A non-stationary Markov model for economic evaluation of grass pollen allergoid immunotherapy.

INTRODUCTION: Allergic rhino-conjunctivitis (ARC) is an IgE-mediated disease that occurs after exposure to indoor or outdoor allergens, or to non-specific triggers. Effective treatment options for seasonal ARC are available, but the economic aspects and burden of these therapies are not of secondary importance, also considered that the prevalence of ARC has been estimated at 23% in Europe. For these reasons, we propose a novel flexible cost-effectiveness analysis (CEA) model, intended to provide healthcare professionals and policymakers with useful information aimed at cost-effective interventions for grass-pollen induced allergic rhino-conjunctivitis (ARC). METHODS: Treatments compared are: 1. no AIT, first-line symptomatic drug-therapy with no allergoid immunotherapy (AIT). 2. SCIT, subcutaneous immunotherapy. 3. SLIT, sublingual immunotherapy. The proposed model is a non-stationary Markovian model, that is flexible enough to reflect those treatment-related problems often encountered in real-life and clinical practice, but that cannot be adequately represented in randomized clinical trials (RCTs). At the same time, we described in detail all the structural elements of the model as well as its input parameters, in order to minimize any issue of transparency and facilitate the reproducibility and circulation of the results among researchers. RESULTS: Using the no AIT strategy as a comparator, and the Incremental Cost Effectiveness Ratio (ICER) as a statistic to summarize the cost-effectiveness of a health care intervention, we could conclude that: SCIT systematically outperforms SLIT, except when a full societal perspective is considered. For example, for T = 9 and a pollen season of 60 days, we have ICER = €16,729 for SCIT vs. ICER = €15,116 for SLIT (in the full societal perspective).For longer pollen seasons or longer follow-up duration the ICER decreases, because each patient experiences a greater clinical benefit over a larger time span, and Quality-adjusted Life Year (QALYs) gained per cycle increase accordingly.Assuming that no clinical benefit is achieved after premature discontinuation, and that at least three years of immunotherapy are required to improve clinical manifestations and perceiving a better quality of life, ICERs become far greater than €30,000.If the immunotherapy is effective only at the peak of the pollen season, the relative ICERs rise sharply. For example, in the scenario where no clinical benefit is present after premature discontinuation of immunotherapy, we have ICER = €74,770 for SCIT vs. ICER = €152,110 for SLIT.The distance between SCIT and SLIT strongly depends on under which model the interventions are meta-analyzed. CONCLUSIONS: Even though there is a considerable evidence that SCIT outperforms SLIT, we could not state that both SCIT and SLIT (or only one of these two) can be considered cost-effective for ARC, as a reliable threshold value for cost-effectiveness set by national regulatory agencies for pharmaceutical products is missing. Moreover, the impact of model input parameters uncertainty on the reliability of our conclusions needs to be investigated further.

Cost-effectiveness of grass pollen allergen immunotherapy in adults.

BACKGROUND: Major scientific societies, such as the EAACI or the AAAAI, do not express any suggestion on which form of allergen immunotherapy (AIT) is to be preferred (subcutaneous immunotherapy, SCIT, vs sublingual immunotherapy, SLIT). This choice could depend on their relative pharmacoeconomic value. OBJECTIVE: To assess the cost-effectiveness of AIT for grass pollen, administered as SCIT or SLIT. METHODS: We created a Markovian Model, to evaluate, in a hypothetical cohort of adult patients suffering from moderate-to-severe rhino-conjunctivitis with or without allergic asthma, the cost-effectiveness of SLIT (tablets, Grazax® and Oralair® ) or SCIT (various currently available products, plus indirect nonmedical costs, such as travel and productivity costs) in addition to pharmacological therapy, assuming a 9-year horizon to capture AIT long-term effects. The incremental cost-effectiveness ratio (ICER) was calculated assuming pharmacological therapy as the reference comparator. RESULTS: In the base case, SCIT was slightly more expensive, but more effective than SLIT, being the most cost-effective option (ICER for SCIT, €11 418; ICER for SLIT, €15 212). ICERs greater than €120 000 for both SCIT and SLIT were demonstrated in a scenario assuming that low treatment persistence rates, which are common in real-life, lead to absence of long-term AIT clinical benefit. Considering indirect nonmedical costs SLIT resulted more cost-effective than SCIT (ICER for SCIT, €17 318; ICER for SLIT, €15 212). CONCLUSION: In daily practice, AIT for grass pollens may be a cost-effective option only in patients with low discontinuation rates. SCIT, which is less affected by this limitation than SLIT, seems the most cost-effective AIT form.

Safety and treatment compliance of subcutaneous immunotherapy: A 30-year retrospective study.

BACKGROUND: Safety and treatment compliance are still considered important shortcomings of subcutaneous immunotherapy (SCIT). OBJECTIVE: To assess the rate of side effects (SE) to SCIT and treatment compliance at a hospital medically supervised facility. METHODS: A retrospective review of patients with allergic rhino-conjunctivitis (ARC) with or without asthma, who received SCIT to mites and pollens from 1988 to 2018, was performed. The information was collected from patient's allergen immunotherapy forms that had been prospectically filled in by expert physicians. RESULTS: Two thousand two hundred patients (50.2% males; mean age 29.4 ±â€¯11.7 years) received 3037 SCIT courses. A total of 91,187 injections were given, with a mean SCIT duration of 2.5 ±â€¯1.9 years. Nine hundred fifty-seven patients (43.5%) were compliant as they completed the minimally required treatment duration of 3 years. A total of 1087 SE (1.2% of all injections; 76.8% local reactions) were reported in 513 patients (23.3%). There were 42 anaphylactic reactions (in 29 patients) during the study period; two of these were severe. Adrenalin was administered only once. No anaphylactic shock was reported. Only 39 patients (1.8%) discontinued SCIT because of SE, the majority of whom (24; 61.5%) because of systemic reactions (urticaria, asthma, anaphylaxis). Parietaria vaccines were the most frequently associated to SE. Female gender, number of vaccines administered (2 vaccine vs. 1 vaccine) and year of SCIT inception (1996-2018 vs. 1988-1995) were independently associated to SE. CONCLUSION: SCIT, although not absolutely free of risk, is safe and well tolerated. There is still room for improvement of treatment compliance.