Juvenile Autoimmune Necrotizing Myopathies (MYONECPED)

Clinical, Paraclinical, Functional Characteristics and Evolution of Juvenile Autoimmune Necrotizing Myopathies in a National Retrospective Cohort

Autoimmune necrotizing myopathies (AINM) in adult patients are characterized by severity of muscle damage, presence of necrosis with little inflammation on muscle biopsy and anti-HMGCR or anti-SRP auto-antibodies. Data on AINM in children are currently lacking. The purpose of this study is to specify the characteristics at AINM diagnosis, treatments and evolution of juvenile AINM with anti-HMGCR or anti-SRP antibodies.

Study Overview

• Status: Unknown
• Conditions: Immune-Mediated Necrotizing Myopathy

• Study Type: Observational
• Enrollment (Anticipated): 10

Contacts and Locations

• Study Contact: Name: Irène LEMELLE; Phone Number: 03 83 15 45 96; Email: i.lemelle@chru-nancy.fr

Study Locations

• France
  • Vandœuvre-lès-Nancy, France, 54 500
    • Hopital d'enfants CHRU Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

AINM histologically proved (i.e. predominant muscle fibers necrosis lesions associated with minimal or absent inflammatory lesions), either anti-SRP or anti-HMGCR antibodies positivity and a disease onset before age 18

Description

Inclusion Criteria:

• AINM histologically proved by predominant muscle fibers necrosis lesions associated with minimal or absent inflammatory lesions
• Either anti-SRP or anti-HMGCR antibodies positivity
• Disease onset before age 18

Exclusion Criteria:

• Seronegative necrotizing myopathies
• Forms compatible with another type of myositis (e.g. dermatomyositis)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
autoimmune necrotizing myopathy beginning before 18

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of muscle involvment	Proximal or distal or axial muscle involvement by muscle testing	At diagnosis
Type of cutaneous involvment	Rash or Gottron lesions	At diagnosis
Other clinical manifestations	Dysphagia or dyspnea or fever or interstitial lung involvement or articular involvement or gastrointestinal involvment	At diagnosis
Blood CK level	Blood CK level	At diagnosis
Histology	Results of muscle biopsy : necrosis	At diagnosis
Histology	Results of muscle biopsy : inflammation	At diagnosis
MMT score	MMT score	At diagnosis
CMAS score	CMAS score	At diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of drugs used	Drugs ever used : name and duration	At last visit
Iatrogenic complications	Infectious complications	At last visit
Iatrogenic complications	Bone complications	At last visit
Status of the disease at last visit	Status of the disease at last visit : active or remission or death	At last visit
Number of relapses	Number of relapses	At last visit
Type of muscle involvment	Proximal or distal or axial muscle involvement by muscle testing	At last visit
Type of cutaneous involvment	Rash or Gottron lesions	At last visit
Other clinical manifestations	Dysphagia or dyspnea or fever or interstitial lung involvement or articular involvement or gastrointestinal involvment	At last visit
Blood CK level	Blood CK level	At last visit
CMAS score	CMAS score	At last visit
MMT score	MMT score	At last visit

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Publications and helpful links

General Publications

• Benveniste O, Stenzel W, Allenbach Y. Advances in serological diagnostics of inflammatory myopathies. Curr Opin Neurol. 2016 Oct;29(5):662-73. doi: 10.1097/WCO.0000000000000376.
• Mariampillai K, Granger B, Amelin D, Guiguet M, Hachulla E, Maurier F, Meyer A, Tohme A, Charuel JL, Musset L, Allenbach Y, Benveniste O. Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies. JAMA Neurol. 2018 Dec 1;75(12):1528-1537. doi: 10.1001/jamaneurol.2018.2598.
• Watanabe Y, Uruha A, Suzuki S, Nakahara J, Hamanaka K, Takayama K, Suzuki N, Nishino I. Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1038-44. doi: 10.1136/jnnp-2016-313166. Epub 2016 May 4.
• Allenbach Y, Drouot L, Rigolet A, Charuel JL, Jouen F, Romero NB, Maisonobe T, Dubourg O, Behin A, Laforet P, Stojkovic T, Eymard B, Costedoat-Chalumeau N, Campana-Salort E, Tournadre A, Musset L, Bader-Meunier B, Kone-Paut I, Sibilia J, Servais L, Fain O, Larroche C, Diot E, Terrier B, De Paz R, Dossier A, Menard D, Morati C, Roux M, Ferrer X, Martinet J, Besnard S, Bellance R, Cacoub P, Arnaud L, Grosbois B, Herson S, Boyer O, Benveniste O; French Myositis Network. Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Medicine (Baltimore). 2014 May;93(3):150-157. doi: 10.1097/MD.0000000000000028.
• Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients. J Rheumatol. 2017 Sep;44(9):1417. doi: 10.3899/jrheum.160871.C1. No abstract available.
• Liang WC, Uruha A, Suzuki S, Murakami N, Takeshita E, Chen WZ, Jong YJ, Endo Y, Komaki H, Fujii T, Kawano Y, Mori-Yoshimura M, Oya Y, Xi J, Zhu W, Zhao C, Watanabe Y, Ikemoto K, Nishikawa A, Hamanaka K, Mitsuhashi S, Suzuki N, Nishino I. Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies. Rheumatology (Oxford). 2017 Feb;56(2):287-293. doi: 10.1093/rheumatology/kew386. Epub 2016 Nov 6.
• Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, Parks CA, Casciola-Rosen L, Christopher-Stine L, Mammen AL. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017 May 1;56(5):787-794. doi: 10.1093/rheumatology/kew470.
• Binns EL, Moraitis E, Maillard S, Tansley S, McHugh N, Jacques TS, Wedderburn LR, Pilkington C, Yasin SA, Nistala K; UK Juvenile Dermatomyositis Research Group (UK and Ireland). Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature. Pediatr Rheumatol Online J. 2017 Oct 31;15(1):77. doi: 10.1186/s12969-017-0205-x.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2020
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Autoimmune necrotizing myopathy; anti-HMGCR antibodies; anti-SRP antibodies
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Muscular Diseases
• Other Study ID Numbers: 2019PI192

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No