Martin Penagos

Summary: Compared to placebo, Dupilumab and Stapokibart (CM310) demonstrate the most significant therapeutic efficacy in treating CRSwNP. All biologics demonstrated favourable safety profiles, with Dupilumab exhibiting the lowest risk of adverse events.

Purpose of the Review: To analyse the evidence regarding the optimal duration of subcutaneous and sublingual immunotherapies to induce long-lasting benefits after treatment cessation for allergic rhinitis and asthma and to identify unmet needs. Recent Findings: Subcutaneous and sublingual immunotherapies are highly effective in desensitising selected subjects with allergic rhinitis and allergic asthma. Double-blind, placebo-controlled, randomised clinical trials of both routes of immunotherapy support international guidelines that recommend their use for at least three years to achieve disease modification and continued clinical and immunological tolerance for allergic rhinitis. Evidence of the long-term effects of allergen immunotherapy in the context of randomised controlled trials for allergic asthma as opposed to rhinitis is limited. Nonetheless, real-world studies suggest the long-lasting benefits of allergen immunotherapy for allergic asthma, as this reduces prescriptions for pharmacotherapy and decreases the risk of asthma exacerbations and hospitalisations. The GINA guideline 2023 recommends the use of house dust mite sublingual immunotherapy as an add-on therapy in subjects with suboptimally controlled asthma, despite the use of low to high doses of inhaled corticosteroids, provided that the FEV₁ is > 70% predicted. Summary: Robust clinical trials of subcutaneous and sublingual immunotherapies have shown that 3 years of continuous treatment modifies the underlying course of allergic rhinitis with long-lasting clinical effects years after withdrawal. Further evaluations of the long-lasting effects of novel routes of allergen immunotherapy for allergic rhinitis and long-term studies for allergic asthma are needed in the context of randomised clinical trials.

Allergen-specific immunotherapy for inhalant allergies, using allergen extracts of proven value, is highly effective in selected patients with allergic rhinoconjunctivitis and allergic asthma. Both subcutaneous and sublingual immunotherapy (SLIT) have been shown to modify the underlying cause of the disease, with long-term clinical benefits that persist for years after their discontinuation. Real-world studies have confirmed the long-term efficacy of allergen immunotherapy in allergic rhinitis (AR) and asthma and shown a reduction in the incidence of lower respiratory tract infections. Sublingual house dust mite (HDM) immunotherapy has been suggested to improve innate antiviral immunity—a likely explanation for this finding. Based on robust randomized controlled trials, the Global Initiative for Asthma (GINA) guideline has incorporated the use of SILT for the treatment of adults with HDM-driven asthma and concomitant AR, with sub-optimal control, regardless of the use of low-to-high doses of inhaled corticosteroids, as long as the patient’s forced expiratory volume in 1 second (FEV1) is > 70%.

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost‐effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis.Methods: We searched nine international biomedical databases for published, in‐progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost‐effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random‐effects meta‐analyses.Results: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD −0.53, 95% CI −0.63, −0.42), medication (SMD −0.37, 95% CI −0.49, −0.26), and combined symptom and medication (SMD −0.49, 95% CI −0.69, −0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post‐discontinuation of AIT, suggesting a benefit in relation to symptom scores.Conclusions: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.

Quiz Ref ID The prevalence of allergic rhinitis in the United States has been estimated at 15% based on physician diagnosis and at 30% based on self-reported nasal symptoms.^1,2 Rhinitis has major effects on quality of life, sleep, and work and school performance.³ Whereas antihistamines and topical nasal corticosteroids are effective,⁴ community surveys suggest that approximately 60% of patients with allergic rhinitis do not respond adequately to these measures.¹ When avoidance of allergens is not feasible and patients have inadequate response to antiallergic medications or have bothersome adverse effects, allergen immunotherapy is a reasonable choice for treatment.⁵ Subcutaneous immunotherapy is highly effective.^5,6 The sublingual route has emerged as an alternative treatment for seasonal allergic rhinitis.^7,8 Three years of continuous treatment with immunotherapy via either delivery method modifies the underlying course of the disease with long-term remission of symptoms for several years after stopping treatment.^9-11 It is unknown whether a shorter course of immunotherapy provides long-term benefits, while reducing overall costs, patient inconvenience, and adverse events.

Background: There is a need to establish the effectiveness, cost‐effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease.Methods: Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random‐effects meta‐analyses.Results: A total of 32 studies satisfied the inclusion criteria. Overall, meta‐analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04–2.09) and no randomized controlled evidence was found in relation to its longer‐term effects for this outcome. There was, however, a reduction in the short‐term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30–0.54), with this finding being robust to a pre‐specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31–1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24–2.18. There was no clear evidence of any longer‐term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08–2.77. AIT appeared to have an acceptable side effect profile.Conclusions: AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short‐term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost‐effectiveness of AIT.

Rationale Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. Objective To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross‐sectional study. Methods We studied nasal and cutaneous responses in untreated subjects with seasonal grass‐pollen allergic rhinitis (n = 14) compared with immunotherapy‐treated allergics (n = 14), plus a nonatopic control group (n = 14). Volunteers underwent a standardized NAC with 2000 biological units of timothy grass allergen (equivalent to 1.3 μg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. Results Immunotherapy‐treated patients had lower symptom scores (P = 0.04) and higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective seasonal symptom scores (P < 0.0001). Compared to untreated allergics, immunotherapy‐treated patients had reduced nasal fluid concentrations of IL‐4, IL‐9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison), and trends for reduced IL‐13 (P = 0.07, area under the curve) and early‐phase tryptase levels (P = 0.06). Conclusions Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.