Burden of Idiopathic Multicentric Castleman Disease (iMCD) in the US: A Population-Level Real World Analysis Using a Health-Claims Dataset
Authors: Noy Ariela , Ohgami Robert , Munshi Nikhil C. , Siddiqi Imran , Dacus Kelley C. , Watson Saltis Alicia , Shupo Francis , Princic Nicole , Evans Kristin , Mukherjee Sudipto 
Published: December 2024

Introduction: Idiopathic MCD (iMCD) is a rare non-neoplastic cytokine-driven disorder characterized by lymph node enlargement at multiple regions in the body. The epidemiology of iMCD remains poorly understood due to the rarity of the condition, diagnostic complexities and lack of population level registries in the US. An earlier analysis in 20211 used a health claims-based algorithm that included both the ICD-9-CM code for lymph node enlargement or the recently introduced CD-specific ICD-10-CM code and an adaptation of international diagnostic criteria2 to identify iMCD patients. The objectives of this current analysis were 1) to refine the administrative-claims diagnostic algorithm building on prior work from the 2021 analysis1 using only the CD-specific ICD-10-CM code and 2) to analyze the use of siltuximab, the sole treatment approved by the Food and Drug Administration (FDA) for iMCD in the US.
Methods: We used the MarketScan® by MerativeTM Commercial and Medicare administrative claims database to select patients with a diagnosis of CD (ICD-10-CM: D47Z2) from October 1 2016 - July 31 2023 (initial CD diagnosis = index). Patients with evidence of herpesvirus-8 (HHV-8) or human immunodeficiency virus (HIV) infection were excluded. iMCD was identified using 3 approaches:
1) Minor criteria approach: an iteration of the previously published claims-based algorithm adapted from the iMCD diagnostic criteria where HIV-/HHV-8- patients with the CD-specific ICD-10-CM code must also have at least 2 of the 11 minor diagnostic criteria, one of which was laboratory based2.
2) Treatment approach: HIV-/HHV-8- patients with the CD-specific ICD-10-CM code and an accompanying claim for either siltuximab or rituximab at any time following their index date.
3) Combination approach: HIV-/HHV-8- patients with the CD-specific ICD-10-CM code and identified by either the minor criteria approach or the treatment approach.
Patients with potential CD mimics (rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, lymphoma, and myeloma) identified by at least two claims for those mimics within 12 months post-index were excluded.
Results : There were 816 HIV-/HHV-8- patients with a CD diagnosis in the initial pool. Of these, 210 (26%) were identified as potential iMCD patients using a 120-day window for blood abnormalities and constitutional symptoms, and the full study period for all other criteria (approach #1) Using the treatment approach, 96 (12%) were identified as potential iMCD patients by meeting the treatment requirement (approach #2). Combined, 251 (31%) potential iMCD patients were identified by either the minor criteria or the treatment requirement (approach #3). Of the 251 potential iMCD patients meeting either treatment or minor criteria, 155/251 (62%) were defined by minor criteria only, 41/251 (16%) were identified by treatment only, and 55/251 (22%) met both minor and treatment criteria. After exclusion of patients with CD mimics consistent with international diagnostic criteria2, 186 iMCD patients were eligible with a mean age of 49 years; 52% were male. Using all data available post-index, only 22% had a claim for siltuximab treatment. 16% of the 186 iMCD patients had a claim for rituximab treatment, which is recommended by the NCCN as an alternative therapy.
Conclusions: Results from this analysis reveal 1) a discordance in the number of iMCD cases identified using different approaches, supporting the notion that using a health-claims dataset to study the epidemiology of iMCD is challenging, 2) an algorithm relying on use of the CD-specific ICD-10 code in conjunction with the minor criteria consistent with international diagnostic guidelines2 and exclusion of CD mimics likely provides the most accurate pool of iMCD patients, 3) siltuximab use was dismally low at 22%, indicating high unmet treatment need and 4) the use of a non-FDA approved therapy rituximab was observed in 16%, indicating divergence from clinical guidelines in routine clinical practice.
References: Mukherjee S, Martin R, Sande B, et al. Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6-directed therapy. Blood Adv. 2022 Jan 25;6(2):359-367. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017 Mar 23;129(12):1646-1657.