Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6–directed therapy

Abstract

The epidemiology of HHV-8-negative/idiopathic multicentric Castleman disease (iMCD) remains incompletely understood. Prior epidemiologic studies of CD and iMCD have been hampered by difficulties in accurate case ascertainment due to lack of uniform diagnostic criteria and a disease-specific International Classification of Diseases (ICD) code. In this study, we provide reliable estimates of CD and iMCD in the US using a novel claims-based algorithm that includes CD specific ICD-10 diagnosis code (D47.Z2) supported by presence of ≥2 claims codes corresponding to the minor criteria from the international evidence-based diagnostic criteria for iMCD. We additionally analyzed the treatment classes and patterns in the clinical course of iMCD patients. Using an administrative claims database of 30.7 million individuals enrolled between January 1, 2017 and December 31, 2018, we identified 254 iMCD patients with an estimated annual incidence and prevalence of 3.4 (95% CI, 1.4 - 9.2) and 6.9 (95% CI, 3.7 - 13.3) cases per million, respectively. Among iMCD patients, 39% received corticosteroid monotherapy, 33.1% received no iMCD-directed treatment, and 9.8% received IL-6 targeted therapy with tocilizumab or siltuximab. Siltuximab, which is the only FDA-approved treatment and established first-line treatment recommendation, was used in only 8.7% of iMCD patients. This study provides the most up to date understanding of the iMCD disease burden in the US and identifies a major unmet treatment need for IL-6 directed therapy in this vulnerable cohort.

Comprehensive analysis of 65 patients with Castleman disease in a single center in China

“…Clinical trials towards siltuximab in iMCD patients were also actively performed to validate its long-term safety and activity as well as to find its predictive biomarkers of response 37 – 39 . However, currently, the anti-IL-6 therapy (siltuximab), is not widely applicable and does not benefit all patients with CD (nonresponders) 13 , 40 . Studies on alternative treatment approaches that can be adaptively used were also rigorously proceeded, such as the thalidomide-cyclophosphamide-prednisone (TCP) regimen, which proved to be an effective and safe treatment of newly diagnosed iMCD patients 41 .…”

“…Despite all this, the very nature of CD still remains unclear enough, especially the little published information about incidence from China. As a rare entity, CD received its first ICD-10 diagnosis code in October 2016, but overall standard diagnostic criteria are still needed to be improved, especially iMCD 12 . In this study, we retrospectively analyzed 65 patients in Henan Provincial People’s Hospital in central China for the better understanding of this disease.…”

Treatment and Outcome of Castleman Disease: A Retrospective Report of 31 Patients

“…To deepen the cognition of MCD, features of all 8 patients with MCD were comprehensively summarized ( Table 3 ). Siltuximab, the only approved and established first-line treatment for iMCD by the US Food and Drug Administration, 16 has not been approved for marketing in China during the study period. In this study, the primary therapies for 8 patients with MCD were steroids and chemotherapy with or without rituximab.…”

Drug discovery in spinal cord injury-induced osteoporosis: a text mining-based study

“…According to the druggene interaction, the potential drugs siltuximab (10.21, IL-6 inhibitor), olokizumab (10.21, IL-6 inhibitor), clazakizumab (7.66, IL-6 inhibitor) and BAN2401 (6.17, APP inhibitor) are likely to attenuate inflammation and prevent bone loss. Siltuximab is currently studied for the treatment of COVID-19 and idiopathic multicentric Castleman disease (46)(47)(48). olokizumab is used in clinical trials for the treatment of rheumatoid arthritis with a remarkable therapeutic effect (49,50).…”