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Whether Ig engagement by antigen is required to initiate somatic evolution and affinity maturation is not well defined. Silver and colleagues show that germinal center flexibility permits nonspecific B cells to achieve de novo antigen recognition and antibody affinity maturation.

Background Patients with severe asthma often require oral corticosteroid (OCS) treatment. Clinical trials have demonstrated that mepolizumab can reduce OCS dependence, but real-world data are limited. Objective To evaluate the impact of mepolizumab on OCS use, asthma exacerbations, and asthma exacerbation-related costs in a real-world setting. Methods This retrospective cohort study (GSK ID: 209642; HO-19-19597) analyzed data from the MarketScan ® Commercial database (identification period: November 2015–September 2017). Patients were ≥12 years old at mepolizumab initiation (index date), had a baseline asthma diagnosis, and received ≥2 mepolizumab administrations in the first 6 months of follow-up. OCS use, asthma exacerbation rate, and asthma exacerbation-related costs were assessed in the 12-months before (baseline) and 12-months after (follow-up) mepolizumab initiation. Results Mepolizumab was associated with a 14.7% reduction in the proportion of patients with ≥1 OCS claim from baseline to follow-up (93.4% vs 79.7%; P <0.001). The mean numbers of OCS claims/patient and OCS bursts (≥20 mg prednisone equivalents for 3‒28 days) between baseline and follow-up were also reduced by 29.1% ( P <0.001) and 36.8% ( P <0.001), respectively. Reductions in chronic OCS use were demonstrated during follow-up in patients with baseline mean OCS dose ≥5mg and those with a mean OCS dose ≥10mg 90 days before index; the proportion of patients with no OCS use also increased from 6.6% to 20.3% between baseline and follow-up. Conclusion Our findings demonstrate that mepolizumab therapy is associated with reduced OCS use in patients treated in a real-world setting, potentially mitigating adverse health sequelae caused by OCS use in these patients.

Background: Patients with severe asthma frequently have associated comorbidities, which can compound existing symptoms, complicating asthma management. Objective: To describe the real-world effectiveness of mepolizumab in patients with severe asthma stratified by common overlapping comorbidities. Methods: This was a retrospective analysis of patients with asthma from the MarketScan Commercial and Medicare Supplemental Database initiating mepolizumab treatment (index date). Eligible patients had more than or equal to 1 claim (excluding claims for diagnostic tests) with a diagnosis code for more than or equal to 1 of 7 comorbidities (atopic disease, nasal polyps, chronic sinusitis, obesity, respiratory infections, chronic obstructive pulmonary disease, and depression/anxiety) during the 12-month preindex baseline period; these were used to stratify patients into 7 nonmutually exclusive subgroups. Outcomes included asthma exacerbations and exacerbation-related health care resource utilization during the 12-month baseline and follow-up periods. Each patient acted as their own control. Results: Of the 639 patients included, the most common comorbidities were atopic diseases (73.2%), respiratory infections (55.6%), and chronic sinusitis (45.1%). Across all 7 comorbidity subgroups, there were significant (P < .05) reductions of 38% to 55% and 57% to 83% in exacerbations and exacerbations requiring hospitalization, respectively, during the follow-up vs baseline period, except for exacerbations requiring hospitalization in the nasal polyp subgroup, owing to the small subgroup sample size. During the follow-up vs baseline periods, mean number of oral corticosteroids claims was significantly (P < .001) reduced by 29% to 38%; 39% to 47% of patients achieved greater than or equal to 50% oral corticosteroids dose reduction. Significant reductions in exacerbationrelated health care resource utilization were also observed. Conclusion: Mepolizumab treatment provided real-world clinical benefits in patients.

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For decades, intravenous immunoglobulin (IVIg) has provided safe and effective therapy for immunodeficient patients. This proof-of-principle study describes a novel approach to generate personalized IVIg for chronic, antibiotic-resistant infection in real time.