Real-world study of direct medical and indirect costs and time spent in healthcare in patients with chronic graft versus host disease

Abstract

Chronic graft versus host disease (cGVHD) is a debilitating and costly complication following haemopoietic stem cell transplantation (HSCT). This study describes the economic burden associated with cGVHD. Direct costs associated with specialised healthcare utilisation (inpatient admissions and outpatient visits), as well as indirect costs associated with sickness absence-associated productivity loss were estimated in patients who underwent allogeneic HSCT in Sweden between 2006 and 2015, linking population-based health and economic registers. To capture the period of chronic GVHD, patients were included who survived > 182 days post-HSCT (start of follow-up), and cGVHD was classified based on patient treatment records to correct for any diagnosis underreporting. Patients were classified as ‘non-cGVHD’ if they received no immunosuppressive treatment, ‘mild cGVHD’ if they received only systemic corticosteroid treatment or immunosuppressive treatment, or ‘moderate–severe cGVHD’ if they received extracorporeal photopheresis (ECP) only, corticosteroid treatment and immunosuppressive treatment, or systemic corticosteroid treatment and ECP treatments. Patients with moderate–severe cGVHD spent more time in healthcare, had higher healthcare resource costs and higher sickness absence-related productivity loss compared to patients with non- or mild cGVHD. The cumulative total costs during the first 3 years of follow-up were EUR 14,887,599, EUR 20,544,056, and EUR 47,811,835 for non-, mild, and moderate–severe groups, respectively. The long-term costs incurred with cGVHD following HSCT continue to be very high and significantly impacted by cGVHD severity. This study adds real-world health resource and economic insight relevant for policy-makers and healthcare providers when considering the clinical challenge of balancing immunosuppression to reduce cGVHD.

Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease

“…GvHD also has a significant impact on healthcare resource utilisation, with patients experiencing more and longer hospitalisations and incurring greater healthcare costs [39][40][41][42]. A study in the USA found significantly greater 1-year post-alloHSCT costs for patients with aGvHD compared to those without aGvHD ($466,720 vs. $263,568; P < 0.001), with inpatient care being the primary cost driver [43].…”

“…Mortality with GvHD Percentage of GvHD patients developing refractory GvHD aGvHD 39% with sibling donors [24] 12% grade II [25] 91% 100-day overall survival (OS) grade II [32] 16.2% aGvHD (5.3% without GvHD) [28] 36% grade II-IV steroidrefractory aGvHD [25] 59% with unrelated donors [24] 11-16% grade III-IV [25,31] 65% 100-day OS grade III-IV [32] 8-16% [35] 49% [25] 86% 1-year OS grade III-IV [33] 49% grade IV aGvHD 35% TRM (11% without cGvHD) [29] 31% all grades steroidrefractory [25] 37% [25] 8% grade 3 [25] 53% 3 years OS [26] 8-11% 3-year mortality [35] 45% 5 years OS [26] with moderate-to-severe cGvHD were approximately fourfold higher than for patients without cGvHD [41].…”

“…A study in the USA found significantly greater 1-year post-alloHSCT costs for patients with aGvHD compared to those without aGvHD ($466,720 vs. $263,568; P < 0.001), with inpatient care being the primary cost driver [ 43 ]. A Swedish real-world study found that the cumulative direct medical costs over 3 years post-alloHSCT for patients with moderate-to-severe cGvHD were approximately fourfold higher than for patients without cGvHD [ 41 ].…”

“…As GvHD severity increases, post-alloHSCT costs are significantly increased, for example, grade III versus grade IV aGvHD, P = 0.03 [ 41 , 44 ]. This may be because increasing severity indicates steroid-resistant GvHD.…”

Population-based real-world registry study to evaluate clinical outcomes of chronic graft-versus-host disease

“…To address this unmet need, we used national registers to perform a retrospective, population-based longitudinal study. Instead of the NIH method based on the presentation of cGVHD, we used our newly introduced method [14] that considered the timing and extent of the immunosuppressive treatment given to HSCT recipients, with the objectives to investigate the burden of disease (including mortality and morbidities) and healthcare utilization in Sweden.…”