Lifetime impact of achondroplasia study in Europe (LIAISE): findings from a multinational observational study

Abstract

Background Achondroplasia, caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene, is the most common skeletal dysplasia. The Lifetime Impact of Achondroplasia Study in Europe (LIAISE; NCT03449368) aimed to quantify the burden of achondroplasia among individuals across a broad range of ages, including adults. Methods Demographic, clinical and healthcare resource use data were collected from medical records of achondroplasia patients enrolled in 13 sites across six European countries in this retrospective, observational study. Descriptive statistics or event rates per 100 person-years were calculated and compared across age groups as well as by history of limb lengthening. Patient-reported outcomes (quality of life [QoL], pain, functional independence, work productivity and activity impairments) were evaluated using questionnaires at the time of enrolment. An exploratory analysis investigated correlations between height (z-score or centimetres) and patient-reported outcomes. Results Overall, 186 study patients were included, with a mean age of 21.7 ± 17.3 years (range 5.0–84.4). At least one complication or surgery was reported for 94.6% and 72.0% of patients, respectively, at a rate of 66.6 and 21.5 events per 100 person-years. Diverse medical and surgical complications were reported for all ages in a bimodal distribution, occurring more frequently in the youngest and oldest age groups. A total of 40 patients had previously undergone limb lengthening (capped at 20% per the study protocol). The most frequent surgery types varied by age, in line with complication profiles. Healthcare resource use was high across all age groups, especially among the youngest and oldest individuals, and did not differ substantially according to history of limb lengthening. Compared to general population values, patients reported impaired QoL particularly for physical functioning domains. In addition, patients reported difficulty carrying out daily activities independently and pain starting in childhood. Patient height correlated with multiple patient-reported outcomes. Conclusions The findings of this study suggest that, across an individual’s lifetime, achondroplasia is associated with multisystem complications, reduced QoL and functionality, and increased pain. These results highlight the large amount of healthcare resources that individuals with achondroplasia require throughout their lifespans and provide novel insights into current achondroplasia management practices across Europe. Trial registration ClinicalTrials.gov, NCT03449368, Submitted 14 December 2017 – prospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT03449368

Higher rates of non-skeletal complications and greater healthcare needs in achondroplasia compared to the general UK population: a matched cohort study using the CPRD database

“…The study also highlighted that individuals with ACH more frequently experience pain, urinary incontinence, problems with the digestive system, seizures and depression/anxiety than the general UK population, require increased medication use and have an increased surgical burden across age groups. These findings support and add to the existing literature base [ 5 , 13 , 14 , 21 , 27 ], while highlighting the multi-disciplinary care needed for those with ACH [ 26 ].…”

Unveiling the Chaos in Postural Control in Adults with Achondroplasia

“…It is estimated that around 250.000 PwACH exist worldwide [ 7 ], a reduced number of people compared with more prevalent conditions. However, as knowledge expands, stability optimization through individualized strength and activity promotion will become more likely and may afford this population the equitable opportunity to fulfil societal roles and activities that enrich wellbeing.…”

“…To increase height, a surgical procedure defined by lower limb lengthening (intervention) has been an option for PwACH since the early 20th century [ 5 ]. The prevalence of limb lengthening varies from 1.2% in a study from the USA [ 6 ] to 21.5% in a study in Europe [ 7 ], with higher prevalence in Spain and Italy. The intervention functions based on external fixators and, more recently, intramedullary nails [ 8 ] to distract long bones, allowing new bone formation in between.…”

European Achondroplasia Forum Practical Considerations for Following Adults with Achondroplasia

“…Achondroplasia is a lifelong condition with associated lifelong medical complications that can have significant impact on physical functioning, daily activities, pain, and psychosocial health. Adults with achondroplasia have been found to have lower physical and psychosocial health than people without, alongside higher rates of anxiety, depression, and low self-esteem [ 5 , 12 , 54 , 55 ]. This demonstrates the need for lifelong care [ 1 , 2 ], but how that care is delivered is vital.…”