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In recent years, major developments have occurred in severe asthma management. Different asthma phenotypes and subgroups have been identified and new treatment options have become available. A total of five monoclonal antibodies are currently approved in severe asthma treatment: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. These drugs have been shown to reduce exacerbations and to have an oral corticosteroid-sparing effect in many severe asthma patients. However, biological treatment is not successful in all patients and should be discontinued in non-responsive patients. Treating the right patient with the right biologic, and therefore biologic response prediction, has become a major point of interest in severe asthma management. A variety of response outcomes is utilized in the different clinical trials, as well as a huge range of potential predicting factors. Also, regarding the timing of the response evaluation, there are considerable differences between studies. This review summarizes the results from studies on predicting responses and responders to biological treatment in severe asthma, taking into account clinical, functional and inflammatory parameters assessed prior to the start of treatment as well as following a few months of therapy. In addition, future perspectives are discussed, highlighting the need for more research to improve patient identification and treatment responses in the field of biological treatment in severe asthma.

Purpose Peripheral neuropathy (PN) is common in patients with multiple myeloma (MM). We hypothesized that the relationship between hypovitaminosis D and PN described in diabetes mellitus patients may also be present in MM patients. Methods To study this potential association, we assessed the incidence of hypovitaminosis D (vitamin D < 75 nmol/L [= 30 ng/mL]) in smouldering and active MM patients in two Dutch hospitals. Furthermore, a validated questionnaire was used to distinguish different PN grades. Results Of the 120 patients included between January 2017 and August 2018, 84% had an inadequate vitamin D level (median vitamin D level 49.5 nmol/L [IQR 34–65 nmol/L]; mean age: 68 years [SD ± 7.7]; males: 58%). PN was reported by 69% of patients (n = 83); however, of these 83 patients, PN was not documented in the medical records of 52%. An association was found between lower vitamin D levels and higher incidence of PN in the total population (P = 0.035), and in the active MM patients (P = 0.016). Conclusion This multi-centre cohort study showed that PN and hypovitaminosis D are common in MM patients, and addressing low vitamin D levels in the treatment of MM patients might be beneficial in reducing the risk of PN. More attention for PN is warranted, as PN is underreported by clinicians. Further research is needed to fully understand the implications of vitamin D in the development of PN in patients with MM. Clinical trial registration Netherland Trial Register NL5835, date of registration July 28, 2016

IntroductionAnti-interleukin-5/5Ra therapy has shown to reduce maintenance oral corticosteroid dose in severe eosinophilic asthma. However, the effect on cumulative oral corticosteroid exposure is currently unknown. Neither is it known how prior oral corticosteroid exposure affects response to anti-interleukin-5/5Ra treatment. We aimed primarily to compare the cumulative oral corticosteroid exposure over a 2-year period before and after anti-interleukin-5/5Ra initiation, and secondarily to investigate whether duration and cumulative oral corticosteroid exposure prior to anti-interleukin-5/5Ra influence the ability to discontinue oral corticosteroids within 2 years of anti-interleukin-5/5Ra therapy.MethodsThis real-world nationwide observational registry-based study evaluated all dispensed oral corticosteroids from 389 adults with severe eosinophilic asthma included in the Dutch severe asthma registry (RAPSODI) 2 years before and 2 years after initiating anti- interleukin-5/5Ra. Wilcoxon-signed rank test and multivariable regression analyses were used.ResultsMedian (IQR) cumulative oral corticosteroid exposure in the 2 years before and after anti-interleukin-5/5Ra initiation decreased from 2.715 g (1.150–5.539) to 1.050 g (0.300–3.640), p<0.001. Fifty-two percent of patients were able to discontinue oral corticosteroids within 2 years anti-interleukin-5/5Ra therapy, which was independently predicted by lower and shorter prior oral corticosteroid exposure.ConclusionThis real-world study showed that anti-interleukin-5/5Ra therapy leads to a significant reduction in cumulative oral corticosteroid exposure over a 2-year period. Patients with lower and shorter oral corticosteroids exposure were more likely to completely eliminate oral corticosteroids. Since cumulative exposure increased progressively prior to anti-interleukin-5/5Ra initiation, our data suggest that early intervention leads to a better long-term prognosis in patients with severe eosinophilic asthma.

Real-world evidence from multinational disease registries is becoming increasingly important not only for confirming the results of randomized controlled trials, but also for identifying phenotypes, monitoring disease progression, predicting response to new drugs, and early detection of rare side effects. With new open access technologies, it has become feasible to harmonize patient data from different disease registries and use it for data analysis without compromising privacy rules. In this article, we provide a blueprint for how a clinical research collaboration can successfully use real-world data from existing disease registries to perform federated analyses. We describe how the European Severe Asthma Clinical Research Collaboration SHARP fulfilled the harmonization process from non-standardized clinical registry data to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) and built a strong network of collaborators from multiple disciplines and countries. The blueprint covers organizational, financial, conceptual, technical, analytical and research aspects and discusses both the challenges and the lessons learned. All in all, setting up a federated data network is a complex process that requires thorough preparation, but above all, it is a worthwhile investment for all clinical research collaborations, especially in view of the emerging applications of artificial intelligence and federated learning.

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