Use of a claims database to characterize and estimate the incidence rate for Castleman disease

Figures & data

Table I. Diagnostic criteria for Castleman disease.

Criterion	Rationale for criterion
Patients must have a diagnosis of enlargement of lymph nodes, ICD-9 code 785.6	CD is a lymphoproliferative disorder that leads to enlargement of lymph nodes
Patients must have continuous enrollment of 1 year prior to and 2 years after the IDD, with enlargement of lymph nodes	To allow a sufficient time period for identification of additional critical inclusion and exclusion criteria
Patients must have had lymph node biopsy within the 2-year follow-up period	A diagnosis of CD is usually not considered until its characteristic features are noted on an excision lymph node biopsy (CPT-4 code 38505); hence, this additional eligibility condition within 2 years of index date was required [3]
Patients should not have any of the following comorbidities in the 1 year prior to IDD: RA, lupus, cancer (including lymphoma) and HIV	Patients with lymph node histology consistent with CD should first have other causes of similar-appearing reactive lymphadenopathy ruled out; patients with a recent history of comorbidities associated with lymphadenopathy in the 1 year prior to the index date were excluded
Patients should not have any of the following comorbidities in the 1 year post-IDD: RA, lupus, cancer and HIV; or have developed NHL/HD in the second year post-IDD	To accurately and conservatively identify patients with a potential diagnosis of CD, while ruling out other diseases, those with a comorbidity associated with lymphadenopathy in the 1 year post-IDD were excluded

CD, Castleman disease; ICD-9, International Classification of Diseases, Ninth revision; CPT-4, Current Procedural Terminology; IDD, index diagnosis date; RA, rheumatoid arthritis; HIV, human immunodeficiency virus; NHL, non-Hodgkin lymphoma; HD, Hodgkin disease.

Table II. Distribution of potential patients with CD exposed to treatment.*

	IMS LifeLink™		MarketScan^®
Treatment	n	%	n	%
Doxorubicin	3	0.3	3	0.2
Dexamethasone	120	10.6	152	12.3
Prednisone	178	15.7	170	13.7
Rituximab	1	0.1	1	0.1

CD, Castleman disease.

*Other treatments evaluated included thalidomide, cyclophosphamide and tocilizumab, but no patients were identified in either database.

Figure 1. Algorithm used to identify potential Castleman disease (CD) and multicentric CD (MCD) cohorts in (a) IMS LifeLink™ and (b) MarketScan^® databases. Patients were also checked for histiocytosis or post-transplant lymphoproliferative disorder within 6 months of index diagnosis date (IDD) to exclude other confounding factors; no patient was found with these indications.

Table III. Patients excluded from cohort 1.

	IMS LifeLink™		MarketScan^®
	Count: occurrence	%	Count: occurrence	%
NHL	254	12.1	295	12.9
Hodgkin	8	0.4	23	1.0
RA	7	0.3	10	0.4
Lupus	5	0.2	10	0.4
Other cancers	325	15.5	374	16.3
HIV	3	0.1	16	0.7
Combination (of above)	384	18.3	365	16.0
No occurrence	1131	54.0	1240	54.2

NHL, non-Hodgkin lymphoma; RA, rheumatoid arthritis; HIV, human immunodeficiency virus.

Figure 2. Age distribution of CD cohort identified using the (a) IMS LifeLink™ and (b) MarketScan^® databases. In the IMS LifeLink™ database, N = 1129 as two patients were not included due to non-availability of data. In the MarketScan^® database, N = 1240 patients.

Table IV. Mean and median age of potential patients with CD.

	Age at first CD diagnosis
	IMS LifeLink™			MarketScan^®
	n	Mean, years (SD)	Median, years	n	Mean, years (SD)	Median, years
All	1129*	42.9 (17.6)	44	1240	45.8 (17.2)	48
Male	404	41.0 (18.9)	43	474	44.0 (18.6)	47
Female	725	43.9 (16.7)	45	766	47.0 (16.1)	48

CD, Castleman disease; SD, standard deviation.

*Two patients were not included due to non-availability of data.

Table V. Mean and median age of potential patients with MCD.

	Age at first CD diagnosis
	IMS LifeLink™			MarketScan^®
	n	Mean, years (SD)	Median, years	n	Mean, years (SD)	Median, years
All	273	44.3 (15.5)	46	283	49.6 (15.4)	51
Male	89	45.2 (17.3)	48	94	49.0 (17.6)	52
Female	184	43.9 (14.6)	45	189	49.8 (14.3)	51

MCD, multicentric Castleman disease; CD, Castleman disease; SD, standard deviation.

Table VI. Estimated incidence rate of CD and MCD.

	IMS LifeLink™		MarketScan^®
	Incidence rate (per million person-years)	Annual incidence (no. of cases)	Incidence rate (per million person-years)	Annual incidence (no. of cases)
CD	21.0	6502	24.8	7696
UCD	15.9	4932	19.1	5940
MCD	5.1	1569	5.7	1756

CD, Castleman disease; MCD, multicentric Castleman disease; UCD, unicentric Castleman disease.

Table VII. POEMS-related comorbidities associated with potential patients with CD based on IMS LifeLink™ database.

POEMS-related comorbidities	6 months pre-IDD (n = 1131)	6 months post-IDD (n = 1131)	p-value
Acute lymphadenitis	36	67	< 0.002
Thyroid-related disorders*	42	84	< 0.001
Chronic lymphadenitis	6	67	< 0.001
Hemangioma of other sites	0	3	0.084
Nonspecific mesenteric lymphadenitis	1	5	0.101
Peripheral neuropathy	8	15	0.142
Other diseases of the spleen	0	2	0.159
Unspecified disorder of the adrenal glands	2	0	0.159
Other non-infectious disorders of the lymphatic channels	0	2	0.159
Unspecified non-infectious disorder of the lymphatic channels	0	2	0.159
Hypocalcemia	0	2	0.159
Corticoadrenal insufficiency	0	2	0.159
Hemangioma of skin and subcutaneous tissue	1	4	0.180
Alopecia, unspecified	6	11	0.222
Unspecified pleural effusion	8	13	0.271
Splenomegaly	10	15	0.313

POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin syndrome; CD, Castleman disease; IDD, index diagnosis date.

*Includes unspecified non-toxic nodular goiter, non-toxic multinodular goiter, non-toxic uninodular goiter, benign neoplasm of the thyroid glands and other specified and unspecified disorders of the thyroid.

Table VIII. Other comorbidities (not related to POEMS) associated with potential patients with CD based on the IMS LifeLink™ database.

Other comorbidities (not related to POEMS)	6 months pre-IDD (n = 1131)	6 months post-IDD (n = 1131)	p-value
Swelling, mass or lump in head and neck	148	433	<0.001
Salivary gland–related disorders*	29	132	<0.001
Cough	77	120	<0.001
Neoplasm of uncertain behavior of other specified sites	10	51	<0.001
Sarcoidosis	6	37	<0.001
Neoplasm, of an unspecified nature, of other specified sites	5	37	<0.001
Chronic maxillary sinusitis	9	28	<0.002
Neoplasm, of an unspecified nature, of the digestive system	2	34	<0.001
Benign neoplasm of other specified sites	3	30	<0.001
Cellulitis and abscess of the neck	7	30	<0.001
Other non-specific, abnormal histological findings	1	24	<0.001
Hypertrophy of tonsils alone	5	21	<0.002
Other voice and resonance disorders	5	22	<0.001
Lipoma of other skin and subcutaneous tissue	3	24	<0.001
Other benign neoplasm of connective and other soft tissue of the head, face and neck	2	18	<0.001
Branchial cleft cyst	2	20	<0.001
Neoplasm, of an uncertain behavior, of the lip, oral cavity and pharynx	1	14	<0.001
Lipoma of other specified sites	0	10	<0.002
Swelling, mass or lump in the chest	15	35	0.004
Localized superficial swelling, mass or lump	44	74	0.005
Neoplasm, of an unspecified nature, of the endocrine glands and other parts of the nervous system	1	6	0.059

POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin syndrome; CD, Castleman disease; IDD, index diagnosis date.

*Includes benign neoplasm of major salivary glands, sialoadenitis, neoplasm of uncertain behavior of the major salivary glands and other specified diseases of the salivary glands.

Table IX. Prevalence of comorbidities and systemic symptoms in 2-year post-IDD based on IMS LifeLink™ database.

	MCD (%)	UCD (%)	Total (%)	p-value*
Total number of patients	273	858	1131
Thrombocytopenia	4.0	1.3	1.9	0.004
Hepatosplenomegaly	9.9	4.2	5.6	< 0.001
Ascites	1.8	1.0	1.2	0.308
Edema	13.6	5.8	7.7	< 0.001
Pulmonary/pleural effusion	2.2	2.6	2.5	0.728
Pericardial effusion	0.7	0.7	0.7	0.952^†
Hypoalbuminemia	0.7	0.3	0.4	0.406^‡
Hypergammaglobulinemia	0.4	0.1	0.3	0.380^‡
Malaise/fatigue	39.6	20.7	25.3	< 0.0001
Abdominal pain	27.1	16.9	19.4	0.0001
Swelling in head and neck	46.5	42.3	43.3	0.197
Any of the above	83.9	66.1	71.0	< 0.0001

IDD, index diagnosis date; MCD, multicentric Castleman disease; UCD, unicentric Castleman disease.

*p-Value for comparison of MCD versus UCD cohorts.

^†25% of cells have expected counts < 5. Chi-square may not be a valid test.

^‡50% of cells have expected counts < 5. Chi-square may not be a valid test.

Table X. Drug classes prescribed to potential patients with CD based on IMS LifeLink™ database.

	From index diagnosis
Drug classes that see an increase	1 year pre-IDD (n = 1131) count	1 year post-IDD (n = 1131) count	p-value
Opioid combinations	258	461	<0.001
Cephalosporins, first generation	107	209	<0.001
Lincosamides	33	75	<0.001
Antihistamines, phenothiazines	30	56	0.004
Glucocorticosteroids	139	182	0.010
Otic anti-infectives	2	12	0.007
Penicillin combinations	130	170	0.013
Ophthalmic anti-infectives	34	53	0.083
Oil-soluble vitamins	6	16	0.033
Oxazolidinones	0	4	0.046
Ophthalmics, miscellaneous	23	38	0.026
Viral vaccines	1	6	0.051
Influenza agents	7	16	0.059
Anaphylaxis therapy agents	9	17	0.114
Local anesthetics, topical	9	17	0.114
Hematorheologic agents	0	3	0.084
Opioid agonists	55	74	0.085
Coumarin anticoagulants	21	32	0.126

CD, Castleman disease; IDD, index diagnosis date.

Table XI. Distribution of potential patients with CD with other comorbid conditions in second year of lymphadenopathy diagnosis.

	IMS LifeLink™		MarketScan^®
Comorbid condition	n	%	n	%
Cancer	46	4.1	54	4.4
Lupus	4	0.4	7	0.6
RA	10	0.9	5	0.4
HIV	4	0.4	4	0.3
Herpes (HHV-8)	0	0.0	0	0.0
Kaposi sarcoma	0	0.0	0	0.0

CD, Castleman disease; RA, rheumatoid arthritis; HIV, human immunodeficiency virus.

Casper C. The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol 2005;129:3–17.

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