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Background Chronic Graft-Versus-Host Disease (cGVHD) is a complication of hematopoietic cell transplantation (HCT). While the clinical outcomes of cGVHD are well documented, few studies have assessed its treatment practices in the real-world. The objectives of this study are to quantify the prevalence of cGVHD, to examine provider prescribing patterns, and to evaluate the healthcare cost and resource utilization (HCRU) in a real-world US cGVHD population. Methods This study analyzed de-identified claims from the Medicare FFS 5% sample for beneficiaries enrolled from 2013-2016 and Pharmetrics commercial 2013-2018 databases to identify cGVHD in allogenic HCT patients. cGVHD was identified based on ICD-9/10 diagnosis codes for cGVHD or unspecified GVHD with a first diagnosis >180 days post HCT, or subsequent unspecified GVHD diagnosis >12 months post index diagnosis. Chronic GVHD prevalence was estimated by calculating age-adjusted prevalence rates within the Medicare and Pharmetrics sample populations and applying rates to the total US patient subpopulations as determined by CMS and Census data. Prevalence estimates were based on the last complete year of both Medicare FFS and Pharmetrics data (2016). Longitudinal and Line of Therapy (LOT) analyses were based on data from 2013-2018. A new LOT was defined as starting with the addition of systemic therapy to a patient's cGVHD regimen, regardless of prior lines of therapy or prior treatment. Treatments that stopped and restarted within 60 days were considered continuous treatment. Healthcare costs were calculated by adding the inpatient, outpatient, and pharmacy insurer and beneficiary paid amounts for the commercially insured population. Total HCRU was assessed using the number of inpatient and outpatient visits following the initial cGVHD diagnosis. Results In 2016, the projected prevalence of cGVHD in the US based on the Medicare FFS and Pharmetrics commercial databases was 14,017 individual patients. Within 3 years post allogeneic HCT, 42% of patients developed cGVHD; 66% of cGVHD patients had a prior diagnosis of acute GVHD. The majority of cGVHD patients received at least one systemic therapy; 71% and 47% of cGVHD patients progressed to a second and third LOT, respectively (Table 1). Of patients that received a second and third LOT, the average time from diagnosis to the second and third LOT was approximately 7 months and 10 months, respectively. Over 80% of cGVHD patients received systemic corticosteroid therapy for the treatment of cGVHD within 12 months post diagnosis, and 41% of cGVHD patients were receiving a corticosteroid within the 30 days prior to diagnosis. Within the 12 months post cGVHD diagnosis, most patients received a corticosteroid or a corticosteroid combination as a first LOT (57%), which decreased slightly as patients progressed to second and third line of therapy (49% and 48%, respectively). A total of 25 unique therapeutic agents and over 150 combinations were used in second and third LOT. While newer agents, such as ibrutinib and ruxolitinib, are continuing to increase in utilization among cGVHD patients, these therapies are only used among 1% (ibrutinib) and 1-3% (ruxolitinib) of patients through their first three lines of therapy in the patients captured in Pharmetrics commercial database through June 2018. In the 12 months post diagnosis, cGVHD patients had an average of 21.0 GVHD-related inpatient and outpatient visits (2.8 inpatient and 18.2 outpatient visits). In 2016 the average total annual cost per commercially insured cGVHD patient was $291,357. Conclusion A significant proportion of allogenic HCT patients continue to develop cGVHD, and despite advances in the understanding of cGVHD, corticosteroids remain the mainstay of therapy. However, most cGVHD patients are not adequately managed with first line corticosteroids, and many patients are cycling through several therapies, likely in part due to lack of efficacy and toxicity associated with currently available treatments. Real-world utilization of systemic therapies is highly variable, particularly for patients who progress beyond the first LOT, which highlights the need for evidence-based treatment approaches. cGVHD is a highly burdensome complication of allogenic HCT, and safer, more effective treatments are needed as many patients are not currently well managed on available therapies. Disclosures Bachier: Viracyte: Consultancy; Kadmon Corporation, LLC: Consultancy; Sanofi: Speakers Bureau. Aggarwal:Kadmon Corporation, LLC: Employment, Equity Ownership. Hennegan:Kadmon Corporation, LLC: Consultancy. Milgroom:Kadmon Corporation, LLC: Consultancy. Francis:Kadmon Corporation, LLC: Consultancy. Rotta:Jazz: Speakers Bureau; Kadmon Corporation, LLC: Consultancy.

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Background: Chronic Graft-Versus-Host Disease (cGVHD) is a common and potentially fatal complication after allogeneic hematopoietic stem cell transplantation. Beyond corticosteroids, there are multiple potential treatment options, including ibrutinib and ruxolitinib (off-label). Both ibrutinib and ruxolitinib are associated with adverse events (AEs) that may limit adherence or lead to treatment discontinuation. This retrospective analysis of United States administrative claims data examined ibrutinib and ruxolitinib use in cGVHD patients, including persistence on treatment, cost of care, and healthcare resource utilization (HCRU). Methods: Adult (≥18 years old) patients were identified in IQVIA™ Health Plan Claims Data (1/2014-9/2019) by ≥1 diagnosis claim for cGVHD by ICD-9 (279.51) and ICD-10 (D89.811) codes. The ibrutinib and ruxolitinib cohorts required ≥1 prescription claim (with the first claim as a proxy for treatment initiation = index) for the drug of interest, and no claims for the other drug (i.e., ruxolitinib or ibrutinib) within 12 months post index. Control cohorts required ≥1 prescription or treatment claim (index) for calcineurin inhibitors, mTOR inhibitors, mycophenolate mofetil, imatinib, methotrexate, etanercept, rituximab, or extracorporeal photopheresis, and no ibrutinib or ruxolitinib claim within 12 months post index. Propensity score matching (PSM) analyses required medical and drug benefit continuous enrollment for ≥6 months prior to index and ≥12 months after. Treatment persistence was assessed by Kaplan-Meier methodology, with a 30-day permissible gap between treatments, and AEs reported within 30 days of discontinuation were reported. In addition to individual AEs, composite measures of infections and lung AEs were assembled from ICD diagnosis codes. PSM of the ibrutinib and ruxolitinib cohorts to controls used age, sex, baseline cost, region, comorbidities, and lung involvement. PSM ensured patients will share similar characteristics, and outcome comparisons between these matched cohorts will not be confounded by the covariates used in the matching process. Costs and HCRU were assessed in the 12-month post index period. Results: In discontinuation analyses, 117 ibrutinib and 266 ruxolitinib patients were identified. In the year after index, 58/117 (50%) of ibrutinib and 109/266 (41%) of ruxolitinib patients discontinued (Figure 1). Within 30 days of discontinuation, AEs reported in the ibrutinib cohort in ≥10% of patients included (in decreasing order) the infection composite AE (36%), the lung composite AE (34%), dyspnea (28%), kidney failure (24%), edema (16%), atrial fibrillation (12%), thrombocytopenia (12%), and neutropenia (10%). In the ruxolitinib cohort, AEs reported within 30 days of discontinuation and occurring in ≥10% of patients included (in decreasing order) the infection composite AE (45%), the lung composite AE (37%), dyspnea (34%), thrombocytopenia (31%), edema (27%), kidney failure (27%), hypokalemia (15%), neutropenia (14%), thrombosis (13%), and hemorrhage (11%). In analyses of PSM cohorts, 39 ibrutinib patients matched to 110 control patients, and 81 ruxolitinib patients matched to 187 control patients. Annualized costs for the ibrutinib (median $263,658) and ruxolitinib (median $223,564) cohorts were significantly greater than control cohorts (p<0.001). Costs excluding the treatment of interest were greater for ibrutinib (median $82,989 vs. $64,546; p=0.25) and ruxolitinib (median $66,824 vs. $48,673; p=0.033). Ibrutinib patients showed a greater hospitalization rate versus control patients (24/39, 62% vs. 49/110, 45%; p=0.093). Ruxolitinib patients showed increased mean healthcare visits versus control patients (65.6 vs. 52.6; p=0.034). Conclusions: In this analysis, ibrutinib and ruxolitinib discontinuation and AEs previously reported to be associated with either ibrutinib or ruxolitinib utilization occurred in a similar temporal window. Ibrutinib and ruxolitinib patients also demonstrated higher treatment costs and increased healthcare visits versus control cGVHD patients. Further research is required to better understand the cost of cGVHD treatment with these medications. Sponsorship: Kadmon Corporation, LLC Disclosures Bachier: Sanofi: Speakers Bureau; AlloVir: Honoraria; CRISPR: Honoraria; Juno Therapeutics, a Bristol-Myers Squibb Company: Honoraria. Eiznhamer:Kadmon Corporation, LLC: Current Employment, Current equity holder in publicly-traded company. Milgroom:Trinity Life Sciences: Current Employment. Lenco:Trinity Life Sciences: Current Employment. Patel:Trinity Life Sciences: Current Employment. Skaar:Trinity Life Sciences: Current Employment. OffLabel Disclosure: ruxolitinib for chronic graft versus host disease

Introduction: Gout is a common comorbidity among solid organ transplantation patients and is usually attributed to the use of cyclosporine. This study aims to evaluate the prevalence of gout among solid organ transplantation patients to determine the prevalence in the tacrolimus era. Research Questions: To what degree is cyclosporine still used among prevalent solid organ transplantation patients? How prevalent is gout in the solid organ transplantation population not being treated by cyclosporine? Methods: Immunosuppressant regimens and gout prevalence among prevalent solid organ transplantation patients were assessed using retrospective claims data for a representative sample of commercially insured patients. For comparison to the prevalent solid organ transplantation population, immunosuppressant use at time of transplantation was compiled from published reports. Results: Between 2012 and 2016, the use of cyclosporine declined while use of tacrolimus increased, with greater cyclosporine use among prevalent versus incident solid organ transplantation patients. The prevalence of gout was 18.3%, 9.3%, and 9.1% for solid organ transplantation patients on cyclosporine, tacrolimus, and neither, respectively. Among all solid organ transplantation patients with gout, 66.6% and 21.5% were on tacrolimus versus cyclosporine. The prevalence of gout among noncyclosporine solid organ transplantation patients was significantly higher than in the general population without solid organ transplantation. Discussion: Despite declining cyclosporine use, gout prevalence remains high, with the majority of patients with gout receiving tacrolimus rather than cyclosporine. In summary, gout remains a frequent comorbidity of solid organ transplantation.