Systemic reaction rates with omalizumab, subcutaneous immunotherapy, and combination therapy in children with allergic asthma.

Background: For children with moderate-to-severe persistent allergic asthma, omalizumab is effective. However, it is expensive, and there are no current guidelines for discontinuation. Subcutaneous immunotherapy (SCIT) is the only approach that can provide persistent beneficial effects after treatment is discontinued. However, SCIT is contraindicated in poorly controlled asthma. Therefore, we performed, to our knowledge, the first U.S. study that exclusively compared the safety of omalizumab, SCIT, and combination (omalizumab and SCIT) therapy in children with allergic asthma. Objective: We hypothesize that the systemic reaction (SR) rates in children who receive combination therapy are comparable with omalizumab alone. Methods: We performed a retrospective study of children ages 6-18 years old with allergic asthma who, from July 2010 to June 2017, received SCIT, omalizumab, or combination therapy in our children's allergy clinic. Our primary end point was to determine the SR rate among each of these groups. Results: We reviewed the records of 89 patients: 30 patients with SCIT (1550 injections), 30 patients with omalizumab (729 injections), and 29 patients with combination therapy (954 injections). In the SCIT group, 19 SRs (1.2% of injections) occurred in 10 patients (33%). In the omalizumab group, three SRs (0.4% of injections) occurred in three patients (10%). Similarly, in the combination group, three SRs (0.3% of injections) occurred in three patients (10%). Compared with the SR rate in the SCIT group, both omalizumab and combination groups had significantly lower SR rates (p = 0.045 and p = 0.011, respectively). The SR rates in children who received omalizumab and children who received combination therapy were not statistically different (p = 0.73). Conclusion: Children with moderate-severe persistent allergic asthma who received omalizumab or combination therapy had significantly lower SR rates compared with children with allergic asthma who received SCIT alone. SCIT in children treated with omalizumab was safe and may serve both as an omalizumab-sparing treatment and as a bridge to safely administer SCIT.

Current Status of Potential Therapies for IgE-Mediated Food Allergy.

PURPOSE OF REVIEW: The goal of this review is to provide the reader with an updated summary of published trial data regarding the use of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for treatment of IgE-mediated food allergies. RECENT FINDINGS: Data from phase 2 trials for treatment of peanut allergy with OIT and EPIT reveal an increase in the threshold of reactivity for peanut-allergic children. Compared to EPIT, OIT promotes a greater increase in the threshold of reactivity; however, adverse events are more common with OIT. OIT, EPIT, and SLIT appear to modulate the immune response for some food-allergic individuals. Data regarding utility for treatment of food allergies regardless of modality is limited to few foods, as is investigation into treatment of food-allergic infants, young children, and adults. Future trials are likely to focus on young children, food allergies other than peanut, and treatment of multifood-allergic individuals.

Recurrence of Chronic Urticaria: Incidence and Associated Factors.

BACKGROUND: Chronic urticaria (CU) is urticaria that has been present continuously or intermittently for at least 6 weeks. Although the prevalence and characteristics of CU are well established, little is known about recurrent CU (RCU). OBJECTIVES: We sought to establish a definition, determine the frequency, and evaluate risk factors for RCU. METHODS: A retrospective chart review of adult patients with CU evaluated at the University of Texas Southwestern allergy and immunology clinic was performed. RCU was defined as CU recurring at least 6 months after cessation of controller therapy and resolution of prior CU symptoms. Charts were reviewed for symptom resolution and recurrence, subtypes of CU (idiopathic, physical, and urticarial vasculitis), and medication usage (first-line agents, alternative agents, and steroid dependence). RESULTS: Forty-five of 341 patients (13%) had RCU. The recurrence group had a higher frequency of alternative agent use at 57.8% (n = 26) compared with the nonrecurrence group at 34.8% (n = 103), which was statistically significant (P < .01). The rate of steroid dependence was similar in both groups (13.3% in the recurrence group vs 14.5%) and not statistically significant. Individuals exposed to anti-inflammatory agents, immunosuppressants, and omalizumab had a significantly higher relative risk of recurrence compared with those who only used first-line agents (relative risk [RR] 2.32, P < .01; RR 2.69, P < .01; and RR 2.18, P = .05, respectively). CONCLUSIONS: RCU occurs in approximately 13% of patients with CU in our clinic population. Alternative agent use and antihistamine refractoriness appear to place patients at increased risk for recurrence compared with first-line agent use alone.

Penicillin and Beta-Lactam Hypersensitivity.

Ten percent of patients report penicillin allergy, but more than 90% of these individuals can tolerate penicillins. Skin testing remains the optimal method for evaluation of possible IgE-mediated penicillin allergy and is recommended by professional societies, as the harms for alternative antibiotics include antimicrobial resistance, prolonged hospitalizations, readmissions, and increased costs. Removal of penicillin allergy leads to decreased utilization of broad-spectrum antibiotics, such as fluoroquinolones and vancomycin. There is minimal allergic cross-reactivity between penicillins and cephalosporins. IgE-mediated allergy to cephalosporins is usually side-chain specific and may warrant graded challenge with cephalosporins containing dissimilar R1 or R2 group side chains.

Outcomes of using omalizumab for more than 1 year in refractory chronic urticaria.

BACKGROUND: Because omalizumab was only recently approved for refractory chronic urticaria (CU), there are few studies that have evaluated patients using omalizumab for longer than 1 year. OBJECTIVE: To evaluate omalizumab's effectiveness, its feasibility in weaning, and its safety profile in patients with refractory CU who were on omalizumab for longer than 1 year. METHODS: A retrospective chart review was conducted of adults with well-defined refractory CU in the authors' clinic from October 2005 to January 2015 who responded to omalizumab and who had taken it for longer than 1 year. In addition to baseline characteristics, the duration, course, and adverse effects of omalizumab therapy were analyzed. RESULTS: Eight of 10 patients had complete resolution of symptoms after reaching their optimal regimen and had taken omalizumab for a median duration of 37 months (17-112 months). None of them required uptitration of dosage, an increase in frequency of dosage, or add-on therapy. Five of 8 patients, while being tapered, had recurrence of symptoms requiring the reuse of omalizumab. One successfully discontinued omalizumab, 1 was in the process of being weaned but did not experience a flare, and 1 had not attempted weaning. CONCLUSION: This study from the United States suggests that omalizumab is effective and safe in patients with refractory CU who use omalizumab for longer than 1 year. Periodic attempts at weaning patients with CU from omalizumab should be attempted because there could be a chance of spontaneous remission. This might be difficult because symptoms are likely to recur, but restarting omalizumab in these patients seems effective and safe.

Coordinated regulation of adipose tissue macrophages by cellular and nutritional signals.

The current epidemic of obesity is fueling a global rise in non-communicable diseases, including type 2 diabetes mellitus, atherothrombotic disease, and cancer. Obesity is associated with systemic inflammation, with various fat-derived inflammatory factors being implicated in the pathophysiology of insulin resistance. The infiltration of various types of inflammatory cells into adipose tissue seems to be an important mechanism whereby nutrient excess contributes to systemic insulin resistance. In particular, adipose tissue macrophages are abundant in obese adipose tissue, and may be the source of the majority of fat-derived circulating inflammatory factors. This review examines recent studies exploring mechanisms whereby cellular and nutritional signals mediate macrophage recruitment to adipose tissue and their pro-inflammatory activation.