The MaDo real-life study of dose adjustment of allergen immunotherapy liquid formulations in an indication of respiratory allergic disease: Reasons, practices, and outcomes

Abstract

Sublingual allergen immunotherapy (SLIT) is a safe, effective, disease-modifying treatment for moderate-to-severe respiratory allergies. The function and responsiveness of the immune system components underlying the effects of allergen immunotherapy may vary from one patient to another. Furthermore, the severity of the symptoms of allergic disease can fluctuate over time, due to changes in environmental allergen exposure, effector cell responsiveness, and cell signaling. Hence, the allergen dose provided through SLIT can be fine-tuned to establish an optimal balance between effectiveness and tolerability. The objective of the MaDo study was to describe and understand dose adjustments of SLIT liquid formulations in France. We performed a retrospective, observational, cross-sectional, real-life study of allergists and other specialist physicians. Physicians described their patients via an anonymous case report form (CRF). The main patient inclusion criteria were age 5 years or over, at least one physician-confirmed IgE-driven respiratory allergy, and treatment for at least 2 years with one or more SLIT liquid preparations. A nationally representative sample of 33 specialist physicians participated in the study. The physicians' main stated reasons for dose adjustment were adverse events (according to 90.9% of the physicians), treatment effectiveness (60.6%), sensitivity to the allergen (42.4%) and other characteristics (30.3%: mainly symptom severity, type of allergen, and asthma). 392 CRFs (mean ± standard deviation patient age: 27.8 ± 17.5; under-18s: 42.1%; polyallergy: 30.9%) were analyzed. Respectively 53.6%, 25.8%, 15.3%, and 8.7% of the patients received house dust mite, grass pollen, birch pollen and cypress pollen SLIT. Dose adjustments were noted in 258 (65.8%) patients (at the start of the maintenance phase for 101 patients (39.2%) and later for 247 (95.7%)). Dose adjustment was not linked to sex, age, or the number of allergens administered. All measures of disease severity (including symptom severity noted on a 0-to-10 visual analogue scale by the physician) decreased significantly during SLIT. Notably, the mean AR symptom severity score decreased to a clinically relevant extent from 7.6 at SLIT initiation to 2.4 at last follow-up, and the mean asthma symptom severity score decreased from 5.0 to 1.3. The few differences in effectiveness between patients with vs. without dose adjustment were not major. For about one patient in five, a specialist physician decided to reduce or increase the SLIT liquid dose at the start of maintenance treatment and/or during maintenance treatment. This decision was influenced by a broad range of patient and treatment factors, mainly to improve tolerability to treatment and/or enhance effectiveness. In France, dose adjustment of SLIT liquid preparations as a function of the patient profile and/or treatment response is anchored in clinical practice. Precision dosing might optimize the overall benefit-risk profile of AIT for individual patients throughout their entire treatment course, enabling them to achieve both short- and long-term treatment goals, whilst maximizing the safety and tolerability.

Respiratory allergic diseases and allergen immunotherapy: A French patient survey before and during the COVID-19 pandemic

“…In current practice, dose adaptation appears to be common to enable patients to benefit from treatment, whilst maximizing safety and tolerability, as recently evidenced in the MaDo study in France. 33 In this study, dose adjustments were noted in 65.8% of patients, and for 95.7% of them during the maintenance phase (up and down to a similar extent). The main reasons were a wish for greater efficacy (for dose increase), occurrence of adverse effects, worsening of symptoms (for dose reductions).…”

IR (index of reactivity)-house dust mite sublingual immunotherapy liquid formulation for allergic rhinoconjunctivitis: Systematic review and meta-analysis of randomized and nonrandomized studies

“…This may be an advantage of this formulation over AIT fixed-dose SLIT formulations, as recently shown. 53 …”

Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy

“…As preliminary elements, some differences were confirmed in a retrospective observational study involving allergy physicians in France [ 6 ]. In their clinical practice, nearly 80% of physicians reported adapting the dose of AIT downwards or upwards (from rarely to often) in 20% of their patients at the end of the titration phase.…”