Plexiform neurofibromas are benign tumors, but the burden they create is anything but benign: this survey links NF1 with lower quality of life for patients and measurable productivity loss for caregivers. Plexiform neurofibromas are complex, benign nerve-sheath tumours that occur in 30 to 50 percent of patients with neurofibromatosis type 1, a rare genetic disorder.

These tumours are associated with substantial, heterogeneous morbidities that impact health-related quality of life, including affecting motor function and causing pain. Because health-related quality of life and work productivity data are scarce, this UK cross-sectional study explored both outcomes in adult patients with NF1 and plexiform neurofibromas and caregivers of paediatric patients.

Neurofibromatosis type 1 is a progressive genetic disorder affecting approximately one in three thousand children and adults in European populations. A common feature, reported in 30 to 50 percent of patients, is the presence of plexiform neurofibromas.

Plexiform neurofibromas are benign but often progressive tumours arising from nerves, and they can occur anywhere on the body. Their size, location and invasiveness can cause pain, disfigurement and motor deficits, as well as potentially life-threatening complications such as airway obstruction.

Data on the impact of NF1, particularly NF1 with plexiform neurofibromas, on patients' or caregivers' health-related quality of life and work productivity, including health utilities, remain scarce. A small number of studies have suggested that patients with NF1 have poorer health-related quality of life than the general population, with emotional wellbeing, social functioning, mental health, appearance, sleep, pain and daily activities affected.

Negative emotional, social and productivity impacts have also been observed in caregivers of patients with NF1 and plexiform neurofibromas. The exploratory study quantitatively assessed the impact of NF1 with plexiform neurofibromas on health-related quality of life and caregiver work productivity, and estimated utilities for adult patients and caregivers of paediatric patients.

It also examined the relationship between patient characteristics and health-related quality of life. This exploratory, cross-sectional, non-interventional study consisted of two anonymous surveys directed at adult patients with NF1 and plexiform neurofibromas and caregivers of paediatric patients with NF1 and plexiform neurofibromas, respectively, in March to April 2021.

The study followed a pre-specified protocol including a statistical analysis plan. Ethical approval was obtained from the London – West London and Gene Therapy Advisory Committee Research Ethics Committee. The choice of patient and caregiver health-related quality of life and work productivity measures was informed by a targeted literature review of previous studies in NF1 and related conditions.

Patients completed the generic and disease-specific measures EQ-5D-5L, PROMIS Global Health and the Impact of NF1 on Quality of Life measure. Caregivers completed EQ-5D-5L, the Care-Related Quality of Life measure and the Work Productivity and Activity Impairment questionnaire as adapted for caregiving.

Fifty-one eligible adult patients started the survey, but 35 of those 51 patients provided answers to all questions relating to their clinical and demographic characteristics. The numbers of patients answering each specific question ranged from 33 to 49.

Of the 51 eligible patients who started the survey, scores came from 35 patients who completed EQ-5D and PROMIS Global Health, and from 33 patients who completed the Impact of NF1 on Quality of Life measure. The mean estimated EQ-5D utility was 0.65 among 35 patients, substantially worse than the age- and sex-matched general population estimated mean of 0.89.

Fourteen of 35 patients, or 40 percent, reported moderate to extreme pain or discomfort. Eighteen of 35 patients, or 51.4 percent, reported moderate to extreme anxiety or depression. Table 2 summarizes health-related quality of life in adults with NF1 using several measures.

The estimated EQ-5D utility score had a mean of zero point six five, with values from zero point four two to zero point eight four; overall health was most often rated as good, at sixteen participants, or forty-five point seven percent. For INF1-QOL, thirty-three scores were estimable, with a mean total score of eleven point zero three and a range from one to twenty-six.

The mean caregiver EQ-5D utility was 0.72, substantially worse than the age- and sex-matched general population estimated mean of 0.88. Moderate pain or discomfort was reported by 4 of 8 caregivers, or 50 percent, and slight to severe problems with anxiety or depression were also reported by 4 of 8 caregivers.

The CarerQol overall utility score was 69.3, with a standard deviation of 13.9. Table three summarizes health-related quality of life and caregiver well-being for eight survey respondents. The EQ-5D-5L domains include mobility, self-care, usual activities, pain or discomfort, and anxiety or depression; the mean utility score was zero point seven two, with a range from zero point three one to one point zero zero.

CarerQol reported a mean utility score of sixty-nine point three and a mean happiness score of five point six three, while work-productivity questions were applicable according to employment status. In the caregiver Work Productivity and Activity Impairment questionnaire, almost a quarter of worktime was missed due to caregiving: mean absenteeism was 24.5 percent.

Productivity while at work was impaired by 40.0 percent, and the resulting mean productivity loss was 42.9 percent. Mean regular activity productivity loss, meaning the extent to which caregiving impaired productivity during daily activities, was 36.3 percent.

The study's limitations include low participant numbers, especially in the caregiver survey, possibly leading to uncertainty and lack of powering, as evidenced by the wide confidence intervals. Qualitative interviews or mixed methods may improve results obtained in the future.

The online survey approach may have resulted in voluntary response bias and sampling bias, while electronic-only advertising likely prevented a minority of people from participating. Because the study was cross-sectional and exploratory, it was not possible to infer causal relationships, and significance testing and comparisons with existing literature must be interpreted with care.

In this exploratory UK survey, adults with NF1 and plexiform neurofibromas reported substantially poorer health-related quality of life, while caregivers also reported impaired wellbeing and productivity. The findings show why the wider burden of NF1 PN matters.