Efficacy and safety of treatment with biologicals (benralizumab,dupilumab, mepolizumab,omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV₁, without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV₁. More data on long-term safety are needed together with more efficacy data in the paediatric population.     

CCNU (lomustine), idarubicin and dexamethasone (CIDEX): an effective oral regimen for the treatment of refractory or relapsed myeloma

We report the results of a non-randomized pilot study of an oral regimen comprising CCNU (lomustine; 25 or 50 mg/m2 on day 1), idarubicin (4-demethoxydaunorubicin) (10 mg/m2 on days 1-3) and dexamethasone (10 mg b.d. on days 1-4) in patients with relapsed or refractory myeloma. Treatment was given every 28 d for a maximum of six courses. Sixty patients were entered of whom 57 were evaluable. Overall response rate (partial or minor response) was 49% with 30% of patients achieving a partial response (50% tumour reduction). Response rates were higher in patients with untested relapse than in those with refractory disease (overall response rates 56% vs. 31%). The major toxicity was neutropenia and the regimen was otherwise well tolerated. The median survival from entry of all patients was 15 months, with 30% of patients alive at 2 years. This regimen represents a useful addition to available treatment options.     

Intracranial aneurysmal bone cyst manifesting as a cerebellar mass

A 17-year-old boy presented with symptoms of raised intracranial pressure for a month. Investigations revealed a large extra-cerebellar mass. The lesion was radically resected. It arose from the petrous bone. Histology revealed that the lesion was an aneurysmal bone cyst [ABC].     

Involvement of a humoral factor in regulation of body weight in parabiotic rats.

Excessive food intake and obesity was induced in one member of parabiotic pairs by electrical stimulation (three 30-min sessions/day for 2 wk) of the lateral hypothalamus (LH). The nonstimulated partners reduced spontaneous food intake the fatter the stimulated animals became. This reduced food intake resulted in a decreased body weight, fat content, and fat-free solid body mass. The decrease of food intake was not due to changed social behavior of the obese partner. It must be attributed to transmission of a humoral satiety factor. The very first stimulation of the LH in the stimulated partners resulted in a large increase in blood glucose and glucagon level without much change in the insulin level. These changes in blood parameters were probably due to strong sympathetic arousal. In the nonstimulated animals there were practically no changes in these parameters. One week of fattening resulted in increased basal glucose and insulin levels in the stimulated animals and decreased glucose levels in the nonstimulated partners, in which the basal insulin levels remained nearly normal. Basal glucagon levels were the same in both partners and did not differ from the prefattening situation. At that time during stimulation the obese animals showed a large increase in glucose and glucagon levels and a decrease in insulin level. On the other hand the nonstimulated animals showed a slow gradual increase in glucose and insulin level due to transmission from their fat partners because of the large gradient in these substances between the animals. These phenomena were still more pronounced after 2 wk of fattening. It is tentatively concluded that the humoral satiety factor is neither circulating insulin nor glucagon nor one of the major circulating nutrients.