Page 1271 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 91 Immunotherapy of Allergic Disease 1231

The efficacy of SIT in adult asthma has been assessed in effect on surrogate markers suggests that: (i) current forms
many trials over the last 60 years. The results of these studies of oral immunotherapy (OIT) for food allergy are achieving a
are difficult to interpret, either because poor quality allergen temporary remission; (ii) strategies that are more efficacious
extracts were used or because of poor study design. Many trials against basophil reactivity may offer a more sustained state of
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were not placebo controlled; they were either open or single- tolerance. In parallel, work is ongoing to develop injection SIT
blind studies; and in most cases, only small numbers of patients for fish allergies. 16
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were treated. A 2010 meta-analysis reviewed all of the relevant
papers published between 1954 and 2008. Many of the earlier Comparison of SIT With Other Therapies
trials had methodological flaws, but there are sufficient data The majority of clinical trials of SIT for asthma have compared
for general conclusions to be drawn. Symptom scores improved SIT either with untreated historical controls or with a matched
in the treated groups—it was necessary to treat four patients placebo-treated group. To date, the effectiveness of SIT in asthma
to prevent one from experiencing exacerbation of symptoms, has rarely been compared with conventional management (avoid-
and to treat five to prevent one from needing an increase in ance measures and inhaled or oral antiasthma drugs).
medication. SIT reduced the airways response to inhalation
of specific allergen and also improved nonspecific bronchial Effects of SIT on the Natural History of Allergic Disease
reactivity. In recent years, there has been increasing interest in the possibility
In double-blind placebo-controlled (DBPC) trials in patients that SIT may have disease-modifying or preventive effects. These
with grass pollen asthma, active treatment led to a 60–75% are important not only in their own right as desirable outcomes
reduction in symptom scores compared with placebo-treated but also as factors in the economic evaluation of SIT.
patients. Similar results were found in ragweed allergy with Children often start with a limited range of allergic sensitivities
improved peak flow rates during the pollen season and reduced and progress over time to develop IgE against a wider range of
hay fever symptoms and sensitivity to laboratory challenge with inhaled allergens. Treatment with SIT may limit this tendency
ragweed pollen extracts. However, the associated economic analysis to acquire new sensitizations, although the clinical benefit of
indicated that the cost saving in asthma drugs was less than that this preventive effect is not clear. In the most widely cited study,
in SIT. The value of SIT is thus dependent on its ability to improve children with asthma who were sensitized only to HDM were
symptoms and quality of life rather than to reduce the costs of treated with HDM-SIT. Of the 19 treated children, 10 did not
other medications. develop new sensitizations, whereas all 22 untreated children
In patients with asthma who are sensitive to cats, SIT with acquired new sensitivities, in many cases to more than one new
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standardized aqueous extracts reduces the early asthmatic response allergen. A long-term study of treatment with a grass pollen
to inhaled allergen and attenuates responses to room exposure allergoid has confirmed this observation, with 50% fewer new
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to cats. Interestingly, these studies showed a clear delay in onset sensitizations 12 years after completion of the course of SIT.
of symptoms and an overall reduction in symptoms and peak Similar results have been found in a study of children treated
flow recordings after simulated exposure to cats, but there was with SLIT, in which 3% of SLIT-treated children and 34% of
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no protection against allergen-induced increases in nonspecific control subjects developed new sensitizations within 3 years.
bronchial hyperresponsiveness. Another study of cat SIT for It seems probable that this effect is indirect. In other words,
asthma using a depot preparation found a reduction in both it is unlikely that HDM-SIT directly affects the B cells that
specific and nonspecific bronchial reactivity (to cat extract and recognize cat or grass pollen, but by treating the HDM allergy,
histamine, respectively). There is, however, no hard evidence SIT may reduce inflammation in the nose and hence modify
that SIT is of benefit to treat asthma caused by dog allergy. the likelihood that exposure to other allergens will lead on to
Several DBPC studies have examined the effects of SIT in sensitization.
patients with asthma who are sensitive to HDM. Early studies Each year, a proportion of patients with allergic rhinitis go on
used tyrosine-adsorbed or depot preparations, which yielded to develop asthma. This rate of progression has been estimated
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conflicting results, with reductions in drug requirements in at 5% per annum in college students, but this remains, perhaps
children but no improvement in asthma control in adults. surprisingly, an area of considerable uncertainty. Several long-term
Subsequent studies using more modern extracts have found epidemiological studies are now in progress, under the auspices
beneficial effects on symptoms, antiasthma medication use, and of the International Study of Asthma and Allergies in Childhood
bronchial hyperresponsiveness. (ISAAC), and these should eventually shed light on the rate
of progression at different ages and the extent of regional and
SIT for Food Allergy international variation. It has been suggested that SIT may modify
After several false starts, research has now shown that it is possible the natural history of asthma in children who have allergic
to tolerize patients to food allergens, such as peanut. Arguments rhinitis but have not yet developed asthma. Data to support
continue over what to call this, as the tolerance achieved seems this proposition are limited. In the key study, a group of 205
to be temporary, and patients become fully sensitive again if children aged 6–14 years, without previously diagnosed asthma,
they stop treatment. However, the possibility to render patients were treated with SIT for birch or grass pollen allergy in an
with life-threatening food allergy tolerant of the relevant food open randomized design. Three years after completing treatment,
is a useful step forward. In line with the clinical time course, it 45% of the untreated group had developed asthma, whereas
has been shown that basophil sensitivity is suppressed early during only 26% of the treated group had asthma. These results have
peanut tolerization but returns to baseline when treatment is been sustained out to 7 years after completing therapy. Thus in
stopped. In contrast, in patients undergoing SLIT for aeroallergen terms of number needed to treat, four children had to be treated
sensitivity their basophil reactivity takes longer to drop away to prevent one case of asthma, which makes this an extremely
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after starting treatment, but once achieved, the effect on basophils effective therapy. Similar results have been reported with SLIT:
is sustained for months or years after ceasing SLIT. This differential After 3 years of SLIT, 8 of 45 SLIT-treated children and 18 of 44