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- Material and methods
Background: Specific immunotherapy (SIT) is a valuable treatment for respiratory allergy, and the use of chemically modified allergens (allergoids) has improved its safety, as testified by several studies. We evaluated the effects of a SIT course with an allergoid extract of Parietaria pollen in a double-blind, placebo-controlled trial.
Methods: The study was double-blind in the first year; then it was prolonged up to 3 years with all patients on active treatment. Clinical effectiveness, safety, skin reactivity, systemic immunologic parameters, and subjective assessment were evaluated. We also had available a self-evaluation recorded in a follow-up visit 4 years after the discontinuation of SIT.
Results: A significant reduction of the symptoms plus drug intake scores during the pollen seasons was observed in the patients receiving active SIT. The placebo patients, after switching to active SIT, also showed significant clinical improvement. The clinical efficacy persisted during years 2 and 3 of treatment. After year 1, the actively treated patients reported a significant subjective improvement (frequency of symptoms, P=0.001; duration of symptoms, P=0.024; physical performance, P=0.043) compared with the placebo group. The self-evaluation by visual analog scale showed that all patients maintained a significant clinical improvement up to 4 years after discontinuing SIT (year 1: active=+31.6%, placebo=−15.7%; year 7: active=+35.8%, placebo=+31.3%). The systemic immunologic changes after active SIT paralleled those described elsewhere (IgE decreased from 22 to 9 and from 21 to 8 IU/ml; IgG4 increased from 43 to 87 and from 18 to 60 IU/ml). A significant decrease in skin reactivity to three different allergen concentrations was observed at year 3 compared with pretreatment values (P<0.05).
Conclusions: The investigational SIT with Parietaria appeared to be effective and safe; a 3-year course of treatment achieved a long-lasting efficacy.
Allergen-specific immunotherapy (SIT) is presently regarded as an effective therapeutic tool for treating respiratory allergy. Its clinical effectiveness has been proved for allergic rhinitis and asthma in a large number of controlled studies (for review, see Refs. 1–3), and a recent meta-analysis study has confirmed the clinical observations ( 4). SIT acts as a biologic response modifier, and it is now the only treatment able specifically to interfere with the immune response and to modify the natural history of the allergic disease; this fact implies that SIT has to be considered a prophylactic desensitizing treatment rather than a merely symptomatic therapy ( 1).
The use of standardized extracts ( 5) has improved the reliability of SIT and has permitted a batch-to-batch consistency which has improved the safety of the treatment. Two other approaches can be used to minimize the risk of severe adverse events: the first is the noninjective administration of the extract, which is presently considered a promising route ( 6); the second is the use of modified extracts. This latter approach involves the chemical modification of the allergens (by formaldehyde or glutaraldehyde) in order to reduce their allergenicity (i.e., reactivity to specific IgE) yet still maintain the capacity of interacting with the immune system and of interfering with the immunologic response. The chemically modified allergens are commonly called allergoids (7, 8), and several clinical trials supporting their efficacy and safety have been so far performed (9–11). In addition, because of their safety, allergoids usually allow the use of simplified schedules convenient for the allergist. The efficacy of SIT has been confirmed, and several results indicate that the beneficial effects of SIT can be maintained for years after discontinuation (12–14); therefore, this specific issue is currently under investigation.
Parietaria (wall pellitory) is a member of the Urticaceae family widely diffused in Mediterranean areas; its pollination peaks between March and June, but Parietaria can be considered almost a perennial allergen in some regions. Since this plant is a common cause of respiratory allergy in the Mediterranean region, SIT with Parietaria has sometimes been investigated over the last 10 years.
In the present study, we investigated the clinical effectiveness and the safety of allergoid immunotherapy with Parietaria in patients with respiratory allergy. The first year of the study involved a double-blind, placebo-controlled design; this was followed by 2 years of open study. In addition to the clinical evaluation, some paraclinical parameters (skin reactivity, specific Ig) were also monitored, as detailed below. The patients were also followed for up to 4 years after the treatment discontinuation by means of a self-evaluation scale.
- Top of page
- Material and methods
SIT is a valuable tool for the prophylactic treatment of respiratory allergies when it is correctly prescribed and administered (1, 2). Improving the safety of the treatment has long been one of the major aims of the clinical research, and the modified allergens (allergoids) represent a rational approach to improving the safety. Allergoids are chemically modified (by glutaraldehyde or formaldehyde) allergens, which maintain the capacity of modulating the immune response without reacting to the specific IgE. Allergoid preparations have been tested and validated in several controlled trials on allergic patients. In the present randomized clinical trial, we evaluated for up to 3 years the clinical efficacy and some paraclinical effects of allergoid immunotherapy (Purethal™Parietaria, Haarlem Allergen Labs) with Parietaria pollen. The study was kept double-blind and placebo-controlled during year 1; in years 2 and 3, the active treatment was administered to all patients. The clinical effectiveness of the investigational SIT was clearcut: the patients receiving the active treatment showed a significant improvement of the symptom plus drug-intake score. The cumulative score of symptoms plus drug consumption can be considered a reliable global index of clinical improvement, since symptoms and drug intake are strictly dependent on each other.
A significant reduction of the specific IgE levels was observed in all patients after 12 months of active treatment in comparison with the baseline levels. Furthermore, an increase in the allergen-specific IgG4 was also observed, as previously described. In the present experimental conditions, these changes well correlate with the clinical efficacy. Nevertheless, it is not possible to determine whether the Ig modifications are an active part of the mechanism of action of SIT (blocking antibodies theory) or rather represent an epiphenomenon of the allergen administration (16, 17). In any case, the observation confirms that SIT affects the immune response and the specific Ig balance. As far as the skin is concerned, a reduction of the clinical early wheal/flare response has been observed, and it was consistent with the reported detailed observations in the cutaneous model ( 18).
The subjective self-assessment herein performed by a questionnaire globally confirmed the objective clinical measurements. It is important to underline that the perceived improvement refers to the global physical performance, which can be considered an indirect index of the quality of life. Interestingly, the overall self-evaluation by analogic scale showed that the clinical improvement was maintained for up to 4 years in all patients, whether receiving a 3-year or a 2-year course of treatment. Moreover, taking into consideration the intrinsic limits of such a simple self-evaluation, we may assume that the duration of the treatment is critical to the long-lasting effects.
As far as the safety of the treatment is concerned, some reactions, both systemic and local, occurred, but they were not life-threatening and responded to simple management by the allergist. Furthermore, a temporary dose reduction was sufficient to overcome the inconvenience and to achieve the scheduled dose. In conclusion, the herein investigated allergoid SIT with Parietaria pollen was demonstrated to be an effective and safe therapeutic approach for the long-term treatment of respiratory allergy.