2016 Section 5 Green Book

LI ET AL

J ALLERGY CLIN IMMUNOL nnn 2015

predominant in their locales and how best to use this information to guide therapy, including the use of SLIT.

ARE THERE LONG-TERM BENEFITS TO SLIT? Studies show that the clinical benefits of SLIT can continue after treatment is discontinued. 28,31,54,55 Randomized, double- blind, placebo-controlled trials with grass SLIT showed that after 3 years of active treatment, both clinical and immunologic benefits were demonstrated for at least 2 subsequent years. 28,37 The pivotal trials leading to US approval of timothy tablets showed that 3 years of continuous treatment resulted in a sustained increase in antigen-specific IgG 4 levels during the treatment period and for an additional 2 years, 28 and the PI for the timothy tablets states that ‘‘for sustained effectiveness for one grass pollen season after cessation of treatment, [the product] may be taken daily for three consecutive years’’ (‘‘continuous’’ regimen). 2 Although data from 5-grass tablet clinical trials also showed sustained clinical benefits for at least 2 more years after a 3-year of preseasonal/coseasonal therapy course, 55 the FDA did not give the product an indication for sustained use. No data on the sustained effectiveness of the ragweed product are available. A prospective, open, controlled 15-year study of patients with respiratory allergy who were monosensitized to mites evaluated the duration of SLIT efficacy after discontinuation in relationship to treatment duration. 54 In patients who received SLIT continuously for 3 years, the clinical benefits persisted for about 7 years. 54 In those receiving SLIT for 4 or 5 years, the clinical benefits persisted for 8 years. New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT for 3, 4 to 5, and 15 years (21%, 12%, and 11%, respectively). With respect to children, for whom allergic rhinitis is a risk factor for asthma, the evidence suggests that SLIT might decrease the development of future asthma. For example, an open study of 113 children aged 5 to 14 years with grass pollinosis found the development of asthma after 3 years was 3 times more frequent in the control subjects compared with those who received SLIT. 56 SLIT also was associated with less medication use in the second and third years of therapy, and symptom scores tended to be lower. In an open randomized study of 216 children with allergic rhinitis, SLIT treatment was associated with a significant reduction in new allergen sensitization and onset of persistent asthma. 57 Data from double-blind, placebo-controlled studies on these preventive effects of SLIT are not available yet, but one large trial has been initiated in Europe. 58 ARE THERE DIFFERENCES BETWEEN THE TIMOTHY AND 5-GRASS SUBLINGUAL TABLETS? There are no discernible differences in efficacy or safety between the timothy and 5-grass (sweet vernal, orchard, perennial rye, timothy, and Kentucky bluegrass) tablets in treating adults sensitized to grass pollen during the grass pollen season. Sustained efficacy for up to 2 years has been demonstrated for both, although only the timothy product has FDA approval for sustained benefits. However, no comparative studies between the US-approved grass SLIT products have been done. See Table I for specific dosing and regimens for the timothy, 5-grass, and ragweed products. Ragweed, timothy, and other grasses are prevalent in different regions during specific months. It is the prescribing physician’s obligation to know what pollens and aeroallergens are

WHERE DOES SLIT FIT AMONG ALL MANAGEMENT OPTIONS FOR ALLERGIC RHINITIS?

The management of allergic rhinitis is highly individualized. No single treatment program will be right for all patients. As with other chronic diseases, response to treatment, experience with adverse effects, cost, access, and patient preference are all relevant to management decisions. Unique features of the management of allergic disease include exposure history and patient-specific/allergen-specific sensitization. The optimal management of allergic rhinitis should integrate all these factors through shared (patient-physician) decision making. A detailed allergy history, allergy testing, and physician-patient discussion of management options are essential. Allergen avoidance is often included in the management plan, but complete avoidance is rarely feasible, and clinical effectiveness is variable. Pharmacologic options include antihistamines (oral and intranasal), intranasal corticosteroids, and leukotriene modifiers. When effective and well tolerated, these agents can be considered first-line options. However, they are not effective for all patients, might generate unacceptable adverse effects, and do not have disease-modifying properties. SLIT might be an appropriate first-line treatment when a disease- modifying approach is preferred or for patients who value the potential benefits of immunotherapy (eg, long-term immunomodulation), as well as for those for whom standard drug therapy is ineffective or poorly tolerated. If symptoms are not reduced within 2 years, the patient should be re-evaluated. Those who respond can expect benefits to last up to 2 years after treatment. The safety and efficacy of various SLIT formulations has been demonstrated in 85 randomized, double-blind, placebo- controlled trials published through April 2015. 30,32,33,45,54,59-63 SLIT might be a suitable therapeutic option when a patient pre- sents with a single clinically relevant sensitization (eg, grass or ragweed), when AIT administration outside the physician’s office is preferred, and when the lower risk of anaphylaxis is valued. Generally, patients can expect a reduction in symptoms and concomitant medication over time, as well as improved quality of life during the peak allergy season. Adherence to both SLIT and SCIT outside of double-blind, placebo-controlled trials has been shown to be relatively poor, and adherence rates with SLIT are in line with those for most self-administered treatments for other chronic diseases. 64 Strategies that can enhance SLITadherence include appropriately educating patients about their illness and treatment; discussing goals and expectations 65,66 with a view toward shared decision-making 67 ; follow-up telephone calls, letters, and visits 66,68 ; and text messages and other forms of electronic re- minders. A general reminder at the beginning of the allergy season could also be helpful. HOW DOES SLIT ADHERENCE COMPARE WITH ADHERENCE TO SCIT OR MEDICATIONS?

We thank Ms Marilynn Larkin for her assistance in the preparation of this manuscript.

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