Efficacy and Safety of Omalizumab (Xolair) for Cholinergic Urticaria in Patients Unresponsive to a Double Dose of Antihistamines: A Randomized Mixed Double-Blind and Open-Label Placebo-Controlled Clinical Trial.

BACKGROUND: Cholinergic urticaria (UCOL) is a highly disabling inducible urticaria triggered by an increase in core body temperature. OBJECTIVE: To explore the safety and efficacy of omalizumab in controlling UCOL. METHODS: We conducted a multicenter randomized mixed double-blind and open-label (first 4 months blinded followed by 8 months open-label) placebo-controlled clinical trial in 22 patients suffering from UCOL who were unresponsive to a double dose of antihistamines. We performed an exercise challenge test during each visit as our main outcome variable. RESULTS: The overall rate of exercise challenge test negative at week 48 was 31.3%, with an average increase in exercise challenge test negative rate of 2.9% points (95% CI, 1.5-4.2) per visit. Statistically significant differences in the negative exercise challenge test rate between the placebo and active intervention groups were not observed during the blinded period (first 4 months of the study). However, from the fourth dose, a progressive improvement was observed. When comparing before and after treatment, statistically significant improvements in all secondary outcome measures were noted after 4 doses (UCOL score: P = .0015; visual analog scale score: P = .0108; days with symptoms: P = .0125) and after 8 doses (UCOL score: P = .0005; chronic urticaria quality of life questionnaire: P = .0105; visual analog scale score: P = .0008; and days with symptoms: P = .0144). In the follow-up visit after the cessation of treatment, the symptoms reappeared, with positive exercise challenge test result and significant increases in all variables. Only 4 of 22 patients remained asymptomatic after 3 months of no treatment. No adverse effects were reported. CONCLUSIONS: This randomized mixed double-blind and open-label placebo-controlled trial showed evidence of the safety and potential efficacy of omalizumab in patients with UCOL.

Optimal duration of allergen immunotherapy in children with dust mite respiratory allergy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) discontinuation data in children remain scarce. OBJECTIVE: We sought for differences in the clinical efficacy of 3 vs. 5 yr of SCIT in children with dust mite respiratory allergy. METHODS: We performed a 5-yr, phase IV prospective study. After the first year, the patients were randomized to 3 (IT3) or 5 yr of treatment (IT5). Efficacy was assessed at 3rd and 5th year by symptom and medication scores and visual analog scales (VAS). Skin tests with common allergens and in vitro assessments were also performed. RESULTS: Eighty-one children (mean age: 9 yr) were randomly assigned to 3 (IT3: 41) or 5 yr (IT5: 40) of immunotherapy. After 3 years, rhinitis global scores decreased in IT3 (44%; p = 0.002) and in IT5 (50%; p = 0.001). Asthma global, symptom and medication scores decreased by 100% in IT3 (p = 0.001) and IT5 (p = 0.001). VAS scores also diminished significantly (IT3: 70%, p = 0.001; IT5: 62.5%; p = 0.001). At 5th year, global rhinitis scores were reduced an additional 30% in IT5 children. Comparisons between both groups did not show differences in rhinitis (p = 0.055), asthma global scores (p = 0.948) or VAS scores at 5th year. Twenty percent of IT5 (p = 0.002) and 7% of IT3 children (p = 0.705) developed new sensitizations. At 5th year, sIgG4 determinations decreased in IT3 without significant variations in IT5. CONCLUSIONS: Three years of SCIT induced significant improvement in children with dust mite respiratory allergy, but a 5-yr course added clinical improvement in rhinitis.

Comparison of conventional and component-resolved diagnostics by two different methods (Advia-Centaur/Microarray-ISAC) in pollen allergy.

BACKGROUND: Component-resolved diagnostics (CRD) has recently been introduced into clinical allergology. OBJECTIVE: The aim of this study was to assess the contribution that this new diagnostic technique makes to conventional diagnosis in patients with pollen allergy, comparing CRD with conventional technologies, and to compare 2 CRD methods, Advia-Centaur and Microarray-ISAC. METHODS: Serum samples from 120 pollen-allergic patients were obtained. Immunoglobulin (Ig) E to total extracts (CAP System) and individual allergens using both CRD methods were determined. RESULTS: The 3 diagnostic methods were in agreement in 62.5% of cases. In 30%, the CRD modified the conventional diagnosis either by detecting new relevant sensitizations (mainly to Olea) or by ruling out clinically irrelevant sensitizations caused by panallergens. The main differences between the 2 CRD methods were the deficiency in the ISAC version we used (ISAC-CRD-89) to detect sensitizations to Salsola and Plantago and that Advia-Centaur did not detect sensitizations to cypress. For all allergens except for Par j 1, a significant association in the frequency of sensitization was seen with the 2 CRD techniques and good agreement when comparing the results of the 2 methods in all cases. Significant correlation was found in the concentration of specific IgE in the 2 techniques for the most prevalent allergens in our setting. The results of the different profilins analyzed using Microarray-ISAC were superimposable although somewhat lower in the case of Phl p 12. CONCLUSIONS: Component-resolved diagnostics modified the conventional diagnosis in 30% of cases. The results from the 2 CRD methods showed good agreement and correlation for most allergens.

Three years of specific immunotherapy may be sufficient in house dust mite respiratory allergy.

BACKGROUND: Specific immunotherapy (SIT) duration for respiratory allergy is currently based on individual decisions. OBJECTIVE: To evaluate the differences in clinical efficacy of SIT as a result of the duration between the current recommended limits (3-5 years). METHODS: A 5-year prospective, controlled clinical trial of SIT blind until the first year and randomization to a 3-year (IT3) or 5-year (IT5) course was conducted. Of the 239 patients with respiratory allergy caused by D pteronyssinus initially included, 142 completed 3 years of SIT with good compliance. Twenty-seven controls were included at the third year. Efficacy of SIT after 3 (T3) and 5 (T5) years was assessed by using clinical scores, visual analog scales (VASs), rhinitis (RQLQ) and asthma (AQLQ) quality of life questionnaires, skin tests, and serum immunoglobulins. RESULTS: At T3, significant reductions were observed in rhinitis (44% in IT3 and 50% in IT5; P < .001), asthma (80.9 % in IT3 and 70.9% in IT5; P < .001) scores, VAS (P < .001 in both), RQLQ (P < .001 in both) and AQLQ (P < .001 in both). At T5, the clinical benefit was maintained in both groups, and IT5 patients presented additional decreases (19%; P = .019) in rhinitis scores. At Tf, specific IgG(4) measurements were lower in IT3 (P = .03) without detecting differences in IT5. An increase in asthma score of 133% was the only difference observed in controls. CONCLUSION: Clinical improvement is obtained with 3 years of D pteronyssinus SIT. Two additional years of SIT add clinical benefit in rhinitis only.

Assessment of short-term changes induced by a Dermatophagoides pteronyssinus extract on asthmatic patients. Randomised, double-blind, placebo-controlled trial.

BACKGROUND: Once the optimal dose is reached, subcutaneous immunotherapy [SCIT] with mite extract is capable of reducing symptoms and the need for rescue medication. OBJECTIVE: To assess the capacity of a subcutaneous extract of mites [D. pteronyssinus] to bring about a reduction in concomitant medication as well as in vivo and in vitro changes in just 2-3 months of treatment in patients with allergic asthma. METHODS: A total of 45 patients with persistent mild-moderate allergic asthma due to sensitisation to D. pteronyssinus were included in a multi-centre, double-blind, placebo-controlled trial. Length of treatment was 4 months. After a period for adjusting medication in order to classify asthma severity appropriately, patients were commenced on treatment of 400 or 800 g/day of budesonide as concomitant medication. RESULTS: After 4 months of treatment there were no significant changes in the budesonide dose between the active group and the placebo group. In the active group there was a significant difference between active and placebo group in sIgG4 [p=.0003], as well as a significant increase in the cutaneous tolerance index [2.81, CI 95%: 1.29 - 7.48, which was significant with a Confidence Interval of 95%]. These changes were not observed in the placebo group. CONCLUSION: After just 4 months of treatment, SCIT was capable of inducing in vivo and in vitro changes, but these changes were not reflected in improved clinical outcome within the first 4 months of therapy.

Double-blind, placebo-controlled study of Alternaria alternata immunotherapy: clinical efficacy and safety.

Allergen-specific immunotherapy (ASIT) with fungal extracts has been beset by safety and efficacy problems, which result mainly from qualitative and quantitative variations. Little has been published on the safety and efficacy of these extracts. The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract. A total of 28 patients were selected with rhinitis and/or bronchial asthma because of Alternaria allergy and monosensitization to molds. The patients were randomized to an active ASIT or placebo group, both groups on a conventional immunotherapy schedule (increasing weekly doses until maintenance dose and then monthly doses). Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system. Clinical efficacy was analyzed for a year with symptom/medication diary cards, peak expiratory flow (PEF) measures, clinical severity score, severity of symptoms (visual analog scale), subjective evaluation of treatment by the patient and the physician, and a quality of life questionnaire. Twenty-three patients completed the study; all reached the established maintenance dose with only two mild adverse reactions in the whole sample. Significant improvements were found after 6 months in respiratory symptoms in the active treatment group, and in all symptoms in both groups. PEF increased significantly in the active treatment group but not in the placebo group. The severity of asthma decreased in the active treatment group, and the severity of rhinitis decreased in both groups. Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group, but only after 12 months in the placebo group. Physicians judged the disease course as significantly better in the active treatment group. ASIT with the A. alternata extract was safe, with clinical improvements after one year of treatment.

Double-blind comparative study of cluster and conventional immunotherapy schedules with Dermatophagoides pteronyssinus.

BACKGROUND: The conventional schedule for subcutaneous immunotherapy with allergen extracts, although efficacious and safe, is slow during the dose-increase phase. OBJECTIVE: We sought to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized extract given in a 6-week cluster period and a conventional 12-week schedule during the incremental-dose phase. METHODS: Of 239 patients with rhinitis, allergic bronchial asthma, or both caused by D pteronyssinus , 120 were randomly assigned to the cluster schedule, and 119 were randomly assigned to the conventional schedule. A biologically standardized D pteronyssinus depot extract (ALK-Abelló S.A., Madrid, Spain) was administered in a placebo-controlled, double-blind fashion during the initial phase of cluster or conventional treatment. We recorded adverse reactions, clinical efficacy, cutaneous reactivity, and serum specific immunoglobulins to D pteronyssinus before immunotherapy, when the maximum dose was reached in the cluster and conventional schedules, and after 1 year of treatment. RESULTS: The cluster schedule reduced the time to maintenance dose by 46% and caused systemic adverse reactions (all mild) after only 0.15% of injections, with no differences in comparison with the conventional schedule. Cluster immunotherapy led to decreases in asthma and rhinitis symptoms, reduced the cutaneous reactivity, and produced the increase in specific IgE and IgG 4 levels on reaching the maintenance dose in the sixth week, 6 weeks earlier than with the conventional schedule. CONCLUSION: The cluster schedule for the initial phase of immunotherapy with incremental doses of D pteronyssinus is a safe alternative to conventional immunotherapy and offers the further advantage of achieving clinical and immunologic improvements sooner.