Patient-reported severity of pain interference in 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 X⁹, 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, Spain ⁴ACMT-Rete per la malattia di Charcot-Marie-Tooth OdV, Bologna, Italy ⁵Charcot-Marie-Tooth Association, Glenolden, PA, USA ⁶Charcot-Marie-Tooth UK, Christchurch, United Kingdom ⁷CMT France, Saint-Alban, France ⁸Hereditary Neuropathy Foundation, New York, NY, USA ⁹Pharnext, Paris, France 10Vitaccess, Oxford, United Kingdom Corresponding author: Youcef Boutalbi, yboutalbi@pharnext.com
Background & Objectives
Results
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 1,2 deformities .
Country of residence
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The country of residence (reported at registration) of the 1,030 respondents in the analysis population is presented in Table 1. Table 1: Country of residence (n=1,030) Country of residence
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. Patient-reported outcome (PRO) ® data on pain interference were collected via the PROMIS Pain Interference Short Form 6a, administered on the study app, CMT&Me. Linear regression was used to evaluate relationships between PRO responses and a series of explanatory clinical variables. The PROMIS Pain Interference linear regression model is shown in Fig. 1. The total raw score was translated into a T-score for each participant, in accordance with the official PROMIS scoring guidelines.
T-score
Worse health Severity classification
Severe (1) Non-severe (0) (LEFS <=20) (T score <70)
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Figure 1: PROMIS Pain Interference linear regression model
314 (31%)
UK (recruitment began November 2018)
255 (25%)
Italy (recruitment began January 2019)
138 (13%)
Severe (1) (T score >=70)
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Significance Non−significant Significant at p<0.05
0.0
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France (recruitment began July 2019)
133 (13%)
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Germany (recruitment began January 2019)
107 (10%)
Spain (recruitment began April 2019)
83 (8%)
Linear regression models Residency in Germany (ß=0.078, p<0.001) or the UK (ß=0.059, p=0.003) were associated with greater severity of pain interference vs the USA (reference). Beta represents the coefficient in the model, showing the direction and magnitude of the effect on the PRO outcome variable.
70 Better health
USA (recruitment began October 2018)
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Diagnosis age of 0-10 years (ß=-0.041, p=0.049) was associated with lesser severity of pain interference vs diagnosis age of 31-40 (reference). Reporting of weakness in the feet (ß=0.081, p<0.001), balance problems (ß=0.068, p=0.003), hearing loss (ß=0.076, p<0.001), hammer toes (ß=0.03, p=0.037), aching (ß=0.035, p=0.035), burning (ß=0.042, p=0.01), severe fatigue (ß=0.208, p<0.001), use of analgesics (ß=0.031, p=0.028), opioids (ß=0.094, p<0.001), CBD oil (ß=0.088, p<0.001), or neuroleptics (ß=0.067, p=0.002) were associated with greater severity of pain interference. Reporting of numbness (ß=-0.059, p=0.001), high arches (ß=-0.074, p<0.001), flat arches (ß=0.088, p<0.001), and use of antidepressants (ß=-0.051, p=0.004) or walking aids (ß=-0.027, p=0.037) were associated with lesser severity of pain interference.
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Methods
Value (n, %)
coefficients/ marginal effects
This analysis explores the relationship between pain interference in Charcot-Marie-Tooth Disease 1A (CMT1A), and multiple clinical variables.
Coefficients of Linear (Probability) Model Outcome: Pain Interference Type
Figure 2: PROMIS Pain Interference linear regression model results (n=1,573 responses from 660 responding participants; p<0.05).
Discussion & Conclusions This study evidences a range of clinical variables predicting the impact on severity of pain interference of CMT1A, including an association between use of analgesics, opioids, and CBD oil with greater pain interference. Further exploration of such interactions could increase understanding of disease burden and improve CMT1A disease management.
References 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. 1.