Background/Aims The IMPACT survey explored self-reported experiences of the clinical, humanistic, and economic impact of osteogenesis imperfecta (OI), a rare hereditary connective tissue disorder associated with low bone mass, bone fragility and variable secondary features. Here we present findings on OI-related signs, symptoms and events and their impact on adults with OI both globally and in the United Kingdom (UK). Methods Together with the Osteogenesis Imperfecta Federation Europe and the Osteogenesis Imperfecta Foundation (USA) we developed an international survey in eight languages (fielded online July-September 2021). The survey was open to adults (aged >= 18 years) or adolescents (aged >= 12-17 years) with OI, caregivers (with or without OI) of individuals with OI and other close relatives; overall 2,278 individuals participated. Survey domains included demographics, socioeconomic factors, clinical characteristics, treatment patterns, quality of life (QoL) and health economics. Non-English language responses were translated into English. Data were cleaned, coded, and analysed using Microsoft Excel. Results 1,440 adult respondents (70.0% females, mean age 43 years) described their OI as mild (35.2%), moderate (46.6%) and severe (14.2%). Additionally, type 1 (37.7%), 3 (15.6%) and 4 (11.0%) OI were most frequently reported. Over a 12-month period, the most frequently reported clinical signs, symptoms and events were pain (81.8%), ranked as moderately or severely impactful by 68.0% of individuals who had experienced it, fatigue (66.9%), which moderately-severely impacted 69.1% and soft tissue problems or injuries (including muscle, tendon, ligament; 54.8%), which moderately-severely impacted 71.2%. While nearly one-third (27.4%) of adults experienced fractures, almost two-thirds (64.7%) of them ranked the symptom as moderately or severely impactful. In comparison, in the UK (n=144 adults; 73.6% women, mean age 47 years), over a third (36.8%) of adults reported experiencing a fracture, with nearly three-quarters (73.6%) ranking it as moderately or severely impactful. Leg fractures were more commonly reported (mean 0.3 fractures, standard deviation [SD] 2.2) among adults in the overall survey population compared with rib (mean 0.3, SD 1.1), vertebral (mean 0.2, SD 0.9) or arm (mean 0.1, SD 1.0) fractures. In contrast, the most prevalent fracture type among the UK cohort were rib fractures (mean 0.4, SD 1.1). Across all QoL domains, the impact of OI was greater among individuals who had experienced fractures, compared with those who had not. Additionally, demographic and clinical factors such as sex, OI severity, OI type and the experience of fractures were identified as drivers of QoL impact. Conclusion Adults with OI experience a wide range of OI-related clinical signs, symptoms and events. Irrespective of an individual's characteristics, fractures are associated with worsened QoL. Further analysis will elucidate the impact of this complex condition and provide insights into areas of improvement of treatment, care and policy making. Disclosure O. Semler: Other; O.S. has participated in a national advisory board for Mereo BioPharma Group London, United Kingdom. L.L. Wekre: None. I. Westerheim: Other; I.W holds leadership positions in the Osteogenesis Imperfecta Federation Europe, which has received grants from Mereo BioPharma Group, London, United Kingdom (unrestricted), Ultragenyx Pharmaceuticals Inc, Novato, USA (restricted grant for a conference), Quince Therapeutics Inc, San Francisco, CA, USA (donation for a conference), UCB (restricted grant to conference), Angitia Biopharmaceuticals Inc., Woodland Hills, CA, USA (donation to conference), Azafaros BV, Naarden, the Netherlands (donation to conference), Alexion Inc. Boston, MA, USA, (sponsorship of conference); Pega Medical Inc, Laval, Quebec, Canada (donation), Sanofi S.A. Paris, France (payment to IW for engagement in steering committee; donated to OIFE), I.W. has also received payment as a panellist from Takeda, Tokyo, Japan. T.V. Welzenis: None. C. Raggio: Grants/research support; C.R. has received an institutional grant from and has been a speaker for BioMarin Pharmaceuticals Inc, Novato, California, C.R has received an institutional grant from and is a consultant for Nextcure, Beltville, MD, USA. Other; C.R. has participated in advisory boards for Ultragenyx Pharmaceuticals Inc, Novato, USA, CR sits on the board of directors of the Osteogenesis Imperfecta Foundation and on the medical board of the Osteogenesis Imperfecta Federation Europe, CR has also participated in an advisory board for Mereo BioPharma Group, London, United Kingdom. T. Hart: Grants/research support; TH has received unrestricted educational grants from Mereo BioPharma Group London, United Kingdom and Ultragenyx Pharmaceuticals Inc, Novato, USA. Other; T.H. serves as the Chief Executive Officer of the Osteogenesis Imperfecta Foundation. R. Dadzie: Other; R.D. is an employee of Wickenstones Ltd. L. Dewavrin: Other; L.D. is an employee of Wickenstones Ltd. S. Prince: Other; S.P. is an employee of Wickenstones Ltd. F. Rauch: Other; F.R. has received study contracts for experimental preclinical studies with Precithera Inc, Quebec, Canada, Mesentech Inc, Vancouver, Canada and Catabasis Pharmaceuticals Inc, Cambridge, USA, F.R. has participated in advisory boards for Ultragenyx Pharmaceuticals Inc, Novato, USA, Sanofi S.A. Paris, France, Novartis International AG, Basel, Switzerland and Mereo BioPharma Group, London, United Kingdom, F.R. has received a speaker fee from Ultragenyx Pharmaceuticals Inc, Novato, USA for a lecture and received a donation of experimental drugs for a preclinical study from Acceleron Pharma Inc, Cambridge, USA.
