Abstract
Introduction:Idiopathic multicentric Castleman disease (iMCD) is a rare, cytokine-driven hematologic disorder characterized by diffuse lymphadenopathy and systemic inflammation. Prior studies have suggested increased rates of hematologic abnormalities and organ dysfunction in iMCD; however, the broader comorbidity burden and its economic impact remain poorly understood due to diagnostic challenges associated with accurate identification of true iMCD patients. The objectives of the current analyses were to quantify the prevalence of specific morbidities and associated healthcare costs amongst patients with iMCD relative to matched controls using real-world data.
Methods:A retrospective study using data from the Merative™ MarketScan® Databases was analyzed for the period 1/1/2016 - 6/30/2024. Patients with iMCD were identified as individuals with ≥1 claim for Castleman disease (CD; ICD-10-CM D47.Z2) and who met a previously reported algorithm incorporating diagnostic or treatment-based criteria. [1,2] The index date of diagnosis was defined as the earliest claim for CD. Non-iMCD controls were individuals without a claim for CD or lymphadenopathy in the same period and were assigned index dates (such that the distribution of years was similar to iMCD cases).In both cohorts, patients had uninterrupted medical and pharmacy benefits for >6 months pre-index (baseline) and at least 30 days of follow-up. Follow-up continued until the earliest of disenrollment or study end (6/30/2024). To minimize confounding, iMCD cases were matched to controls (1:3) using propensity score matching (nearest neighbor; 0.25 caliper) based on demographics and the Charlson Comorbidity Index (CCI).
Prevalence of specific morbidities was computed per 1,000 person-years (PY) during follow-up, including anemia, thrombocytopenia, drug-induced diabetes, extremity deep vein thrombosis, heart failure, liver dysfunction, portal vein thrombosis, pulmonary embolism, renal dysfunction, respiratory dysfunction or interstitial lung disease (ILD), stroke, and transient ischemic attack. The rate ratio with corresponding 95% confidence intervals (CIs) was also calculated to compare iMCD and control cohorts. Morbidity-related costs were assessed per-patient-per-month (PPPM), inflated to 2024 U.S. dollars, and compared between cases and controls. A standardized mean difference (SMD) of <0.10 was used to assess balance post-matching.
Results:After all inclusion and exclusion criteria were applied, 140 iMCD cases were matched to 420 controls (mean age 49 years; 52% female; 84% Commercially insured [SMD 0.00-0.01]). Post-matching, the mean CCI score was 1.9 and 2.0 [SMD 0.02] and mean (standard deviation [SD]) follow-up duration was 29.4 [25.2] and 27.2 [22.9] months for cases and controls, respectively. During the follow-up period, the prevalence of any morbidity was 1,124.9 per 1,000 PY among iMCD cases and 162.9 per 1,000 PY among non-iMCD controls, corresponding to a rate ratio of 6.91 [95% CI 6.65, 7.16]. Amongst the iMCD cohort, the morbidities with the highest prevalences were anemia (516.2 per 1,000 PY), renal dysfunction (230.6 per 1,000 PY), and respiratory dysfunction or ILD (159.5 per 1,000 PY). Rate ratios were highest for thrombocytopenia (9.91 [9.22, 10.59]), anemia (6.41 [6.09, 6.73]), and respiratory dysfunction or ILD (5.49 [5.00, 5.98]).
The total mean [SD] morbidity-related costs in the follow-up period were $6,436 [$17,067] PPPM in the iMCD cohort compared with $846 [$6,400] PPPM in the control cohort (p<0.001). The highest morbidity-related costs in the iMCD cohort were for anemia (PPPM $2,022 [$5,180] vs. $511 [$5,805] for controls; p=0.006), respiratory dysfunction or ILD (PPPM $1,433 [$8,562] vs. $136 [$1,736]; p=0.003), and heart failure (PPPM $1,278 [$8,177] vs. $147 [$1,151]; p=0.006).
Conclusions:Findings from this study demonstrate 6.91-fold higher prevalence of morbidities in multiple clinical domains among patients with iMCD, resulting in morbidity-related costs that are 7.61-fold higher compared with controls. These findings underscore the importance of timely diagnosis and the implementation of targeted interventions to mitigate the clinical and economic burden of iMCD.
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