Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without ...corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide FENO, blood eosinophils, and serum periostin) with a standardised symptom–risk-based algorithm (control).
We did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at 12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed.
Patients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n=240) or to the control group (n=61). 28·4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18·5% of patients in the control group (adjusted odds ratio aOR 1·71 95% CI 0·80–3·63; p=0·17). In the per-protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30·7% of patients) compared with the control group (5·0% of patients; aOR 11·48 95% CI 1·35–97·83; p=0·026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose.
Biomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low.
This study was funded, in part, by the Medical Research Council UK.
Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom ...(UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.
26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected
electronic survey.
24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD.
We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.
Oral mucositis (OM) is an adverse effect of myeloablative regimens which seriously affects patient well-being and may increase risk of systemic infection and delay recovery. Trial-based reports of OM ...occurrence vary widely, with evidence of underreporting, and data on the incidence and impact of OM in routine practice are limited. Initiated by the European Group for Blood and Marrow Transplantation, this study observed pts. with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL) from 25 transplant centres across 13 European countries, receiving high dose melphalan or BEAM followed by autologous stem-cell transplant. Aims were to assess duration and incidence of severe (WHO oral toxicity scale Grade III–IV) OM and ulcerative (Grade II–IV) OM, medical resource use for OM prevention and treatment, and associations with infection and duration of hospitalisation. Prospective OM assessments were conducted daily from the start of conditioning until 30 days post transplant or hospital discharge. To achieve high and consistent quality of OM assessment, nurse assessors underwent a multimedia-assisted face-to-face training before study initiation. Of 197 evaluable pts., 110 (56%) had MM and 87 (44%) had NHL. Mean age at enrolment ± SD was 57 ± 8 years for MM and 50 ± 13 years for NHL. Women accounted for 36% of the MM sample and 51% of the NHL sample. In both sub-samples, 94% of pts. had ECOG status ≤ 1. The incidence of severe OM was 46% (95% CI 37–56%) for MM and 41% (95% CI 31–52%) for NHL. Severe OM episodes had a mean duration of 5.4 ± 3.3 days (95% CI 4.6–6.3 days) in MM and 5.3 ± 3.2 days (95% CI 4.3–6.4 days) in NHL. Ulcerative OM occurred in 67% (95% CI 58–76%) of MM pts. and 60% (95% CI 49–70%) of NHL pts., with a mean duration of 6.6 ± 4.4 days (95% CI 5.6–7.6 days) and 6.5 ± 3.8 days (95% CI 5.6–7.7 days), respectively. WHO scale results and indicators of specific OM symptoms showed very similar temporal patterns, reaching their maximum around day 12 after the start of conditioning in both groups. Clinically relevant associations with type of disease/conditioning or gender were not detected. A non-statistically significant trend hinted at an association of OM duration with age. The incidence of fever ≥ 38° C was 68% in pts. with severe OM vs. 47% in pts. without (univariate p = 0.004; odds ratio 2.4, 95% CI 1.3–4.4). Mean length of stay ± SD (truncated at 30 days post transplant) was 21.1 ± 4.0 days in pts. with severe OM vs. 19.9 ± 4.8 days in pts. without (univariate p = 0.023). Preliminary multivariate analysis adjusting for other potential predictors confirmed these effects. Based on a close collaboration of nurses and physicians, this study showed severe OM to be a substantial clinical problem in pts. receiving high dose melphalan or BEAM conditioning chemotherapy. Associations with fever occurrence and length of stay indicate potentially harmful clinical sequelae and relevant economic consequences. Associations with confirmed infection, and resource use for OM management, remain to be assessed.
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