Background: There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata. Objectives: We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata. Method: We performed a multicenter, randomized, doubleblind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 mg of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG 4 levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria. Results: There were significant reductions in the combined symptom and medication score for the 0.37-mg dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG 4 levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported. Conclusion: Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG 4 levels.

Background Polymerized allergens conjugated to non‐oxidized mannan (PM‐allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM‐allergoids are readily taken up by DCs and induce Treg cells. This first‐in‐human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM‐allergoid (PM‐HDM) administered subcutaneously (SC) or sublingually (SL). Methods In a randomized, double‐blind, double‐dummy, placebo‐controlled trial, 196 subjects received placebo or PM‐HDM at 500, 1000, 3000, or 5000 mannan‐conjugated therapeutic units (mTU)/mL in 9‐arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. Results No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. Conclusions PM‐HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.

Aim: Assessment of safety, tolerability and changes in global clinical impression with an multiallergen immunotherapy treatment without dilutional effect in polyallergic patients. Patients & methods: This observational prospective study included patients with allergic rhinitis-rhinoconjunctivitis with or without asthma between 5 and 60 years old receiving immunotherapy treatment with a mixture of two allergenic sources. All adverse events were recorded. Global clinical impression, tolerability subjective assessment and satisfaction were also assessed. Results: 130 patients were analyzed. Nine clinically relevant local adverse reactions were reported in six patients (4.6%). Six systemic reactions (grades 0–I) occurred in four patients (3.1%). Patients improved significantly in their global clinical impression. Good tolerability subjective assessment and satisfaction values were also observed. Conclusion: This multiallergen immunotherapy treatment without dilutional effect can be considered as a potential therapeutic alternative for polyallergic patients suffering from allergic rhinitis.

Aim: To evaluate tolerability and efficacy of Parietaria judaica subcutaneous immunotherapy on patients with allergic rhinoconjunctivitis. Patients & methods: 51 patients were assigned to build-up scheme (six increasing doses) of P. judaica depot native extract, plus three maintenance monthly administrations. Results: Out of 470 administered doses, only 3.8% elicited systemic reactions (1.5% nonspecific and 2.3% grade I). Concerning the exploratory efficacy parameters: cutaneous reactivity at the final visit versus baseline was significantly decreased; specific titers of IgG and IgG4 increased significantly and patients showed a significant decrease in the rhinitis symptoms score. Conclusion: P. judaica subcutaneous immunotherapy (Allergovac® depot ROXALL Medicina España S.A., Zamudio, Spain) with an abbreviated up-dosing scheme showed an adequate safety and tolerability profile and induced preliminary efficacy changes.

e15643 Background: Skin side effects are common manifestations of antineoplastic drugs that are frequently observed in early clinical trials. Therefore, there is a need to identify skin toxic agents before clinical development in order to predict severe skin manifestations. In many cases, skin toxicity is due to sensitization, a key immunologic process mediating redness, swelling and itching that can lead to more severe skin alterations. Methods: We adapted three skin cellular in vitro techniques for cutaneous drug sensitization assessment of the Organization for Economic Cooperation and Development (OECD, 2012) in order to predict antineoplastic drug skin sensitization: 1) Direct peptide reactivity assay (DPRA) was assessed by high performance liquid chromatography (HPLC) coupled to ultraviolet detector, to detect covalent binding of antineoplastic to skin proteins (haptenation). 2) KeratinoSense skin sensitization assay was evaluated in keratinocyte cell line (HaCaT) transfected with a selectable plasmid to quantify luciferase gene induction by chemiluminescence as a measure of activation of Keap1-Nrf2-antioxidant response element involved in the cellular processes in skin sensitization and 3) The human cell line activation test (h-CLAT) represents the activation of dendritic cells by the increase of CD86 and CD54 surface markers measured by flow cytometry. An antineoplastic was considered sensitizing when at least two of these three tests were positive. Antineoplastic tested were paclitaxel, erlotinib, imatinib, sunitinib, cetuximab, olaparib, palbociclib and everolimus. Results: Paclitaxel was positive for all the three tests; the DPRA formation, keratinoSense activation and h-CLAT expression showing the highest level of sensitization. Moreover sunitinib, and imatinib were positive for two of the three in vitro cellular tests, being considered sensitizing drugs. In contrast, erlotinib, cetuximab, olaparib, palbociclib and everolimus were considered non-sensitizing antineoplastic agents. In the case of erlotinib a high proportion of apoptosis of the keratinocytes during the keratinosense test was observed, suggesting that cutaneous toxicity could be due to cytolysis instead of sensitization. Conclusions: Results obtained in this work suggest that pre-clinical assays may predict skin sensitization and be of potential value to predict skin sensitization of antineoplastic drugs before clinical development. Further assessment with in vivo tests will help to identify the cutaneous toxic mechanisms of those non-sensitizing drugs as cetuximab