3.6 Symptomatic medication
The use of any symptomatic medication decreased significantly from 96.1% at day 1 of HDM SLIT-tablet treatment to 85.9% at 1 week, 83.0% at 3 months and 75.5% at 1 year of treatment, respectively.
DISCUSSION
In this observational study, safety, tolerability, satisfaction, compliance, and clinical effectiveness were assessed for HDM SLIT treatment in Dutch daily practice. AEs observed are mostly mild to moderate and decrease in frequency with treatment duration, confirming HDM SLIT-tablet safety. Moreover, symptomatic medication uses decrease, and CARAT scores improve with treatment, indicating clinical effectiveness. Thus confirming safety and clinical efficacy previously established in trials. In addition, compliance is high in treatment-persistent patients and both patients and physicians assess treatment to be tolerable and satisfactory.
In this study, 271 (65.3%) patients experienced AEs. Oral allergy reactions (58.6%) were most frequently observed, followed by airway complaints (12.4%), and GI reactions (9.4%). In the phase III trial by Demoly et al. 67% of patients on 12 SQ-HDM experienced AEs comprising: oral pruritis (20%), throat irritation (14%) and mouth oedema (8%); indicating similarity in frequency and location of AEs in clinical trial and in daily-practice setting. The proportion of AEs experienced by patients in real-life is higher than in France (32%) but lower than in Scandinavia (80%). Possible explanations for the observed differences may include differences in study design and environmental factors such as climate and time spend indoors.
CARAT questionnaires were used to monitor treatment as recommended by Dutch guidelines. As the MCID for CARAT is established, significant increases in CARAT scores that are more than the MCID may indicate clinical effectiveness. Therefore, post hoc analyses on changes in mean CARAT scores were conducted. CARAT scores increased significantly and clinically meaningful after 3 months (> 4 points) and 1 year (6 point) treatment compared to baseline. This shows clinical effectiveness and confirms the previously established clinical efficacy.
In real life, patients often do not fill out their prescriptions as advised, while AIT treatment needs to be persisted for 3 years. In the past, major issues were reported with SLIT drops compliance in the Netherlands. Only 7% of patients was found to consistently and timely pick up refills. In the present study, compliance (defined as 80-100% of SLIT-tablets taken daily) was excellent: 96.7% at 1 week, 91.5% at 3 months and 86.6% at 1 year, respectively. This is in line with recent studies. In a Swedish-Danish study SLIT-tablet compliance was 93.2% at 1-year. Moreover, data from the Danish prescription register showed a compliance rate of 53% and 57% for SLIT-tablet and SCIT, respectively, after 3-years treatment. Furthermore, compliance in a recent Dutch grass pollen SLIT-tablet study was 76%. Possible explanations for the observed differences include: increased attention on compliance, the definition of compliance, different study populations, and differences in SLIT type (drops vs tablets).
Ways to improve compliance include more patient visits and selecting patients dedicated to persisting treatment. For example compliance in clinical trials is generally higher than in real-life studies. In addition, solid patient education on SLIT-tablet treatment may help. Part of patient education may be reassuring patients, that AEs will decrease over time as validated by this study. Moreover, if AEs occur, adding symptomatic medication may be considered.
Discontinuation was higher in this real-life study compared to the phase III trial by Demoly et al. 14.5% of patients stopped treatment due to AEs and 18.3% patients stopped because of motivational/other reasons versus 4.1% and 6.6% in the trial, respectively. However, discontinuation was in line with a recent Dutch real-life grass pollen SLIT-tablet study, which reported discontinuation in 9.8% of patients due to AEs and 15.3% because of other reasons. Possible explanations may be the more intensive follow up of patients in trials and variations in patient populations.
Patients and their physicians were asked about satisfaction and tolerability of treatment when they discontinued or completed the study. Responding patients (74.5%) and physicians (80.1%) reported treatment to be well to very-well tolerable. Moreover, most patients (72.8% of responders; 62.4% of all patients) and their physicians (80.0% responders; 69.4% for all patients) were satisfied with treatment. This is in line with previously reported satisfaction for SLIT-tablet therapy.