Patient-reported symptom severity of Charcot-Marie-Tooth disease type 1A: findings from a digital real-world study

Thomas FP¹, Attarian S², Sevilla T³, Genovese F⁴, Gray AJ⁵, Bull S⁶, Tanesse D⁷, Moore A⁸, Hollett C⁸, Paoli

Day L¹⁰, Kudlac A¹⁰, Lau JKL¹⁰, Llewellyn S¹⁰, Larkin M¹⁰, Boutalbi Y⁹

¹Department of Neurology, Hackensack Meridian School of Medicine, Hackensack University Medical Center, Hackensack, NJ, USA ²Hospital University la Timone, Filnemus ERN-NMD, Marseille, France

³Hospital Universitari I Politècnic La Fe, Universitate de Valencia, CIBERER, Valencia, Spain⁴ACMT-Rete per la malattia di Charcot-Marie-Tooth OdV, Bologna, Italy⁵Charcot-Marie-Tooth Association, Glenolden, PA, USA

⁶Charcot-Marie-Tooth UK, Christchurch, UK⁷CMT France, Saint-Alban, France⁸Hereditary Neuropathy Foundation, NewYork, NY, USA⁹Pharnext, Paris, France¹⁰Vitaccess, Oxford, UK

Corresponding author: Youcef Boutalbi, yboutalbi@pharnext.com

Background &Objectives

Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited rare peripheral nerve disease leading to progressive, predominantly distal muscle weakness, atrophy, sensory loss, and limb deformities1,2

This analysis explores the relationship between disease severity in CMT1A and a range of clinical variables.

Symptom severity

Results for the symptom severity linear regression model are shown in Fig. 2. There were 530 responses to the survey (over multiple timepoints), and a range of explanatory variables had an effect on symptom severity in the model. The regression model was statistically significant overall (Adj. R2 = 0.264, F = 4.714), indicating a good fit of the model to the data.

Beta represents the coefficient in the model, showing the direction and magnitude of the effect on the PRO outcome variable.

Adults with CMT1A in France, Germany, Italy, Spain, the UK, or the USA were recruited to an ongoing, international, digital study exploring the real-world impact of CMT. Data on symptom severity were collected via a bespoke single-question patient-reported outcome (PRO) instrument, administered on the study app, CMT&Me. Participants evaluated the current severity of their symptoms using four response options: none, mild, moderate, and severe.

Linear regression was used to evaluate relationships between the PRO responses and a series of explanatory clinical variables; these variables include demographics, symptoms, medical history, and treatment history. Explanatory variables in the model comprise data collected at registration, while the PRO outcome variable in the model comprise data collected at the most recent timepoint of completion.

The symptom severity linear regression model is shown in Fig. 1.

The “Severe” classification (1)comprises “severe” response choice only, and the “Non-severe” classification (0) comprises the remaining response options, “none” to “moderate”.

Methods Results

Country of residence

The country of residence (reported at registration) of the 1,030 respondents in the analysis population is presented in Table 1.

Residency in France (ß=0.2, p=0.003), Germany (ß=0.428, p<0.001), Italy (ß=0.209, p=0.012), Spain (ß=0.246, p=0.001), and the UK (ß=0.131, p=0.019) was associated with greater severity of symptoms when compared with residency in the USA (reference category).

Diagnosis age of 0 to 10 years (ß=0.166, p=0.005) or diagnosis age of 11 to 20 years (ß=0.132, pp=0.016) was associated with greater severity of symptoms when compared with diagnosis age of 31 to 40 years (reference category).

Reporting of a greater time in years from symptom onset to diagnosis (ß=0.004, p=0.006), weakness in the arms (ß=0.168, p<0.001), hearing loss (ß=0.116, p=0.013), difficulty breathing (ß=0.15, p=0.005), burning (ß=0.165, p=0.001), and severe fatigue (ß=0.202, p<0.001) was associated with greater severity of symptoms.

Reported use of CBD oil (ß=0.132, p=0.036) or codeine (ß=0.162, p=0.017) was associated with greater severity of symptoms.

Discussion &Conclusions

This study evidences a range of clinical variables predicting the impact on symptom severity in CMT1A, including an association between an earlier age of disease onset and greater time from symptom onset to diagnosis with greater symptom severity. Further exploration of such interactions could increase understanding of disease burden and improve CMT1A disease management.

Figure 1: Symptom severity linear regression model

Figure 2: Symptom severity linear regression model results (n=530 responses; p<0.05)

Table 1: Country of residence (n=1,030)

Sereda M, Nave KA. Animal Models of Charcot-Marie-Tooth Disease Type 1A. NeuroMolecular Medicine. 2006;8:205-16. 2 Attarian S, Young P, Brannagan TH, Adams D, Van Damme P, Thomas FP, et al. A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A. Orphanet Journal of Rare Diseases. 2021;16(1):1-12.

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