{
  "abstract": "Introduction TRAJECTORY is an ongoing, observational, medical record (MR) abstraction study in the United Kingdom, Canada, Germany, Italy, Portugal and Spain among people with CF (PwCF) who initiated elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) August 2019 – June 2023. We assessed long-term effects of ELX/TEZ/IVA on clinical outcomes and quality of life (QoL) in PwCF aged ≥12 years with a minimum of 12 months and up to 36 months of ELX/TEZ/IVA treatment.Methods MR data from 42 sites were collected for 12 months before ELX/TEZ/IVA initiation (baseline) and up to 5 years after (follow-up). Outcomes included body mass index (BMI), percent predicted forced expiratory volume in one second (ppFEV 1), annualized event rates of PEx and hospitalizations, and QoL (self-report using the Cystic Fibrosis Questionnaire-Revised [CFQ-R; Child 12–13, Teen-Adult 14+]). Descriptive analyses were stratified by prior CF transmembrane conductance regulator modulator (CFTRm) use and baseline ppFEV1. Outcomes were evaluated at 12 months, 24 months, and 36 months post-ELX/TEZ/IVA initiation.Results Of 508 PwCF aged ≥12 years with ≥12 months of follow-up, ~50.0% were female (49.6%, 252/508), homozygous for F508del-CFTR (50.0%, 254/508), and had prior CFTRm use (48.4%, 246/508). At ELX/TEZ/IVA initiation, mean (SD) age, ppFEV1, and BMI were 30.4 (12.8) years, 63.2 (24.0) and 21.5 (3.6) kg/m2. At initiation, 58.5% had ppFEV1 between 40 and 90 (ppFEV1 ≥40 to <70: 36.8%, 187/508; ppFEV1 ≥70 to ≤90: 21.7%, 110/508). After 36 months, ELX/TEZ/IVA treatment led to mean (SD) increases in BMI (+1.9 kg/m2 [2.2]) and ppFEV1 (+9.3 percentage points [10.1]), and decreases in annualized event rates of PEx (0.4 to 0.3) and hospitalizations (1.0 to 0.5).Regardless of prior CFTRm use, all CFQ-R domain mean scores showed improvement at 12 months, 24 months, and 36 months. The largest domain increases in mean (SD) absolute change from baseline at 36 months were Respiratory Symptoms (26.3 [19.3]), Health Perceptions (15.3 [18.3]), Physical Functioning (12.2 [19.6]), School Functioning (+12.0 [16.2]), Vitality (9.7 [17.6]) and Treatment Burden (9.1 [14.4]) (table 1).Abstract S68 Table 1Summary of Mean CFQ-R Domains at Baseline and Change from Baseline CFQ-R Domain1 Patients Aged ≥ 12 with at least 12 months post-ELX/TEZ/IVA initiation (N = 508) Patients Aged ≥ 12 with at least 24 months post-ELX/TEZ/IVA initiation (N = 403) Patients Aged ≥ 12 with at least 36 months post-ELX/TEZ/IVA initiation (N = 189) n Baseline 2 Mean (SD) n Average absolute change 3 from baseline to 0- 12 months Mean (SD) n Baseline 2 Mean (SD) n Average absolute change 3 from baseline through 24 months Mean (SD) n Baseline 3 Mean (SD) n Average absolute change 3 from baseline through 36 months Mean (SD) Respiratory Symptoms 290 63.0 (21.7) 258 +23.4 (20.1) 210 61.9 (21.7) 202 +23.5 (19.2) 74 58.4 (22.7) 71 +26.3 (19.3) Body Image 290 70.0 (24.9) 260 +7.9 (17.1) 210 70.7 (24.8) 204 +8.3 (18.4) 74 69.1 (24.8) 71 +8.5 (21.2) Digestive Symptoms 290 77.8 (19.9) 257 +4.4 (17.2) 210 77.9 (19.8) 203 +3.7 (16.1) 74 76.7 (21.3) 71 +4.1 (17.3) Eating Problems 290 86.7 (20.2) 260 +5.6 (16.9) 210 88.6 (19.5) 204 +4.3 (17.6) 74 87.7 (20.9) 71 +5.1 (20.6) Emotional Functioning 290 73.6 (20.5) 260 +6.6 (15.7) 210 73.9 (20.4) 204 +5.8 (16.3) 74 71.3 (19.8) 71 +7.7 (15.5) Health Perceptions 267 57.4 (24.6) 244 +15.4 (20.3) 200 56.1 (24.7) 195 +16.2 (19.5) 73 50.4 (24.9) 70 +15.3 (18.3) Physical Functioning 289 68.9 (25.7) 259 +13.8 (20.8) 210 67.6 (25.9) 204 +13.7 (19.1) 74 64.3 (24.3) 71 +12.2 (19.6) School Functioning 265 77.9 (20.8) 240 +8.3 (15.8) 198 77.1 (20.6) 192 +8.0 (15.4) 71 73.0 (20.9) 69 +8.2 (16.5) Social Functioning 290 64.3 (19.8) 260 +8.9 (15.7) 210 63.1 (19.2) 204 +10.4 (15.6) 74 58.2 (16.9) 71 +12.0 (16.2) Treatment Burden 289 59.6 (22.5) 259 +8.3 (16.1) 210 59.8 (22.8) 204 +8.4 (17.6) 74 59.6 (22.1) 71 +9.1 (14.4) Vitality 266 57.7 (21.9) 243 +11.5 (19.6) 200 56.9 (22.7) 195 +9.8 (18.6) 73 53.3 (22.0) 70 +9.7 (17.6) Weight 266 70.9 (36.0) 241 +11.7 (30.5) 200 72.0 (35.9) 193 +9.7 (32.3) 73 79.9 (29.8) 70 +6.5 (29.3) CFQ-R: Cystic Fibrosis Questionnaire – Revised; ELX/TEZ/IVA: elexacaftor/tezacaftor/ivacaftor; SD, standard deviation. Please note that this is a medical chart abstraction study where CFQ-R is collected as part of standard of care. Not all sites collected the CFQ-R as part of the standard of care. The counts vary by domain and study duration. Each domain yields a standardized score ranging from 0–100, with higher scores indicating better health-related quality of life. 1For the analyses of CFQ-R domains Respiratory Symptoms, Body, Digestion, Eating Problems, Emotional Functioning, Physical Functioning, Social Functioning and Treatment Burden, CFQ-R data from patients aged 12 – 13 and data from patients aged ≥ 14 were pooled. 2For the analyses of CFQ-R domains Respiratory Symptoms, Body, Digestion, Eating Problems, Emotional Functioning, Physical Functioning, Social Functioning and Treatment Burden, CFQ-R data from patients aged 12 – 13 and data from patients aged ≥ 14 was pooled. 2Start of ELX/TEZ/IVA therapy is defined as the study baseline. 3Average absolute change through the post-baseline is calculated as the average of all measurements during the post-baseline period minus baseline. Measurements within four weeks following ELX/TEZ/IVA initiation are excluded.Conclusions ELX/TEZ/IVA treatment showed substantial benefits in clinical outcomes and QoL in the real-world setting with sustained improvement up to at least 36 months for PwCF aged ≥12 years.",
  "authors": [
    {
      "affiliations": [
        "University of Toronto, Hospital for Sick Children, Toronto, Canada"
      ],
      "name": "F Ratjen"
    },
    {
      "affiliations": [
        "HMU University Potsdam, Potsdam, Germany"
      ],
      "name": "C Schwarz"
    },
    {
      "affiliations": [
        "Ospedale Maggiore Policlinico, Fondazione IRCCS Ca, Milano, Italy"
      ],
      "name": "V Daccò"
    },
    {
      "affiliations": [
        "University Hospital Llandough, Penarth, UK"
      ],
      "name": "J Duckers"
    },
    {
      "affiliations": [
        "Hospital Universitario Y Politécnico La Fe, University of Valencia, Valencia, Spain"
      ],
      "name": "A Solé"
    },
    {
      "affiliations": [
        "H. Santa Maria. Centro Hospitalar Lisboa Norte, Lisboa, Portugal"
      ],
      "name": "P Azevedo"
    },
    {
      "affiliations": [
        "University Hospitals of Leicester, Leicestershire, UK"
      ],
      "name": "MI Ahmed"
    },
    {
      "affiliations": [
        "Hospitais da Universidade de Coimbra, ULS Coimbra, Coimbra, Portugal"
      ],
      "name": "F Gamboa"
    },
    {
      "affiliations": [
        "Borgo Trento, Ospedale Civile Maggiore, AOU Integrata Verona, Verona, Italy"
      ],
      "name": "M Cipolli"
    },
    {
      "affiliations": [
        "St. Paul’s Hospital, Vancouver, Canada"
      ],
      "name": "BS Quon"
    },
    {
      "affiliations": [
        "Vertex Pharmaceuticals, Incorporated, Boston, USA"
      ],
      "name": "QN Do"
    },
    {
      "affiliations": [
        "Vertex Pharmaceuticals, Incorporated, Boston, USA"
      ],
      "name": "E Muller"
    },
    {
      "affiliations": [
        "Vertex Pharmaceuticals, Incorporated, Boston, USA"
      ],
      "name": "M Jennings"
    },
    {
      "affiliations": [
        "Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Essen, Germany"
      ],
      "name": "S Sutharsan"
    },
    {
      "affiliations": [
        "UK"
      ],
      "name": "TNS the TRAJECTORY Study Team"
    }
  ],
  "title": "S68 Long-term effects of elexacaftor/tezacaftor/ivacaftor on clinical outcomes and quality of life among adolescents and adults aged 12+ with cystic fibrosis: Interim results from the TRAJECTORY Study",
  "uid": "06f1c9a4-ab22-5d3b-a19f-2ef851e3d76a"
}