct use of ICS/LABA, but when OCS (oral corticosteroids) was added, their symptom control or normalization of PEFR (peak expiratory flow rate)/lung function was achieved.

AIT is the only known therapy to alter the natural course of respiratory allergy by targeting allergen-activated immune cells such as Th2 and regulatory T cells (Treg) and triggering a sustained effect based on allergen-specific T cell tolerance of inflammation and induction of allergen-specific IgG4.[8] AIT is known to be effective in reducing the risk of asthma onset and has been progressively applied for the treatment of allergic asthma in combination with pharmacological treatment.[9]

In general, AIT has been shown to be effective in reducing symptoms in patients with allergic asthma and has been recommended by national and international guidelines as add-on therapy to pharmacotherapy, or for consideration as an alternative option for patients who are refractory to pharmacotherapy treatment. The 2017 GINA report recommends sublingual immunotherapy as an add-on option for selected adult patients who are HDM sensitized and have exacerbations in asthma and allergic rhinitis despite Step 3 or Step 4 medium-dose ICS treatment, provided FEV1 is 70% predicted.[10]

Symptom and medication scores in allergic rhinitis and asthma are the two most important clinical indicators for the evaluation of the efficacy of AIT. In our five cases, we evaluated ACT, medication scoring, and pulmonary function for the efficacy of AIT and also analyzed the difference in the ratio of HDM specific IgE to total IgE antibodies and skin reactivity to HDM (Dp/Df) after 12 months of combined AIT and omalizumab [Table 1] and [Table 2].

Our five patients underwent SPT (Allergopharma, Germany/Greer Lab, USA) and Specific IgE (Thermofisher, ImmunoCap) to various groups of aeroallergens after giving an informed consent. HDM subcutaneous AIT (HDM-SCIT) was given with effective concentration of 1000 AU per ml. Omalizumab (Anti-IgE) was prescribed 15 days before the start of the buildup dose of HDM extract by cluster immunotherapy with incremental concentration 0.05/0.05 ml, 0.1/0.1 ml, 0.2/0.2 ml, and 0.3/0.2 ml till MD of 0.5 ml of 1000 AU per ml) was achieved [Table 3]. Further MD of HDM-SCIT was continued every 4 weeks for 2 years along with injection omalizumab 150 mg given every 4 weeks varying from 14 to 21 months. None of our patients had a systemic life-threatening reaction during the buildup phase. Premedication with antihistamine and OCS was given 2 h before cluster doses of HDM-SCIT.
Table 3: Schedule and duration of Combined House Dust Mite Subcutaneous Cluster Immunotherapy (HDM-SCIT) (Dp-50%, Df-50% 500 AU per MD) along with Inj Omalizumab therapy.

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The clinical implication in our four cases (Case 1–4) was that they could discontinue ICS/LABA/OCS and achieved remission after 12 months by combining HDM-SCIT with omalizumab (remission is defined as no further requirement of maintenance medications (e.g. ICS/LABA or LTRA for allergic asthma and ICS or nonsedating antihistamines for allergic rhinitis) for at least 1 year of SCIT. while in Case number 5 with h/o allergic rhinitis and asthma with concomitant atopic dermatitis, we could only discontinue OCS and were able to achieve controlled state after 12 months (A controlled state is defined as patients whose symptoms were controlled well with maintenance treatment and required no further intake of OCS and (SABA/nonsedating antihistamine for allergic rhinitis) for at least 1 year of SCIT.

We hypothesize that the combination of omalizumab and HDM-SCIT has an excellent safety profile and might be a promising strategy having immune-modifying activity. This combined therapy not only improved symptom and medication scoring but also enabled our patients to achieve MD of AIT faster in just four visits. We also hypothesize that if history is consistent with HDM sensitization then, single AIT with HDM-SCIT (for 2 years) combined with omalizumab (for 1 year) is enough to achieve remission even if the patient is sensitized to other cross-reactive allergens. We have 3-year follow-up of these five cases with remission of four cases and disease control of one case with long-term effect for 3 years after discontinuation of AIT.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that names and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Acknowledgment

The authors were assisted in the proofreading of the manuscript by Simran Chhatwal, an MSL, working with GSK, India.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
de Vries MP, van den Bemt L, van der Mooren FM, Muris JW, van Schayck CP. The prevalence of house dust mite (HDM) allergy and the use of HDM-impermeable bed covers in a primary care population of patients with persistent asthma in the Netherlands. Prim Care Respir J 2005;14:210-4.  Back to cited text no. 1
    
2.
Biagtan M, Viswanathan R, Bush RK. Immunotherapy for house dust mite sensitivity: Where are the knowledge gaps? Curr Allergy Asthma Rep 2014;14:482.  Back to cited text no. 2
    
3.
Zhang W, Lin C, Sampath V, Nadeau K. Impact of allergen immunotherapy in allergic asthma. Immunotherapy 2018;10:579-93.  Back to cited text no. 3
    
4.
Tsabouri S, Mavroudi A, Feketea G, Guibas GV. Subcutaneous and sublingual immunotherapy in allergic asthma in children. Front. Pediatr 2017;5:82.  Back to cited text no. 4
    
5.
Lambert N, Guiddir T, Amat F, Just J. Pre-treatment by omalizumab allows allergen immunotherapy in children and young adults with severe allergic asthma. Pediatr Allergy Immunol 2014;25:829-32.  Back to cited text no. 5
    
6.
Kopp MV, Hamelmann E, Bendiks M, Zielen S, Kamin W, Bergmann KC, et al. Transient impact of omalizumab in pollen allergic patients undergoing specific immunotherapy. Pediatr Allergy Immunol 2013;24:427-33.  Back to cited text no. 6
    
7.
Agache I, Lau S, Akdis CA, Smolinska S, Bonini M, Cavkaytar O, et al. EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma. Allergy 2019;74:855-73.  Back to cited text no. 7
    
8.
Nagata M, Nakagome K. Allergen immunotherapy in asthma: Current status and future perspectives. Allergol Int 2010;59:15-9.  Back to cited text no. 8
    
9.
Jutel M. Allergen-specific immunotherapy in asthma. Curr Treat Options Allergy 2014;1:213-9.  Back to cited text no. 9
    
10.
Massoud Mahmoudi DO. Allergy and Asthma: Practical Diagnosis and Management. New York, NY, USA: Springer Science+Business Media; 2016.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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