Grass Pollen Subcutaneous Immunotherapy in Elderly Patients
Condition: Allergy
MeSH terms: Hypersensitivity
Study type: Interventional
Phase: Phase 4

Summary: 
      Background There is limited evidence indicating that specific immunotherapy in elderly
      patients is safe and effective. This study was performed to evaluate the safety and efficacy
      of specific subcutaneous immunotherapy (SCIT) against grass pollen allergens in patients over
      60 years of age with seasonal allergic rhinitis (SAR) and a confirmed allergy to grass
      pollen.

      Objective This study assessed the safety and efficacy of SCIT for grass pollen allergens in
      elderly patients with SAR.

      Methods This study included 62 60- to 75-year-old patients with SAR and grass pollen allergy
      confirmed using a skin prick test, nasal provocation, and serum IgE measurement. The patients
      were individually randomized to the active or placebo groups using a double-blinded method.
      There were 33 subjects in the SCIT group (Purethal, Grass pollen, HAL Allergy B.V, Leiden,
      Netherlands) and 29 subjects in the placebo group monitored for three years. The patients
      were required to record each use of anti-allergy medication in a diary and use a visual
      graphic scale. The main outcome measure was the area under the curve (AUC) for the combined
      symptom and medication score (SMS).
    

Detailed description: 
      Methods Patients A total of 109 patients ranging from 60 to 70 years of age were recruited
      from the outpatient allergy clinic to assess their eligibility for inclusion in the study.
      The subjects had moderate or severe intermittent allergic rhinitis and fulfilled the ARIA
      criterion. Additionally, the patients included in the study all had a positive skin prick
      test (SPT), were positive for specific immunoglobulin E (sIgE), and had positive nasal
      provocation tests (NPTs) with grass pollen mixture allergens. Patients with any of the
      following characteristics were excluded from the study: hypersensitivity to other allergens,
      bronchial asthma, non-allergic rhinitis (especially senile or vasomotor rhinitis) and severe
      non-stable diseases. However, patients with stable coronary disease, diabetes, and arterial
      hypertension were permitted in the study. All subjects were required to abstain from
      anti-allergy drugs and glucocorticoid nasal drops for at least 6 weeks prior to the start of
      the study.

      There were 62 patients individually randomized in comparable numbers to one of two "parallel"
      groups using a double-blind method. The groups were the active (n=33) treatment group and the
      placebo (n=29) group. There were 31 subjects in the SCIT group and 25 subjects in the placebo
      group that completed the three-year observation period. The groups were comparable at
      baseline.

      Diagnostic procedures A careful examination of the eyes, ears, nose, and throat was performed
      on all patients. The severity of seasonal allergic rhinitis (SAR) was assessed using the
      Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The patients with other nasal
      problems such as chronic nasal obstruction, reduced olfaction, bacterial colonization, and
      chronic sinusitis were diagnosed based on a CT scan and nasal endoscopy. Several patients
      were excluded from further observation as a result of these problems. The subjects with other
      chronic or acute clinical disorders or with a history of respiratory tract infections within
      four weeks of the study initiation were also excluded. The SPT was performed using inhalant
      allergens (HAL Allergy B.V, Leiden, Netherlands) from the following panel: D. pteronyssinus,
      D. farinae, mixed 5 grasses (Phleum pratense, Dactylis glomerata, Anthoxanthum odoratum,
      Lolium perenne, and Poa pratensis), mixed tree, mugwort, Alternaria, Cladosporium, dog and
      cat allergens. There were also positive (10 mg/ml of histamine) and negative (saline)
      controls included. A grass pollen allergy was defined as having positive skin tests for 5
      grass pollen allergens with a minimum wheal diameter of at least 3 mm greater than the
      negative control. The patients with negative tests for histamine sensitivity were excluded
      from further analyses. The sIgE reactivity to the single grass pollen allergen components
      (Phl p1, Phl p2, Phl p5, Phl p6, Phl p7 and Phl p12) was determined using ImmunoCAP (Phadia
      AB, Uppsala, Sweden) tests. The results were considered positive when the sIgE concentration
      was greater than 0.35 IU/ml (according to the manufacturer's instructions). NPTs were
      conducted using active anterior rhinomanometry with commercial grass pollen mixture
      allergens. The concentration was 10,000 AU/ml and the mixture was delivered as 1 puff per
      nostril (HAL Allergy B.V, Leiden, Netherlands) using the methods described by Bachert et al.
      and Dordal et al. A reduction in the peak nasal inspiratory flow greater than or equal to 40%
      and an increase in symptoms greater than or equal to 5 points were considered to be positive
      NPT criteria by Bachert et al. and Dordal et al. The NPTs were also repeated after three
      years of treatment. The patients monosensitized to grass pollen were included in this study.

      Treatments The patients were randomly selected to receive Purethal Grasses 20,000 AUM/ml
      (pollen mixture extract solution of Agrostis stolonifera, Anthoxanthum odoratum,
      Arrhenatherum elatius, Dactylis glomerata, Festuca rubra, Holcus lanatus, Lolium perenne,
      Phleum pratense, Poa pratensis, Secale cereal, Loe edasi HAL Allergy B.V, Leiden,
      Netherlands) or placebo. The recruitment period was limited to three months
      (October-December). Purethal grasses (January-April) were administered as pre-seasonal
      therapy using the following regimen: 1 dose- 0.1 ml, 2 dose - 0.2 ml, 3 dose - 0.4 ml every
      week, and doses 4- 7 consisted of 0.5 ml every two weeks.

      Using this schedule the average cumulative dose was 460,500 BAU (Bioequivalent Allergy Unit),
      which contains approximately 690 μg of Phl p5 administered to each patient undergoing active
      treatment for all three years of the study. The study consisted of two phases. The first
      phase was the baseline one season of follow-up visits without treatment and the second phase
      was three years of SCIT or placebo.

      Assessment of efficacy The prime outcome measure was the area under the curve (AUC) for
      combined symptom and medication score (SMS) over the grass pollen season for baseline 2010
      (before treatment) and in 2011, 2012 and finally in 2013 after three years of SCIT. The
      patients recorded symptom severity in a daily diary during the pollen season (May-August) by
      scoring the following areas: nasal itching, sneezing, running, blockage, and ocular itch on a
      separate Visual Analog Scale (VAS) with a continuous scale from 0 cm (no symptoms) to 10 cm
      (very severe symptoms). The rescue medication provided and scoring was a one point per spray
      for Azelastine nasal spray or eye drops (Levocabastine), or per 5 mg levocetirizine tablet.
      The score was two points per puff for mometasone fuorate nasal spray and three points per
      prednisolone 10 mg tablet. This combined symptom-medication score was calculated as a sum of
      the symptom score and medication score monitored daily with the use a diary as described. The
      SMS was derived by adding the VAS for each of these five symptoms.

      The secondary outcome measures included quality of life, reduction of symptoms score, safety
      assessment and monitoring of IgG4. The local reactions were assessed at 30 min after
      injection and measured in cm. The systemic reactions were graded according to EAACI criteria.

      Serum IgG4 measurements The serum concentration of IgG4 against birch alder and hazel pollens
      were determined in blood serum by ELISA tests according Lai et al. before and after the
      three-year SIT.

      Quality of life Patient quality of life was evaluated with the RQLQ score for adults using
      questionnaires every grass pollen season during the study.

      Pollen counts The local grass pollen counts were determined by volumetric pollen trap
      (Burkard, Scientific Ltd, Uxbridge, UK). The peak pollen count was defined as the day with
      highest grass pollen count for each season 3 weeks before and 3 weeks after the peak grass
      pollen count.
    

Intervention name(s): Purethal; Purethal -placebo
Intervention type(s): Drug; Drug
Intervention description(s): prerseasonal course of SCIT - three years; preseasonal course of SCIT - three years
Other intervention name(s): Vaccine
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment