South–West of England’s Experience of the Safety and Tolerability Pirfenidone and Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

Purpose: Pirfenidone and nintedanib are two novel antifibrotic agents licensed for the treatment IPF. Prior to being approved for use in England for patients with FVC >50% and <80%, these were made available for all IPF patients under the Mild Patient Program (MPP) and Patient In Need Scheme (PIN). Prescribing of these medications is restricted to specialist centers. We sought to characterize the population of patients prescribed antifibrotics and determine the drug tolerability of these medications in the Northern hub of the Southwest of England regional ILD network.Methods: A retrospective analysis of all patients treated with antifibrotics between August 2012 and July 2017 was undertaken. Baseline characteristics including patient demographics and pulmonary physiology, in addition to drug tolerability and reasons for treatment cessation were collated. Data were compared using unpaired student’s t-test, Chi-squared, Mann–Whitney rank sum or ANOVA as appropriate. Logistic regression analysis evaluated clinical characteristics associated with discontinuation of pirfenidone therapy. P < 0.05 was considered statistically significant.Findings: A total of 164 patients, all with consensus diagnoses of IPF, were identified. Of these, 70.1% (115/164) received pirfenidone as their initial therapy. Baseline age, gender and pulmonary physiology did not differ significantly between groups. Drug discontinuation occurred most commonly due to adverse drug reactions events (ADRs) for both pirfenidone [40.0% (46/115)] and nintedanib [16.3% (8/49)]. Anorexia, rash and gastrointestinal disturbance were reported most commonly as the reason for cessation of pirfenidone; anorexia, nausea and weight loss for nintedanib. Duration of therapy prior to discontinuation because of ADRs did not differ significantly between medication groups but patients with a baseline FVC < 65% predicted, had a significantly shorter duration of pirfenidone prior to discontinuation due to ADRs, compared to those with a FVC 65–80% predicted. Multivariate logistic regression did not identify any independent baseline characteristics that predicted discontinuation of pirfenidone therapy prior to 52 weeks.Implications: Idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib had comparable treatment emergent adverse event (TEAE) profiles in clinical practice to those reported in clinical trials. The TEAE profile of pirfenidone was higher than clinical trial data would suggest, although comparable to real-world datasets. Further work is required to explore the possible reasons underpinning this finding, including whether this is related to population co-morbidities or center threshold. No new safety concerns were identified

Long-term nitrofurantoin:an analysis of complication awareness, monitoring, and pulmonary injury cases

BACKGROUND: Long-term nitrofurantoin (NF) treatment can result in pulmonary and hepatic injury. Current guidelines do not outline the type or frequency of monitoring required for detection of these injuries. AIM: To assess 1) awareness of NF complications among prescribers; 2) monitoring practice; and 3) to describe the pulmonary sequelae of NF-related complications. DESIGN & SETTING: Evaluation of prescribing habits by questionnaires and review of GP databases, and case-note review in secondary care. METHOD: The following study procedures were undertaken: 1) an electronic questionnaire was distributed to prescribers, interrogating prescribing and monitoring practices, and awareness of complications; 2) an analysis was undertaken (June–July 2020) of NF monitoring among GPs in the local clinical commissioning group (CCG); and 3) a case review was carried out of patients diagnosed with NF-induced interstitial lung disease (NFILD) at the interstitial lung disease (ILD) centre (2014–2020). RESULTS: A total of 125 prescribers of long-term NF responded to the questionnaire (82.4% GPs; 12.0% urologists). Many were unaware of the potential for liver (42.4%) and lung (28.0%) complications; 40.8% and 52.8% never monitored for these, respectively. Only 53.3% of urologists believed themselves responsible for arranging monitoring, while nearly all GPs believed this to be the prescriber’s responsibility (94.2%). One-third of all responders considered current British National Formulary (BNF) guidelines 'not at all sufficient/clear', with mean clarity scoring of 2.2/5. Among patients with NFILD (n = 46), NF had been prescribed most often (69.6%) for treatment of recurrent UTI and 58.6% (n = 27) were prescribed for >6 months. On withdrawal of the medication 61.4% displayed resolution (completely or minimal fibrosis), while 15.9% of patients had progressive lung fibrosis. CONCLUSION: NF can cause marked or irreversible lung complications and there is currently a shortfall in awareness and monitoring. Existing monitoring guidelines should be augmented

Patient outcomes after hospitalisation with COVID-19 and implications for follow-up:results from a prospective UK cohort

The longer-term consequences of SARS-CoV-2 infection are uncertain. Consecutive patients hospitalised with COVID-19 were prospectively recruited to this observational study (n=163). At 8–12 weeks postadmission, survivors were invited to a systematic clinical follow-up. Of 131 participants, 110 attended the follow-up clinic. Most (74%) had persistent symptoms (notably breathlessness and excessive fatigue) and limitations in reported physical ability. However, clinically significant abnormalities in chest radiograph, exercise tests, blood tests and spirometry were less frequent (35%), especially in patients not requiring supplementary oxygen during their acute infection (7%). Results suggest that a holistic approach focusing on rehabilitation and general well-being is paramount

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK

Background 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.Methods 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 via electronic survey.Results 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.Conclusion 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

Clinicoserological features of antisynthetase syndrome (ASyS)-associated interstitial lung disease presenting to respiratory services:comparison with idiopathic pulmonary fibrosis and ASyS diagnosed in rheumatology services

INTRODUCTION: Antisynthetase syndrome (ASyS) is a rare autoimmune connective tissue disease (CTD), associated with autoantibodies targeting tRNA synthetase enzymes, that can present to respiratory (interstitial lung disease (ILD)) or rheumatology (myositis, inflammatory arthritis and systemic features) services. The therapeutic management of CTD-associated ILD and idiopathic pulmonary fibrosis (IPF) differs widely, thus accurate diagnosis is essential.METHODS: We undertook a retrospective, multicentre observational cohort study designed to (1) evaluate differences between ASyS-associated ILD with IPF, (2) phenotypic differences in patients with ASyS-ILD presenting to respiratory versus rheumatology services, (3) differences in outcomes between ASySassociated with Jo-1 versus non-Jo-1 autoantibodies and (4) compare long-term outcomes between these groups.RESULTS: We identified 76 patients with ASyS-ILD and 78 with IPF. Patients with ASyS were younger at presentation (57 vs 77 years, p&lt;0.001) with a female predominance (57% vs 33%, p=0.006) compared with IPF. Cytoplasmic staining on indirect immunofluorescence was a differentiating factor between ASyS and IPF (71% vs 0%, p&lt;0.0001). Patients with ASyS presenting initially to respiratory services (n=52) had a higher prevalence of ASyS non-Jo-1 antibodies and significantly fewer musculoskeletal symptoms/biochemical evidence of myositis, compared with those presenting to rheumatology services (p&lt;0.05), although lung physiology was similar in both groups. There were no differences in high-resolution CT appearances or outcomes in those with Jo-1 versus non-Jo-1 ASyS-ILD.CONCLUSIONS: Extended autoimmune serology is needed to evaluate for ASyS autoantibodies in patients presenting with ILD, particularly in younger female patients. Musculoskeletal involvement is common in ASyS (typically Jo-1 autoantibodies) presenting to rheumatology but the burden of ILD is similar to those presenting to respiratory medicine.</p

A multidisciplinary approach to the diagnosis of antisynthetase syndrome

Antisynthetase syndrome is a subtype of idiopathic inflammatory myopathy, strongly associated with the presence of interstitial lung disease. Diagnosis is made by identifying myositis-specific antibodies directed against aminoacyl tRNA synthetase, and relevant clinical and radiologic features. Given the multisystem nature of the disease, diagnosis requires the careful synthesis of subtle clinical and radiological features with the interpretation of specialized autoimmune serological testing. This is provided in a multidisciplinary environment with input from rheumatologists, respiratory physicians, and radiologists. Differentiation from other idiopathic interstitial lung diseases is key; treatment and prognosis differ between patients with antisynthetase syndrome and idiopathic interstitial lung disease. In this review article, we look at the role of the multidisciplinary team and its individual members in the initial diagnosis of the antisynthetase syndrome, including the role of physicians, radiologists, and the wider team