How Long Will Allergy Patients Take Sublingual Immunotherapy?

How long patients with allergic rhinitis adhere to sublingual immunotherapy (SLIT) appears to vary, but further, more rigorous research is needed, results of a systematic literature review suggest.

Dr Scott P. Commins

“This systematic review found that SLIT was well tolerated,” Scott P. Commins, MD, PhD, associate professor of medicine and pediatrics in the Division of Rheumatology, Allergy, and Immunology at the University of North Carolina School of Medicine, Chapel Hill, told Medscape Medical News.

“But limitations in follow-up and language around adherence limited the conclusions about how many patients followed through and remained on SLIT. Thus, there were wide ranges of adherence,” added Commins, who was not involved in the study.

“The jury is still out on longer-term adherence to SLIT,” he noted by email.

While oral antihistamines, intranasal corticosteroids, and other medications provide symptomatic allergic rhinitis relief, allergen immunotherapy is the only available treatment that modifies the course of the disease, the authors explain in International Forum of Allergy & Rhinology.

Wide Variety in Longer-Term Adherence

SLIT’s safety and efficacy are well established, the authors write. But many of the published clinical trials of SLIT involve monitoring, which may affect patient behavior. So researchers don’t know how many patients continue in real life with SLIT for its prescribed duration of 3-5 years or longer.

To assess SLIT adherence in studies that more closely mimic the treatment in real life, corresponding study author Sandra Y. Lin, MD, University of Wisconsin, Madison, and her colleagues at Johns Hopkins Medicine, Baltimore, Maryland, conducted a systematic review of the literature. They searched the standard medical research databases for real-world studies of SLIT adherence, excluding monitored clinical trials.

The 32 prospective and retrospective studies that met their research criteria comprised 63,683 patients in 13 countries, who ranged in age from 2 to 76 years. Studies were Oxford level of evidence 2b, while Agency for Healthcare Research and Quality quality grades ranged from good quality (12 studies) to fair (20 studies). The researchers found:

  • 26 (81%) studies reported persistence rates — continued therapy without being lost to follow-up — between 7.0% and 88.7%

  • 18 (56%) reported adherence rates — persistence according to prescribed SLIT dose, dosing schedule, and duration — between 9.6% and 97.0%

  • 21 (66%) studies asked 2338 participants why they discontinued SLIT prematurely. In 10 studies, respondents most often reported forgetting doses or being lost to follow-up. Four studies reported treatment-emergent adverse events as the most likely reason. Other common reasons included cost, symptom improvement, and perceived inefficacy

Rates of real-world SLIT persistence and adherence in the studies ranged widely for several reasons and precluded meta-analysis, the authors note. Studies varied greatly in participant characteristics, allergies treated, SLIT regimens, locations, and sample sizes. SLIT regimens varied in allergen numbers, drug forms, dosing schedules, and seasons. Study design and quality, follow-up duration, data collection methods, and statistical reporting, also differed.

  • In 12 studies, 3-year persistence rates ranged from 7% to 59.0%. In four studies, 3-year adherence rates ranged from 9.6% to 49.0%

  • Studies with longer follow-up tended to report lower persistence and adherence rates

Allergen immunotherapy is most commonly administered subcutaneously, but can also be given by sublingual, intralymphatic, epicutaneous, intranasal, and oral routes, the authors note.

“SLIT is generally well-tolerated but less of a first-line therapy in many practices, so having some inconsistent language related to adherence was not unexpected,” Commins said.

“SLIT is gaining popularity for allergen treatment,” he added. “We need to better understand the metrics around how patients follow through with SLIT over the longer term.”

More Rigorous Research Is Needed

Commins hopes the results of this study will lead to better documentation and reporting and more consistent definitions of terms related to SLIT.

“The authors assessed a large number of studies but were limited by the reporting of the studies and by the variability in the definitions of adherence and persistence,” he said. 

“It would be interesting to look at longer-term outcomes and adherence rates with SLIT,” he said. “Compared with subcutaneous immunotherapy, which is planned for 3-to-5 years, we generally think of SLIT as needing a longer time frame to effect immunologic change, due to its lower dose. Thus, lower-dose SLIT should be looked at for 5+ years, in my opinion.”

Commins recommends further, “more rigorous studies utilizing similar, standardized outcomes.”

The authors agree. “When interpreting SLIT adherence data, greater vigilance to such inter-study variations may be necessary,” they write. “Future studies of SLIT adherence may also benefit from following concordant definitions of persistence and adherence in addition to utilizing more uniform reporting metrics such as follow-up duration.”

Int Forum Allergy Rhinol. Published online September 9, 2022. Full text

The authors and Commins report no relevant financial relationships. Funding information was not specified.

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