2016 Section 5 Green Book

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

levels during the

treatment period and for an additional 2 years,

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).

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,

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.

In patients who received SLIT

continuously for 3 years, the clinical benefits persisted for about

7 years.

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.

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.

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.

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

predominant in their locales and how best to use this information

to guide therapy, including the use of SLIT.

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.

HOW DOES SLIT ADHERENCE COMPARE WITH

ADHERENCE TO SCIT OR MEDICATIONS?

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.

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

; 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.

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

manuscript.

J ALLERGY CLIN IMMUNOL

nnn

2015

LI ET AL

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