Immunotherapy for allergen-related respiratory diseases

Subcutaneous and sublingual immunotherapy (SCIT, SLIT) are the most common methods for controlling allergic rhinitis (AR). At this year's APAAACI Congress, Prof. M. Okano, MD, presented research on the safety, efficacy and adherence of the two treatment regimens.

SCIT and SLIT in everyday clinical practice

Subcutaneous and sublingual immunotherapy (SCIT, SLIT) are the most common methods for controlling allergic rhinitis (AR). At this year's APAAACI Congress, Prof. M. Okano, MD (International University on Health and Welfare School of Medicine, Narita, Japan) presented research on the safety, efficacy and adherence of the two treatment regimens.

A rise in allergic rhinitis

The prevalence of allergic rhinitis has increased in recent years, with 50% of the Japanese population suffering from AR, mainly due to Japanese cedar pollen (JCP) and house dust mite allergens (HDM). Treatment options are mainly SLIT and SCIT. Safety, efficacy and adherence are factors that can influence the choice of treatment.

Safety of immunotherapy

The occurrence of side effects under SLIT and SCIT has been studied many times. Prof. Okano presented several studies dealing with the occurrence of adverse side effects in the context of immunotherapies:

• The incidence of adverse reactions to SCIT was analysed in a cohort of 98 patients. Local reactions were the most common (proportion of subjects affected: 12.2%). Systemic side effects were rare (1% of subjects).
• Several phase 3 studies investigated the safety profile of SLIT. Different antigen doses and forms of administration (tablets, drops) for the therapy of HDM and JCP allergy were compared. A correlation between the concentration of the administered antigens and the side effect rate can be assumed: A low AG dose correlated with fewer negative side effects. However, the severity of the side effects was mild and tolerable. Anaphylaxis was not documented.
• The EMA (European Medicines Agency) analysed the number of anaphylaxis induced by SLIT for HDM allergy from 2016 to 2019. A total of 82 patients suffered anaphylaxis (number of anaphylactic shocks: 6). No fatal reaction was documented. This study suggests that anaphylactic events are rare but present with sublingual immunotherapy.
• Affected individuals whose AR is triggered by both HDM and JCP (polysensitisation) were studied in a multicentre open-label study (n = 109). After initial monotherapy with SLIT against HDM or JCP, subjects were given dual SLIT against both antigens. During the study, 76% of the subjects experienced side effects, of which over 99% were mild concomitant effects. Two subjects had moderate side effects (urticaria, dyspnoea), which led to their withdrawal from the study.

Effectiveness of SLIT and SCIT

The symptom-reducing effect of SCIT and SLIT is the subject of several research papers. Even though the results are not always congruent, SCIT seems to be more likely to lead to therapeutic success than SLIT.

• A meta-analysis (36 randomised controlled trials) compared the effectiveness of SCIT or SLIT (drops and tablets) with grass pollen allergens versus placebo for the treatment of seasonal AR. The study evaluation showed that SCIT achieved significantly better symptom control than SLIT.
• In a comparable research study with the same question (37 randomised controlled trials), the following conclusion was reached: The significantly best symptom reduction in AR could be achieved by therapy with SLIT tablets as well as with SCIT.

• The GRASS clinical trial (n = 106) analysed the effect of two years of immunotherapy with grass pollen antigens in patients with AR. Subjects randomised into 3 arms received SCIT, SLIT or placebo. Study participants on SLIT and SCIT did not differ in quality of life. Symptom control after SCIT exceeded the effect of SLIT in the first year of therapy, and in the second year of treatment both therapy regimens led to comparable results.
• SCIT also seems to be more efficient in the case of allergy to HDM: Based on a meta-analysis of 37 randomised controlled trials, SCIT was convincing with a significantly clearer symptom reduction than SLIT.

Adherence under immunotherapy

In addition to the safety and efficacy of the therapy regime, high adherence is crucial for treatment success. A Dutch retrospective real-life study addressed this aspect of immunotherapy: The study showed that the discontinuation rate under SLIT was significantly higher than under SCIT (1st year of treatment: SLIT 62% vs. SCIT 20%, 3rd year of treatment SLIT 93% vs. SCIT 77%).

In contrast, adherence to SLIT seems to be much higher in Japan. In a Japanese research study, the percentage of discontinuations was only 4% in the first year of treatment and 14% in the third year. Good adherence was also associated with optimised symptom control.

Compliance - a question of patient information?

According to Prof. Okano, one possible reason for the high adherence in Japan could be the national SLIT registration system. After a medical indication has been made, the sufferers must complete several information sessions and tests on the course of treatment before immunotherapy is approved. In addition, much emphasis is placed on patient education regarding SLIT, e.g. with brochures.

Conclusion:

In clinical practice, SLIT is preferable to SCIT, as Prof. Okano emphasised. The advantage here is the good safety profile and the oral application. However, if the patient wants symptom control as quickly as possible and refuses daily treatment, SCIT should be considered. Moreover, training and information material on the understanding of autoimmune therapy are helpful to promote therapy adherence.

Reference:
Okano, Prof. Dr. med. M., International University of Health and Welfare School of Medicine Narita, Japan, Symposium Immune Tolerance and Immunotherapy: SCIT and SLIT for Respiratory Allergic Diseases, Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) 2021 International Conference, 15-17.10.2021.