Tamera J. Corte

American journal of respiratory and critical care medicine • January 02, 2025

Kerri Johannson, Ayodeji Adegunsoye, Jürgen Behr, Vincent Cottin, Allan Glanville, Marilyn Glassberg, Gillian Goobie, R Jenkins, John Kim, Cathryn Lee, Carrie Redlich, Luca Richeldi, Margaret Salisbury, Terry Tetley, Tamera Corte

Many fibrotic interstitial lung diseases (fILDs) are associated, either causally or indirectly, with inhaled environmental exposures. Robust epidemiologic evidence implicates multiple exposures involved in diverse ILD clinical subtypes. A growing body of translational and mechanistic data describes how inhalational damage induces and promotes profibrotic pathways, building on epidemiologic data and characterizing the pathobiology of fiLD. Although most individuals are exposed to potential inhalational toxins, only a minority develop fILD. The current fiILD paradigm suggests that an interplay of genetic-environmental interactions, timing, duration, and intensity of exposure, as well as other internal susceptibilities, mediate disease risk in the context of exposure. Characterization of this complex dynamic will inform why some individuals develop fILD, support risk management and prevention, and potentially help identify novel therapeutic exposure-mediated targets. This pulmonary perspective synthesizes current knowledge on epidemiologic and mechanistic relationships between inhaled exposures and fiLD, highlighting the importance of environmental determinants of disease and disease progression; addresses clinical implications; and advocates for prevention measures.

Therapeutic Advances In Respiratory Disease • May 03, 2025

Megan Harrison, Chloe Lawler, Fiona Lake, Vidya Navaratnam, Caitlin Fermoyle, Yuben Moodley, Tamera Corte

The interstitial lung diseases (ILDs) are a heterogeneous and complex group of diseases. The treatable trait (TT) model represents a shift in ILD management, away from traditional diagnostic labels towards a more individualised, trait-focused approach. This review explores the application of the TT paradigm to ILD, identifying key traits across the aetiological, pulmonary, extrapulmonary and behavioural domains. By addressing these traits, the TT model offers a framework to improve outcomes in ILD through multidisciplinary management with a precision medicine focus. Further research is necessary to evaluate the overall impact of this TT model on ILD care.

BMJ Open Respiratory Research • November 20, 2024

Toby Maher, Jin Song, Mordechai Kramer, Lisa Lancaster, Tamera Corte, Jeong Yun, Kyungjin Kim, Jimin Cho, Luisa Sather, Peter George, Anand Devaraj, Jin Jung, Sujin Jung

Background: Proof-of-concept (POC) studies are vital in determining the feasibility of further drug development, primarily by assessing preliminary efficacy signals with credible endpoints. However, traditional POC studies in idiopathic pulmonary fibrosis (IPF) can suffer from low credibility due to small sample sizes and short durations, leading to non-replicable results in larger phase III trials. To address this, we are conducting a 24-week POC study with 120 patients with IPF, using a statistically supported sample size and incorporating exploratory CT-based imaging biomarkers, to support decision-making in the case of non-significant primary endpoint results. This approach aims to provide data to enable a robust decision-making process for advancing clinical development of BBT-877. Methods: In this phase II, double-blind, placebo-controlled study, approximately 120 patients with IPF will be randomised in a 1:1 ratio to receive placebo or 200 mg of BBT-877 two times per day over 24 weeks, with stratification according to background use of an antifibrotic treatment (pirfenidone background therapy, nintedanib background therapy or no background therapy). The primary endpoint is absolute change in forced vital capacity (FVC) (mL) from baseline to week 24. Key secondary endpoints include change from baseline to week 24 in %-predicted FVC, diffusing capacity of the lung for carbon monoxide, 6 min walk test, patient-reported outcomes, pharmacokinetics and safety, and tolerability. Key exploratory endpoints include eLung-based CT evaluation and biomarker-based assessment of pharmacodynamics. Background: This study is being conducted following the Declaration of Helsinki principles, Good Clinical Practice guidance, applicable local regulations and local ethics committees. An independent data monitoring committee unblinded to individual subject treatment allocation will evaluate safety and efficacy data on a regular basis throughout the study. The results of this study will be presented at scientific conferences and peer-review publications. Background: NCT05483907.

Annals Of The Rheumatic Diseases • October 26, 2024

Giovanni Zanframundo, Eduardo Dourado, Iazsmin Bauer Ventura, Sara Faghihi Kashani, Akira Yoshida, Aravinthan Loganathan, Daphne Rivero Gallegos, Darosa Lim, Francisca Bozán, Gianluca Sambataro, Sangmee Bae, Yasuhiko Yamano, Francesco Bonella, Tamera Corte, Tracy Doyle, David Fiorentino, Miguel Gonzalez Gay, Marie Hudson, Masataka Kuwana, Ingrid Lundberg, Andrew Mammen, Neil Mchugh, Frederick Miller, Carlomaurizio Montecucco, Chester Oddis, Jorge Rojas Serrano, Jens Schmidt, Albert Selva O'callaghan, Victoria Werth, Paul Hansen, Davide Rozza, Carlo Scirè, Garifallia Sakellariou, Yuko Kaneko, Konstantinos Triantafyllias, Santos Castañeda, Maria Alberti, Martín Gerardo Merino, Christopher Fiehn, Yair Molad, Marcello Govoni, Ran Nakashima, Erkan Alpsoy, Margherita Giannini, Hector Chinoy, Laure Gallay, Esther Ebstein, Julien Campagne, André Saraiva, Edoardo Conticini, Gian Sebastiani, Laura Nuño, Salvatore Scarpato, Elena Schiopu, Matthew Parker, Massimiliano Limonta, Rohit Aggarwal

Objective: To develop and evaluate the performance of multicriteria decision analysis (MCDA)-driven candidate classification criteria for antisynthetase syndrome (ASSD). Methods: A list of variables associated with ASSD was developed using a systematic literature review and then refined into an ASSD key domains and variables list by myositis and interstitial lung disease (ILD) experts. This list was used to create preferences surveys in which experts were presented with pairwise comparisons of clinical vignettes and asked to select the case that was more likely to represent ASSD. Experts' answers were analysed using the Potentially All Pairwise RanKings of all possible Alternatives method to determine the weights of the key variables to formulate the MCDA-based classification criteria. Clinical vignettes scored by the experts as consensus cases or controls and real-world data collected in participating centres were used to test the performance of candidate classification criteria using receiver operating characteristic curves and diagnostic accuracy metrics. Results: Positivity for antisynthetase antibodies had the highest weight for ASSD classification. The highest-ranked clinical manifestation was ILD, followed by myositis, mechanic's hands, joint involvement, inflammatory rashes, Raynaud phenomenon, fever, and pulmonary hypertension. The candidate classification criteria achieved high areas under the curve when applied to the consensus cases and controls and real-world patient data. Sensitivities, specificities, and positive and negative predictive values were >80%. Conclusions: The MCDA-driven candidate classification criteria were consistent with published ASSD literature and yielded high accuracy and validity.

American Journal Of Respiratory And Critical Care Medicine • October 11, 2024

Tamera Corte, Juergen Behr, Vincent Cottin, Marilyn Glassberg, Michael Kreuter, Fernando Martinez, Takashi Ogura, Takafumi Suda, Marlies Wijsenbeek, Elchonon Berkowitz, Brandon Elpers, Sinae Kim, Hideaki Watanabe, Aryeh Fischer, Toby Maher

Rationale: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. Objectives: Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF. Methods: This phase 2, randomized, double-blind, placebo-controlled trial included parallel cohorts of patients with IPF (n = 278 randomized, n = 276 treated) or PPF (n = 125 randomized, n = 123 treated) who received 30 mg of admilparant, 60 mg of admilparant, or placebo (1:1:1) twice daily for 26 weeks. Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted. Measurements and Main Results: Rates of change in percentage of predicted FVC over 26 weeks for IPF were -2.7% (placebo), -2.8% (30 mg), and -1.2% (60 mg) and for PPF were -4.3% (placebo), -2.9% (30 mg), and -1.1% (60 mg). Treatment differences between 60-mg admilparant and placebo were 1.4% (95% confidence interval, -0.1 to 3.0) for IPF and 3.2% (95% confidence interval, 0.7 to 5.7) for PPF. Treatment effect was observed with or without background antifibrotics in both cohorts. Diarrhea occurred at similar frequencies in admilparant arms versus placebo. Transient Day 1 postdose blood pressure reductions were observed in all arms in both cohorts but were greater with admilparant. Treatment discontinuations because of adverse events were similar across IPF arms and lower with admilparant (2.5% [30 mg]; 0% [60 mg]) versus placebo (17.1%) for PPF. Conclusions: In this first phase 2 study to evaluate antifibrotic treatment in parallel IPF and PPF cohorts, 60-mg admilparant slowed lung function decline and was safe and well tolerated, supporting further evaluation in phase 3 trials. Clinical trial registered with clinicaltrials.gov identifier (NCT04308681).