Drug induced interstitial lung disease: a systematic review

Skeoch, Sarah; Weatherley, Nicholas D; Swift, Andrew J.; Oldroyd, Alexander; Johns, Chris; Hayton, Conal; Giollo, A.; Wild, JM; Waterton, John C.; Buch, Maya H; Linton, Kim; Bruce, Ian N; Leonard, C.T.; Stephen, Bianchi; Chaudhuri, Nazia

doi:10.1183/13993003.congress-2018.pa2244

Cited by 60 publications

(141 citation statements)

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“…Our experience of pulmonary toxicity draws parallels with many EGFRtargeting agents, which have also been associated with an increased risk of drug-induced ILD, yet the specific mechanism remains unknown. Preclinical research directed by the TRISTAN consortium is under way to determine a general mechanism by which drug-induced ILD occurs (53). On the basis of a pooled analysis of ILD across multiple studies (multiple tumor types) of T-DXd, Japanese ethnicity and higher dose were associated with a higher risk factors for developing ILD (54).…”

Section: Discussionmentioning

confidence: 99%

Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors

et al. 2020

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HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8-11.1] months. In HER2-mutant non-small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1-14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and HER2-mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors. SIGNIFICANCE: T-DXd demonstrated promising activity in a heterogeneous patient population with heavily pretreated HER2-expressing or HER2-mutant solid tumors, especially HER2-mutant NSCLC. The safety profile was generally acceptable. Interstitial lung disease can be severe and requires prompt monitoring and intervention.

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Section: Discussionmentioning

confidence: 99%

Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors

et al. 2020

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“…[67] DiILD has overlapping chest CT findings with LD in sJIA. [68] No pathologic findings are pathognomonic of DiILD, [68,69] but PAP has been described. [24] Infection may exacerbate LD and may trigger its detection.…”

Section: Discussionmentioning

confidence: 99%

An emergent, high-fatality lung disease in systemic juvenile arthritis

Saper

Chen

Deutsch

et al. 2019

Preprint

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Objective To investigate characteristics and risk factors of a novel parenchymal lung disease, increasingly detected in systemic juvenile idiopathic arthritis (sJIA). Methods In a multi-center retrospective study, 61 cases were investigated, using physician-reported clinical information and centralized analyses of radiologic, pathologic and genetic data. Results Lung disease (LD) was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the IL-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes +/- ground glass opacities. Predominant pathology (23/36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features, including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. 5-year survival was 42%. Whole-exome sequencing (20/61) did not identify a novel monogenic defect PAP-related or macrophage activation syndrome (MAS)-related mutations as likely primary cause. Trisomy 21 (T21) increased LD risk, as did young sJIA onset. Refractory sJIA was not required for LD development. Exposure to interleukin (IL)-1 and IL-6 inhibitors (46/61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but it was not associated with LD features. Conclusions A rare, life-threatening LD in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

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“…The prescribing information from the US Food and Drug Administration (FDA) for 28 licenced drugs previously identified as being associated with a significant risk of DI-ILD in a systematic review [2] were reviewed. The FDA is a long-established regulatory agency and publishes approved prescribing information in consistent formats, whereas prescribing information in European jurisdictions is more difficult to review, particularly for older drugs that predate the establishment of the European Medicines Agency (EMA).…”

Section: Methodsmentioning

confidence: 99%

“…The three remaining manufacturers did not comment on a specific dose of corticosteroid. The ability to determine the role of corticosteroids in the treatment of DI-ILD in a recent systematic review was felt to be limited by a lack of randomised studies, as well as the problem of incomplete data regarding the dose and duration of treatment and variation in both the eligibility criteria for patient selection and corticosteroid dose [2]. The authors in this systematic review concluded that there is currently insufficient evidence on which to base recommendations for the use of corticosteroids in DI-ILD and that when corticosteroids are used, the dosing regimens used should be at the discretion of the physician treating the patient.…”

Section: Yes Nomentioning

confidence: 99%

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How consistently do physicians diagnose and manage drug-induced interstitial lung disease? Two surveys of European ILD specialist physicians

et al. 2020

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IntroductionCurrently there are no general guidelines for diagnosis or management of suspected drug-induced (DI) interstitial lung disease (ILD). The objective was to survey a sample of current European practice in the diagnosis and management of DI-ILD, in the context of the prescribing information approved by regulatory authorities for 28 licenced drugs with a recognised risk of DI-ILD.MethodsConsultant physicians working in specialist ILD centres across Europe were emailed two surveys via a website link. Initially, opinion was sought regarding various diagnostic and management options based on seven clinical ILD case vignettes and five general questions regarding DI-ILD. The second survey involved 29 statements regarding the diagnosis and management of DI-ILD, derived from the results of the first survey. Consensus agreement was defined as 75% or greater.ResultsWhen making a diagnosis of DI-ILD, the favoured investigations used (other than computed tomography) included pulmonary function tests, bronchoscopy and blood tests. The preferred method used to decide when to stop treatment was a pulmonary function test. In the second survey, the majority of the statements were accepted by the 33 respondents, with only four of 29 statements not achieving consensus when the responses “agree” and “strongly agree” were combined as one answer.ConclusionThe two surveys provide guidance for clinicians regarding an approach to the diagnosis and management of DI-ILD in which the current evidence base is severely lacking, as demonstrated by the limited information provided by the manufacturers of the drugs associated with a high risk of DI-ILD that we reviewed.

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Drug induced interstitial lung disease: a systematic review

Cited by 60 publications

References 13 publications

Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors

Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors

An emergent, high-fatality lung disease in systemic juvenile arthritis

How consistently do physicians diagnose and manage drug-induced interstitial lung disease? Two surveys of European ILD specialist physicians

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