Burden of Illness of Aggressive Systemic Mastocytosis (ASM)

Per the 2008 WHO report on the spectrum of mast cell disease, ASM is a severe and debilitating form that may progress to mast cell leukemia. Very little has been published on the epidemiology and burden of ASM. This study reviewed the epidemiologic, clinical, humanistic and economic literature on ASM in order to estimate the burden of ASM in the US.

A systematic literature review was conducted in PubMed to identify publications regarding ASM published in English from 2000 to 2011. Data relevant to the burden of ASM were abstracted. 181 citations were identified in PubMed. 156 abstracts were screened and 6 articles were abstracted. An Excel model was developed to estimate the population-level burden of ASM in the US. Direct costs of treatment were calculated based on treatment patterns described in publications identified in the literature review. Indirect costs were not included in this analysis.

Mastocytosis is a hematopoietic stem cell disorder with pathological mast cell proliferation in tissues. Bone marrow, liver, spleen, gastrointestinal tract, and musculoskeletal systems are most often involved in ASM, and release of various mediators results in symptoms/conditions which can be severe or even debilitating, including anaphylaxis and allergic reactions, osteoporosis, hepatomegaly, splenomegaly, peptic ulcers, ascites, nausea/vomiting, diarrhea, fatigue, and weight loss. Treatment of ASM focuses on symptom reduction with antihistamines, bisphosphonates, glucocorticoids, proton pump inhibitors and mast cell stabilizers. Medications used to control the disease include interferon-alpha, cladribine (2CdA), hydroxyurea, and imatinib or investigational agents in clinical trials.

Two studies examining the burden of ASM on patient quality of life or productivity were identified. In one study, (Hermine O et al., PLoS ONE 2008; 3(5): e2266) 82% of systemic mastocytosis (SM) patients stated they suffer from a disability, with 28% reporting it as severe or intolerable. A recently published study (Nowak A et al., JDDG 2011; 9: 525–532) reported 64% of mastocytosis patients commented that the disease moderately to severely restricted their quality of life.

No publications were found in the literature search that provided estimates of the annual incidence or prevalence of ASM in the US. The annual prevalence of ASM was calculated using an Orphanet estimate for the global prevalence rate of 0.2 cases per 100,000 individuals multiplied by age- and gender-specific US Census population projections. The annual prevalence of ASM in the US was estimated at 428 patients age ≥20 years in 2010. An annual incidence estimate for the US was calculated by multiplying age- and gender-specific US Census population projections by an assumption of the percentage of SM patients with ASM based on a retrospective cohort study of patients with SM and a published estimate for the incidence rate of SM in the US. Using this method, the annual incidence of ASM was estimated at 77 patients ≥ age 20 in the US in 2010, with an incidence rate of 0.036 cases/100,000 individuals. In a published study of a large cohort of patients with SM, the median age of ASM patients was 65 years vs. 57 years for all SM patients. The median survival for ASM patients was 41 months vs. 63 months for all SM patients.

No studies were identified that examined the economic burden of ASM. Direct costs were estimated to be between $5,315 and $8,741 per patient per month. The majority of direct costs were associated with medications; while this is consistent with treatment based on symptom alleviation, it is also due to the fact that the publications used for estimation provided limited information on resource utilization, especially outpatient and ER visits, and as such resource utilization is likely underestimated.

These results provide preliminary estimates for the economic burden of ASM in the US. Additional research can assist in further quantifying healthcare resource utilization in ASM, especially ASM-related ER and outpatient visits. Due to the variety of symptoms experienced by ASM patients, the lack of a curative therapy, and shorter survival, it is likely that patients with ASM experience indirect costs (e.g., limitations in functioning or productivity) that may exceed the direct costs of treatment, and further evaluation is warranted.

Sotak:Novartis: Research Funding. Marin:Novartis: Research Funding. Coombs:Novartis: Employment. Teitelbaum:Novartis: Research Funding.