Venom Immunotherapy: From Proteins to Product to Patient Protection.

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil® Bee and Wasp. Venomil® is provided as a freeze-dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister-Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.

SCIT Versus SLIT: Which One Do You Recommend, Doc?

Allergic rhinitis is a prevalent condition that has a significant impact on the quality of life of many patients. When initial therapy fails to control the symptoms, allergen immunotherapy (AIT) has been suggested as an option by the Joint Task Force on Practice Parameters. The 2 main forms of AIT are via subcutaneous and sublingual routes, called subcutaneous immunotherapy and sublingual immunotherapy, respectively. There is debate about which is the better option for patients with each method offering its own pros and cons. We present 2 patients with allergic rhinitisAR that were deemed good candidates for AIT and explore current evidence for both subcutaneous immunotherapy and sublingual immunotherapy. The advantages and disadvantages of each method are discussed with the goal of providing a framework for the physician when deciding on AIT for their patients. In addition, we explore the use of AIT in patients with asthma and atopic dermatitis as potential patient populations that may benefit from the treatment. We use the discussion to provide recommendations regarding which method of AIT is best suited for both our patients.

Phase II/III clinical trial to assess the tolerability and immunological effect of a new updosing phase of dermatophagoides mix–based immunotherapy

Background: Immunologically enhanced subcutaneous specific immunotherapy (SCIT) has been developed with a fast and simplified updosing phase containing equal parts of the house dust mites (HDM) Dermatophagoides pteronyssinus and Dermatophagoides farina ( Dermatophagoides mix) adsorbed on aluminum hydroxide. Objective: To evaluate the tolerability and immunological impact of the updosing phase of this new allergen extract formulation. Material and Methods: We performed a multicenter, open-label, single-arm, phase II/III clinical trial. The inclusion criteria were a clinical history of rhinitis/conjunctivitis due to HDM (with/without asthma) and sensitization to HDM (positive specific IgE and skin prick test). Five updosing injections of Dermatophagoides mix (300, 600, 3000, 6000, and 15 000 SQ+) were administered at weekly intervals with 1 maintenance injection (15 000 SQ+) 2 weeks after the last updosing injection. Two days after each visit, patients were contacted by telephone to follow up on any adverse events. IgE-blocking factor, IgG4, and immediate skin reactivity were evaluated. Results: The sample comprised 102 patients (mean [SD] age, 29.3 [7.7] years; male, 52.9%). There were 117 adverse drug reactions (ADR): 101 were local, regardless of reaction size, in 48 (47.1%) patients and 7 were systemic (all grade I) in 5 (4.9%) patients. All ADRs were mild, except for 1, which was moderate. Six weeks of treatment led to statistically significant increases in IgE-blocking factor and IgG4, as well as a significant reduction in immediate skin reactivity. Conclusion: This new updosing phase of Dermatophagoides mix–based immunotherapy had a good tolerability profile and induced a significant immunological effect (AU)

Antecedentes: Se ha desarrollado una mejorada vacuna de inmunoterapia específica (SCIT) adsorbida en hidróxido de aluminio y administración subcutánea con una fase de incremento de dosis más rápida y simplificada que contiene D. pteronyssinus y D. farinae (HDM; Dermatophagoides mezcla) a partes iguales. Objectivo: Evaluar la tolerabilidad de la fase de incremento de dosis de esta nueva formulación de extracto alergénico en SCIT y su impacto inmunológico. Material y Métodos: Ensayo clínico multicéntrico, abierto, de un brazo, fase II/III. Los sujetos que se podían incluir eran pacientes con una historia clínica de rinitis/conjuntivitis a ácaros de polvo doméstico (con/sin asma) y que presentaran sensibilización a HDM (IgE específica y prueba cutánea positiva). Se administraron cinco dosis semanales de Dermatophagoides mezcla en la fase de inicio (300, 600, 3000, 6000 y 15.000 SQ+) y una inyección de mantenimiento (15.000 SQ+) dos semanas tras la última inyección de la fase de incremento de dosis. Dos días tras cada visita se contactó con los pacientes por teléfono para seguir cualquier acontecimiento adverso (AE). Además, se evaluaron la IgG4, factor bloqueante de IgE y la respuesta cutánea inmediata. Resultados: Se incluyeron 102 sujetos en el ensayo (52,9% varones) con una edad media de 29,3±7,7 años. Se notificaron 117 reacciones adversas (RA) relacionadas con el medicamento en investigación: 101 locales, con independencia del tamaño de la reacción, en 48 (47,1%) pacientes y 7 sistémicas, todas grado I, en 5 (4,9%) pacientes. Todas las RA fueron de intensidad leve, excepto una, de intensidad moderada. Tras seis semanas de tratamiento, se obtuvieron incrementos estadísticamente significativos en el factor bloqueante de IgE y en IgG4, así como en la reducción de la respuesta cutánea inmediata. Conclusión: Esta nueva fase de incremento de dosis con inmunoterapia con Dermatophagoides mezcla presenta un buen perfil de tolerabilidad e induce una respuesta inmunológica significativa (AU)

[The estimation of treatment of Hymenoptera venoms allergy in children]. / Ocena sposobów immunoterapil dzieci uczulonych na jady owadów blonkoskrzydlych.

Specific immunotherapy in patients hypersensitive to Hymenoptera venom is effective method of preventing from severe adverse events after wasp or honey bee sting. In children very often the conventional method was used. In this method injections of vaccines in rising doses was repeated in intervals of 7 days during 3 or 4 months. After obtaining the dose of 100 microg/ml the maintenance therapy is continued during 3-5 years with prolongation of time between vaccine injection to 4-5 weeks. In this paper the "rush" method of immunotherapy was described. Using this method the maintenance dose of vaccine can obtained after 5 days therapy using 3 to 5 concentrations of vaccines during one day. The preliminary effects in 10 children showed that it is safe method and except one children who have the local manifestation of oedema did not observed adverse effects. The efficacy of sting immunotherapy was documented by presentation the 31 cases of children treated by conventional method. The immunotherapy in a short time after "rush" method in our opinion make progress in this treatment.

Regulatory changes that affect coding for immunotherapy.

BACKGROUND: During the past decade, a variety of federal regulations have had a significant impact on the way allergen immunotherapy is reimbursed and how Current Procedural Terminology (CPT) codes are used for this purpose. As mandated by the US Congress, the Centers for Medicare and Medicaid Services (CMS) through the Office of the Inspector General (OIG) targeted immunotherapy codes for scrutiny, because they are some of the most frequently used codes. OBJECTIVE: To examine how federal regulations have affected reimbursement for allergy immunotherapy and other allergy services. METHODS: A review was performed of the OIG survey of allergy immunotherapy and the OIG recommendations on CPT coding compliance guidelines. RESULTS: A preliminary survey found problems with medical appropriateness of allergen immunotherapy. For this reason, the OIG performed a more comprehensive study of 301 physicians using code 95165 to analyze by medical record and billing data whether the new billing rules were being correctly used and found that only 44% of physicians were following the new definition of a billable dose. In the early 1990s, the federal government served notice of its intent to more aggressively identify and prosecute health care providers who improperly billed and collected for medical services. Through the adoption of the 1991 US Sentencing Commission Guidelines, the government sought to enhance compliance by mandating lesser criminal penalties for violating organizations that nevertheless maintained and operated "effective compliance plans." In 2002, the OIG audited health care providers and recouped dollar 14.4 billion in improper payments by Medicare. Between January and June 2003, Medicare excluded 1,241 individual providers and health care entities due to fraudulent billing practices. CONCLUSIONS: Federal regulations have significantly affected reimbursement for allergy immunotherapy and other allergy services. Allergists need to be aware of these changes and implement the new recommendations into their practices.