BioDrugs

Asthma management guidelines emphasise the importance of treatment of the underlying airways inflammation. Inhaled corticosteroids play a central role in this and have an impressive record of efficacy and safety. Detailed assessments, however, reveal that not all patients respond equally well to these drugs. Residual symptoms are usually treated with short-acting β-agonists. Some studies have suggested that short-acting β-agonists, while effective relievers of symptoms, might have adverse effects on the underlying control of the asthma. The newer long-acting β-agonists have been viewed with some suspicion in light of this. Critical examination of the data suggests that, although the short-acting β-agonists may have some potentially adverse effects, these are unlikely to have a significant clinical manifestation unless the drugs are used in excess; the long-acting β-agonists appear to have a very good safety record. Thus, in patients who remain symptomatic despite taking moderate dosages of inhaled corticosteroids, the question arises as to whether they are always better treated by increasing the dosage of the inhaled corticosteroid or whether the addition of a long-acting β-agonist to the existing dosage of inhaled corticosteroid would be more satisfactory. Two recent large multicentre studies indicate that the latter option may be more effective. Nevertheless, analyses of group data often conceal the variability between individual responses, and arguments can be made that patients who have relatively stable disease but with regular symptoms may be better served by adding a long-acting β-agonist to the existing dosage of inhaled corticosteroid, whereas patients with symptoms and a record of exacerbations of asthma may be better served by increasing the dosage of inhaled corticosteroid.

This study aimed to analyse the clinical features and outcomes of and reasons for discontinuing tumour necrosis factor (TNF) inhibitor therapy in older patients with ankylosing spondylitis (AS). Data were extracted from the nationwide Korean College of Rheumatology Biologics registry. Clinical variables and outcomes were compared, and drug retention rate was evaluated. Among 1524 patients with AS treated with TNF inhibitors, 306 were aged ≥ 50 years (‘older patients’). Fewer patients were male, the incidence of hypertension and diabetes was higher (all p < 0.001), and the proportion of peripheral arthritis (35.6 vs. 27.1%), Ankylosing Spondylitis Disease Activity Score‒erythrocyte sedimentation rate (4.0 ± 1.1 vs. 3.6 ± 1.0), and Bath Ankylosing Spondylitis Functional Index (4.2 ± 2.6 vs. 3.3 ± 2.5) were all higher in older patients. Although the drug retention rate was lower (log-rank p = 0.018) and lack of efficacy and adverse events were more frequent in older patients (both p < 0.001), drug retention rates were not different after propensity score matching (log-rank p = 0.23). Improvements in disease activity and manifestations were comparable between groups, except for the incidence of peripheral arthritis, which decreased significantly less in older patients over 3 and 5 years. Improvements in disease-related clinical factors and drug retention rates were not different between older and younger patients with AS receiving TNF inhibitors. However, the incidence of adverse events was higher in older patients.

Calcitonin gene-related peptide (CGRP), a neuropeptide abundant in the trigeminal system and widely expressed in both the peripheral and central nervous systems, has recently emerged as a promising target for migraine management. While known as a potent arterial vasodilator, the role of CGRP in migraine is likely mediated by modulating nociception and sustaining neurogenic inflammation that leads to further peripheral and central pain sensitization. Functional blockade of CGRP, which involves either CGRP receptor antagonists or monoclonal antibodies (mAbs) to CGRP or its receptor, has recently shown clinical efficacy in migraine management. The site of action, although still being studied, is likely in nervous system structures outside the blood–brain barrier. To date, four CGRP function-blocking mAbs (three target CGRP and one targets the CGRP receptor) are under clinical investigation for migraine prophylaxis. Phase II and III studies were promising with favorable safety profiles. CGRP function-blocking mAbs may potentially revolutionize the management of migraine. This review discusses in depth the fundamental role of CGRP in migraine pathogenesis as well as the clinical efficacy of CGRP function-blocking mAbs.

The current problems with increasing bacterial resistance to antibacterial therapies, resulting in a growing frequency of incurable bacterial infections, necessitates the acceleration of studies on antibacterials of a new generation that could offer an alternative to antibiotics or support their action. Bacteriophages (phages) can kill antibiotic-sensitive as well as antibiotic-resistant bacteria, and thus are a major subject of such studies. Their efficacy in curing bacterial infections has been demonstrated in in vivo experiments and in the clinic. Unlike antibiotics, phages have a narrow range of specificity, which makes them safe for commensal microbiota. However, targeting even only the most clinically relevant strains of pathogenic bacteria requires large collections of well characterized phages, whose specificity would cover all such strains. The environment is a rich source of diverse phages, but due to their complex relationships with bacteria and safety concerns, only some naturally occurring phages can be considered for therapeutic applications. Still, their number and diversity make a detailed characterization of all potentially promising phages virtually impossible. Moreover, no single phage combines all the features required of an ideal therapeutic agent. Additionally, the rapid acquisition of phage resistance by bacteria may make phages already approved for therapy ineffective and turn the search for environmental phages of better efficacy and new specificity into an endless race. An alternative strategy for acquiring phages with desired properties in a short time with minimal cost regarding their acquisition, characterization, and approval for therapy could be based on targeted genome modifications of phage isolates with known properties. The first example demonstrating the potential of this strategy in curing bacterial diseases resistant to traditional therapy is the recent successful treatment of a progressing disseminated Mycobacterium abscessus infection in a teenage patient with the use of an engineered phage. In this review, we briefly present current methods of phage genetic engineering, highlighting their advantages and disadvantages, and provide examples of genetically engineered phages with a modified host range, improved safety or antibacterial activity, and proven therapeutic efficacy. We also summarize novel uses of engineered phages not only for killing pathogenic bacteria, but also for in situ modification of human microbiota to attenuate symptoms of certain bacterial diseases and metabolic, immune, or mental disorders.

Rhesus (Rh) isoimmunisation is the most common form of severe haemolytic disease of the newborn (HDN). The introduction of prophylaxis with anti-D Rh0 immunoglobulin (anti-D) has resulted in a marked reduction in the sensitisation of Rh-negative women and deaths attributable to Rh HDN. The sensitisation rate could be further decreased if there was strict adherence to the guidelines for administration of anti-D prophylaxis. Whether additional prophylaxis at 28 and 34 weeks of gestation would be cost effective is controversial. Intrauterine transfusions to treat fetal anaemia, postnatal exchange transfusions and phototherapy are all part of the standard management of affected individuals. Intravenous immunoglobulin given to pregnant women can reduce fetal haemolysis, and when administered to neonates with Rh isoimmunisation has been associated with a reduction in the requirement for exchange transfusion. There are, however, potential risks of immunoglobulin administration, including haemolysis due to the presence of anti-A or anti-B antibodies, allergy and the transmission of disease.