Intradermal Grass Pollen Allergen Immunotherapy for Seasonal Allergy: A Randomized Controlled Trial (original) (raw)
Related papers
Journal of Allergy and Clinical Immunology, 2017
Background: Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous latephase responses comparably with conventional subcutaneous and sublingual immunotherapy. Objective: We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. Methods: We randomly assigned 93 adults with grass polleninduced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment. Results: There was no significant difference in the primary end point between treatment arms (active, n 5 46; control, n 5 47; median difference, 14; 95% CI, 2172.5 to 215.1; P 5 .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P 5 .03) and visual analog scale (median difference, 53; 95% CI, 211.6 to 125.2; P 5 .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense-specific IgE levels (P 5 .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the T H 2 surface marker CRTH2 (P 5 .04) and lower expression of the T H 1 marker CXCR3 (P 5 .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P 5 .03). Conclusion: Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms. (J Allergy Clin Immunol 2016;nnn:nnn-nnn.)
Efficacy and Mechanism Evaluation
BackgroundWe previously reported that repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses, comparable with conventional high-dose subcutaneous and sublingual immunotherapy.ObjectiveTo evaluate the efficacy and mechanism of grass pollen intradermal immunotherapy for treatment of allergic rhinitis.DesignA Phase II, double-blind, randomised controlled parallel-group trial.SettingSingle-centre UK study.ParticipantsAdults aged 18–65 years, with grass pollen-induced allergic rhinoconjunctivitis.InterventionsSeven 2-weekly intradermal injections were given into the forearm, containing eitherPhleum pratensesoluble grass pollen extract (7 ng of the major allergen Phl p 5) or histamine control.Main outcome measuresThe primary outcome was a combined symptom and medication score (CSMS) during the 2013 grass pollen season. Secondary clinical outcomes were overall symptom scores; individual symptoms scores for nose, mouth, eyes ...
Journal of Allergy and Clinical Immunology, 2014
We previously optimised grass pollen nasal allergen challenge and measurement of Th2 cytokines in nasal fluid (Scadding et al, J Immunol Methods 2012;384:25-32). Here we test the utility of this methodology as surrogate for clinical response to immunotherapy. METHODS: In a cross-sectional study we compared 14 grass pollen allergics, 14 non-atopic controls, 14 patients receiving grass pollen immunotherapy, and 4 having completed immunotherapy. Participants underwent nasal challenge and recorded symptoms and peak nasal inspiratory flow (PNIF) to 8 hours. Nasal fluid was collected using absorptive sponges and analysed for Th2 cytokines/chemokines by multiplex assays. Intradermal skin tests were recorded and participants completed retrospective seasonal symptom scores. Clinical and laboratory measurements were performed blind to clinical status of subjects. RESULTS: Participants receiving immunotherapy had reduced nasal symptoms (45% lower combined early and late phase scores, p50.04) and higher PNIF (54%, p50.02) following challenge compared to untreated allergics; they had reduced early (15 minutes, 27% lower, p50.0007) and late (8 hours, 51% lower, p<0.0001) skin responses and seasonal symptom scores (60% less, p50.003). Skin late response and nasal challenge scores correlated with seasonal symptoms (r50.61, p<0.001; r50.45, p50.012). Nasal fluid levels of IL-4,-5,-9,-13, and eotaxin peaked at 6-8 hours postchallenge in untreated allergics (all p<0.001 versus non-atopics at 8 hours). All five were lower in immunotherapy-treated participants, significant for IL-4,-9, and eotaxin at 8 hours (all p<0.05). CONCLUSIONS: Grass pollen nasal allergen challenge represents a useful clinical surrogate and adjunct for assessing clinical outcome of allergen immunotherapy.
Allergy, 2015
Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study. We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n=14) compared with immunotherapy-treated allergics (n=14), plus a non-atopic control group (n=14). Volunteers underwent a standardised NAC with 2,000 BU Timothy grass allergen (equivalent to 1.3μg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. Immunotherapy-treated patients had lower symptom scores (p=0.04) and higher PNIF (p=0.02) after challenge tha...
Clinical and translational allergy, 2013
Subcutaneous immunotherapy with high dose grass pollen (typically microgram quantities) was first described over 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. We previously reported that repeated 2-weekly intradermal injections of grass pollen - containing approximately 7 ng of major allergen Phl p 5 - led to a progressive suppression of the allergen-induced cutaneous response, and that by the sixth injection, this was inhibited by over 90%. The purpose of this trial is to investigate the clinical efficacy of intradermal desensitisation with low doses (i.e. nanogram quantities) of grass pollen allergen for seasonal allergic rhinitis. The Pollen Low dose Intradermal therapy Evaluation (PollenLITE) is a single centre double-blind randomised parallel group controlled trial of the efficacy and safety of intradermal grass pollen injections plus standard treatment, versus histamine injections plus standard treat...
JAMA, 2017
Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunothera...
Safety of Subcutaneous Specific Immunotherapy with Pollen Allergen Extracts for Respiratory Allergy
International Archives of Allergy and Immunology, 2003
Background: Specific immunotherapy (SIT) is a well-documented treatment for respiratory allergy. However, the major risk of SIT is the development of systemic anaphylactic reactions. Objectives: To evaluate the safety of SIT given by subcutaneous route for 3 years to patients with seasonal allergic rhinitis (AR) with or without asthma. Methods: A prospective open-label study of immunotherapy (Chenopodium album, Bermuda grass, or both) in 181 consecutive patients with AR with or without asthma. After an initial dose-escalation phase, a maintenance dose of 0.5 ml of 100,000 PNU/ml was administered monthly for 3 years. The occurrence and severity of systemic reaction (SR) and local reaction was recorded and graded according to the WHO position paper. Results: Of 181 patients enrolled, 57 (31%) did not complete the study (53 due to poor compliance and 4 due to systemic side effects). All 4 patients who developed SR had asthma and all the SR occurred during the doseescalation phase. Three patients had moderate SR (grade 2), while 1 patient had severe reaction (grade 3). Three of the SR occurred within the first 20 min after injection and 1 SR occurred 2 h after injection. None of the reactions were life threatening and were managed easily. Total rhinitis symptom score decreased from 11.8 at baseline to 7.46 at the end of treatment (p ! 0.001). The size of the skin prick test reaction to the main sensitising allergen was reduced from 7.48 B 2.26 mm at baseline to 5.60 B 2.18 mm at the end of treatment, p ! 001. Conclusion: If a strict protocol is used, SIT is safe in AR patients with or without mild asthma and may result in significant subjective and objective improvement.
Journal of Clinical Investigation, 1993
We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a doubleblind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Thl-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance.
When Allergen Immunotherapy Perfectly Meets its Need: A Case Report
Journal of Allergy & Therapy, 2017
Seasonal, pollen-induced allergic rhinitis can be managed by symptomatic drug treatment, but only allergen immunotherapy (AIT) is able to work on the causes of allergy. Usually, the effectiveness of AIT is assessed by clinical criteria, though the ideal outcome is to lose the allergic sensitization to the administered allergen(s). Here we report the case of a patient who after three years of AIT using a grass pollen extract containing Phleum pratense, Dactilys glomerata, Anthoxanthum odoratum, Poa pratensis and Lolium perenne but not Cynodon dactylon, to which the patient was also sensitized, developed a negative response to allergy tests to the administered allergens. After 3 years of SCIT, the patient was free of both nose and lung symptoms during the grass pollen season and had negative results to the pollens included in the extract, while C. dactylon showed a decrease in respect to basal value but not a negative result. The findings from this case show that AIT in optimal circumstances is able to achieve a complete tolerance to the administered allergen demonstrated by the development of negative results to the grass pollens contained in the extract used for the treatment. This confirms the recent definition of AIT as a treatment fulfilling the requirements of precision medicine.
Annals of Medicine, 2011
Purpose of review Allergic rhinitis is a highly prevalent inflammatory disease affecting 20-40% of the children worldwide. Allergen-specific immunotherapy (SIT) is an effective treatment for allergic rhinitis. This article reviews the recent advances in SIT for children. Recent findings In current clinical practice, immunotherapy is delivered as either subcutaneous immunotherapy or sublingual immunotherapy (SLIT). Most meta-analyses and reviews concluded a trend that subcutaneous immunotherapy was better than SLIT in reducing symptoms of allergic rhinitis and rescue medication use, however, SLIT has a better safety profile than subcutaneous immunotherapy. Additionally, the absence of pain on administration of therapy is a character of SLIT, which is well suited for children. T regulatory cells, especially Tr1 cells that secrete interleukin-10 and induce production of immunoglobulin G4, play a role during SIT.