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Lung transplant recipients (LTRs) respond poorly to vaccination. SARS-CoV-2 pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab (TIX/CIL) reduces the incidence of infection and the evolution to severe COVID-19. In vitro data show decreased activity against Omicron variants. We evaluated the clinical efficacy and safety of TIX/CIL in LTRs during the Omicron wave. A prospective observational cohort study was conducted at ISMETT in Palermo (Italy). In June 2022, SARS-CoV-2 PrEP with TIX/CIL 150/150 mg was offered to LTRs. LTRs who received TIX/CIL were compared to LTRs who did not. Logistic regression analysis (adjusted for prior COVID-19, SARS-CoV-2 vaccination, age, years from transplant, and rejection) was performed. The objective of this study was to compare the following among the two populations: prevalence of SARS-CoV-2, length of SARS-CoV-2 positivity, and COVID-19 disease severity. Among 110 eligible LTRs, 79 (72%) received TIX/CIL and 31 (28%) did not. SARS-CoV-2 infections occurred in 6% (n = 5) of patients who received TIX/CIL and 29% (n = 9) of patients who did not (p < 0.001). In both groups, infections were mild/asymptomatic, and no one was hospitalized or died. At multivariate analysis, TIX/CIL was associated with a lower risk of infection (aOR 0.22; 95%CI 0.06-0.78; p = 0.02). TIX/CIL was safe and effective in reducing the risk of SARS-CoV-2 in LTRs during the Omicron wave.
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BACKGROUND: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools. METHODS: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score. RESULTS: These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6-2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18-0.47, p < 0.001). CONCLUSIONS: Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.
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Pulmonary arterial hypertension is characterized by elevated blood pressure and pathological changes in the pulmonary arterioles, leading to the development of right-heart failure and potentially fatal outcomes if left untreated. This review aims to provide an overview of novel drugs or formulations and new drug indications for pulmonary arterial hypertension that are currently in phases II-III of randomized controlled trials, and describe the rationale for the use of these targeted therapies, as well as their efficacy, safety profile, and impact on quality of life and survival. The literature research was conducted using data from ClinicalTrials.gov for the period between 1 January 2016 up to 31 December 2022. The population of interest includes individuals aged ≥ 18 years who have been diagnosed with pulmonary arterial hypertension. The review selection criteria included trials with recruiting, enrolling by invitation, active, terminated or completed status in 2022 and 2023. A total of 24 studies were selected for evaluation based on the inclusion and exclusion criteria. This review summarizes the updated information from randomized clinical trials involving novel therapies for pulmonary arterial hypertension. However, larger clinical trials are required to validate their clinical safety and effects. In the future, clinicians should choose therapies based on the patient's individual situation and requirements when developing treatment strategies.
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Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Antihipertensivos/uso terapéutico , Antihipertensivos/farmacología , Antihipertensivos/efectos adversos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Calidad de VidaRESUMEN
Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.
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Cardiología , Sistema Cardiovascular , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Disfunción Ventricular Derecha , Humanos , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/tratamiento farmacológicoRESUMEN
Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes.
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Pulmonary hypertension (PH) associated with interstitial lung disease (ILD) is an attractive target for clinical trials of PH medications. There are many factors that need to be considered to prime such studies for success. The patient phenotype most likely to respond to the intervention requires weighing the extent of the parenchymal lung disease against the severity of the hemodynamic impairment. The inclusion criteria should not be too restrictive, thus enabling recruitment. The trial should be of sufficient duration to meet the chosen endpoint which should reflect how the patient feels, functions, or survives. This paper summarizes prior studies in PH-ILD and provides a framework of the type of studies to be considered. Inclusion criteria, clinical trial endpoints, and pharmacovigilance in the context of PH-ILD trials are also addressed. Through lessons learnt from prior studies, suggestions and guidance for future clinical trials in PH-ILD are also provided.
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Rationale: Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods: The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Results: Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion: Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.
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Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2.
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Vacunas contra la COVID-19 , COVID-19 , Receptores de Trasplantes , Humanos , Anticuerpos Antivirales , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Inmunidad , Inmunoglobulina A , Inmunoglobulina G , Trasplante de Órganos/efectos adversos , SARS-CoV-2 , Vacunas de ARNmRESUMEN
Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in-depth papers on specific topics pertaining to PH-ILD.
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Background: Several studies have indicated that anti-SARS-CoV-2 mRNA vaccinations are less effective in inducing robust immune responses among solid organ transplant recipients (SOTRs) compared with the immunocompetent. The third dose of vaccine in SOTRs showed promising results of immunogenicity, even though clinical studies have suggested that immunocompromised subjects are less likely to build a protective immune response against SARS-CoV-2 resulting in lower vaccine efficacy for the prevention of severe COVID-19. Methods: Serological IgG and IgA were analyzed through CLIA or ELISA, respectively, while Spike-specific T cells were detected by ELISpot assay after the second and third dose of vaccine in 43 SOTRs. Results: The third dose induced an improvement in antibody response against SARS-CoV-2. We also reported a strong correlation between specific humoral and cellular responses after the third dose, even though we did not see significant changes in the magnitude of the SARS-CoV-2-specific T cell response. SOTRs who contracted the SARS-CoV-2 infection after the third dose, despite eliciting a positive IgG response, failed to mount an anti-Spike-S1 IgA response, both after the third dose and after SARS-CoV-2 infection. Conclusions: We can conclude that serum IgA detection can be helpful, along with IgG detection, for the evaluation of vaccine efficacy, principally in fragile subjects at high risk of infection.
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BACKGROUND: The impact of the new "borderline" hemodynamic class for pulmonary hypertension (PH) (mean pulmonary artery pressure [mPAP], 21-24 mm Hg and pulmonary vascular resistance, [PVR], ≥3 wood units, [WU]) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is unclear. OBJECTIVES: The aim of this study was to assess the effect of borderline PH (BLPH) on survival in COPD and ILD patients. METHOD: Survival was analyzed from retrospective data from 317 patients in 12 centers (Italy, Spain, UK) comparing four hemodynamic groups: the absence of PH (NoPH; mPAP <21 mm Hg or 21-24 mm Hg and PVR <3 WU), BLPH (mPAP 21-24 mm Hg and PVR ≥3 WU), mild-moderate PH (MPH; mPAP 25-35 mm Hg and cardiac index [CI] ≥2 L/min/m2), and severe PH (SPH; mPAP ≥35 mm Hg or mPAP ≥25 mm Hg and CI <2 L/min/m2). RESULTS: BLPH affected 14% of patients; hemodynamic severity did not predict survival when COPD and ILD patients were analyzed together. However, survival in the ILD cohort for any PH level was worse than in NoPH (3-year survival: NoPH 58%, BLPH 32%, MPH 28%, SPH 33%, p = 0.002). In the COPD cohort, only SPH had reduced survival compared to the other groups (3-year survival: NoPH 82%, BLPH 86%, MPH 87%, SPH 57%, p = 0.005). The mortality risk correlated significantly with mPAP in ILD (hazard ratio [HR]: 2.776, 95% CI: 2.057-3.748, p < 0.001) and notably less in COPD patients (HR: 1.015, 95% CI: 1.003-1.027, p = 0.0146). CONCLUSIONS: In ILD, any level of PH portends worse survival, while in COPD, only SPH presents a worse outcome.
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Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Pulmón , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Estudios RetrospectivosRESUMEN
OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.
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COVID-19 , Hipertensión Arterial Pulmonar , Progresión de la Enfermedad , Hipertensión Pulmonar Primaria Familiar , Humanos , Péptido Natriurético Encefálico , Hipertensión Arterial Pulmonar/epidemiología , SARS-CoV-2RESUMEN
Notch-1 pathway plays an important role in lung carcinoma, stem cell regulation, cellular communication, growth and differentiation. Cigarette smoke is involved in the regulation of Notch signaling. However, current data regarding the impact of cigarette smoke on the Notch pathway in lung cancer progression are limited. The present study aimed to explore whether cigarette smoke exposure altered Notch-1 pathway in ex-vivo (surgical samples of lung parenchyma from non-smoker and smoker patients with lung adenocarcinoma) and in vitro (adenocarcinoma A549 cell line) approaches. The expression of Notch-1, Jagged-1 and CD133 in surgical samples was evaluated by immunohistochemistry. A549 were exposed to cigarette smoke extracts (2.5 % and 5 % CSE for 6, 24 and 48 h) and the expression of Notch-1, Jagged-1 and Hes-1 was evaluated by Real-Time PCR and Western Blot (nuclear fractions). Expression and localization of Notch-1, Hes-1, CD133 and ABCG2 were assessed by immunofluorescence. The expression of survivin and Ki-67 was assessed by flow cytometry following CSE exposure and inhibition of Notch-1 signaling. Smokers lung parenchyma exhibited higher expression of Notch-1. CSE exposure increased Notch-1 and Hes-1 gene and nuclear protein expression in A549. Immunofluorescence confirmed higher expression of nuclear Hes-1 in CSE-stimulated A549 cells. CSE increased both survivin and Ki-67 expression and this effect was reverted by inhibition of the Notch-1 pathway. In conclusion, these data show that cigarette smoke may promote adenocarcinoma progression by activating the Notch-1 pathway thus supporting its role as hallmark of lung cancer progression and as a new target for lung cancer treatment.
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Adenocarcinoma del Pulmón/metabolismo , Fumar Cigarrillos , Pulmón/metabolismo , Receptor Notch1/metabolismo , Células A549 , Antígeno AC133/genética , Antígeno AC133/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Western Blotting , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Pulmón/efectos de los fármacos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Notch1/genética , Transducción de Señal , Fumadores , Survivin/genética , Survivin/metabolismo , Factor de Transcripción HES-1/genética , Factor de Transcripción HES-1/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most serious long-term complication of acute pulmonary embolism (PE) though it is the only potentially reversible form of pulmonary hypertension (PH). Its incidence is mainly limited to the first 2 years following the embolic event, however it is often underdiagnosed or misdiagnosed. METHODS: This is a multicenter observational cross-sectional and prospective study. Patients with a prior diagnosis of PE will be enrolled and undergo baseline evaluation for prevalent PH detection through a clinical examination and an echocardiogram as first screening exam. All cases of intermediate-high echocardiographic probability of PH will be confirmed by right heart catheterization and then identified as CTEPH through appropriate imaging and functional examinations in order to exclude other causes of PH. A CTEPH Risk Score will be created using retrospective data from this prevalent cohort of patients and will be then validated on an incident cohort of patients with acute PE. RESULTS: One thousand retrospective and 218 prospective patients are expected to be enrolled and the study is expected to be completed by the end of 2021. Up to now 841 patients (620 retrospective and 221 prospective) have been enrolled. CONCLUSIONS: This study is the first large prospective study for the prediction of CTEPH development in patients with PE. It aims to create a comprehensive scoring tool that includes echocardiographic data which may allow early detection of CTEPH and the application of targeted follow-up screening programs in patients with PE.
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Hipertensión Pulmonar , Embolia Pulmonar , Enfermedad Aguda , Estudios Transversales , Diagnóstico Precoz , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Estudios Prospectivos , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The role of PAR-1 expression and activation was described in epithelial cells from the central and distal airways of COPD patients using an ex vivo/in vitro model. PAR-1 immunoreactivity was studied in epithelial cells from surgical specimens of the central and distal airways of COPD patients and healthy control (HC). Furthermore, PAR-1 expression and activation were measured in both the human bronchial epithelial cell line (16HBE) and normal human bronchial epithelial cells (NHBEs) exposed to cigarette smoke extract (CSE) (10%) or thrombin. Finally, cell proliferation, apoptosis, and IL-8 release were detected in stimulated NHBEs. We identified higher levels of PAR-1 expression/activation in epithelial cells from the central airways of COPD patients than in HC. Active PAR-1 increased in epithelial cells from central and distal airways of COPD, with higher levels in COPD smokers (correlated with pack-years) than in COPD ex-smokers. 16HBE and NHBEs exposed to CSE or thrombin showed increased levels of active PAR-1 (localized in the cytoplasm) than baseline conditions, while NHBEs treated with thrombin or CSE showed increased levels of IL-8 proteins, with an additional effect when used in combination. Smoking habits generate the upregulation of PAR-1 expression/activation in airway epithelial cells, and promoting IL-8 release might affect the recruitment of infiltrating cells in the airways of COPD patients.
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Expresión Génica , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Receptor PAR-1/genética , Receptor PAR-1/metabolismo , Mucosa Respiratoria/metabolismo , Apoptosis/genética , Biomarcadores , Estudios de Casos y Controles , Línea Celular , Proliferación Celular , Susceptibilidad a Enfermedades , Células Epiteliales/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Interleucina-8/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Mucosa Respiratoria/patología , Fumar/efectos adversosAsunto(s)
SARS-CoV-2 , Vacunas , Vacuna BNT162 , Vacunas contra la COVID-19 , Humanos , Inmunidad Celular , ARN MensajeroRESUMEN
BACKGROUND: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. OBJECTIVE: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. METHODS: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization's registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen's d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). RESULTS: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). CONCLUSION AND RELEVANCE: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.