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A Cost-Effectiveness Analysis Evaluating the Role of Fecal Calprotectin for Postoperative Surveillance after Surgical Resection for Crohn’s Disease
Figure 1. 2-way sensitivity analysis evaluating the effects of altering the cost of vedolizumab with the cost of adalimumab on the study outcome.
Su1899 A MARKOV MODEL EVALUATING THE COST-EFFECTIVENESS OF USTEKINUMAB COMPARED TO VEDOLIZUMAB FOR PATIENT'S WITH CROHN'S DISEASE AS THIRD-LINE THERAPY Yecheskel Schneider, Monica Saumoy, Shirley A. Cohen-Mekelburg, Stephanie Gold, Ellen Scherl, Adam F. Steinlauf QALY = Quality Adjusted Life Years; ICER = Incremental Cost Effectiveness Ratio; Dominated describes scenarios in which a strategy is less effective and more costly.
Background: Ustekinumab (UKM), an anti-interleukin 12/anti-interleukin 23 monoclonal antibody, has been recently approved for the treatment of Crohn's disease (CD). Ustekinumab is costly, and approval may be difficult to obtain from insurance companies without the initial use of anti-tumor necrosis factor (TNF) agents. This study sought to evaluate the cost-effectiveness of UKM versus vedolizumab (VDZ) as a third-line agent for patients with CD, who have previously failed two anti-TNFs. Methods: Utilizing a decision analytic Markov Model, we evaluated the most cost-effective approach for a 30-year old with moderatesevere CD who previously failed two anti-TNF agents. Two treatment pathways were compared: UKM or VDZ. Patients in each pathway could either achieve clinical remission, fail therapy (as primary or secondary failures), cross over to the other biologic, progress to surgery, or die. Patients could transition between health states in three-month cycles, and were followed over a five-year time horizon. Transitions and costs were taken from the published literature and available public sources, from a payers' perspective. Outcome measures were reported in incremental cost-effectiveness ratios (ICERs; 2016 US dollars per quality-adjusted life years [QALY] gained), with a willingness to pay (WTP) threshold set at $100,000/QALY. Results: In the base case analysis, ustekinumab was the preferred strategy. Although the vedolizumab arm resulted in both larger costs and larger number of QALYs, the ICER was well above our WTP threshold (Table 1). We performed one-way sensitivity analyses for all variables in the model, but none of the variables were significant. We also performed two-way sensitivity analyses testing different combinations of costs for VDZ and UKM, and varying probabilities of induced remission; for all tested combinations, UKM remained the preferred strategy. Conclusions: Our results show that UKM is more cost-effective than VDZ for patients with moderate-severe CD who previously failed two anti-TNF agents. This is important to note for insurance companies, as patients who are candidates for UKM, and have previously failed two anti-TNF agents, would greatly benefit from UKM. Further studies evaluating the cost-effectiveness of UKM as first and second line therapy are needed to better understand the optimal position of this therapy. Table 1: Results of base case analysis comparing ustekinumab to vedolizumab for patients with Crohn's Disease, as third line therapy
Su1901 EVALUATION OF PHARMACOKINETIC PROFILES OF SB2 AS A BIOSIMILAR OF REFERENCE INFLIXIMAB Donghoon Shin, Jung Won Kang, Sunghoon Park, Younju Lee, Sora Lee Background: Based on the totality of evidence with similar analytical, pharmacokinetic (PK) and clinical results, SB2 was approved by European Medicines Agency as a biosimilar of the reference infliximab (INF) for all indications for which INF has been approved. Here we report the PK profiles of SB2 compared to that of INF in two animal models, healthy subjects and patients with rheumatoid arthritis (RA). Methods: The pre-clinical PK profiles were evaluated in single and repeated dose studies (1, 3, and 10 mg/kg of SB2, European Union sourced INF [EU-INF] or United States sourced INF [US-INF]) in two animal models (Sprague Dawley [SD] rat and transgenic Tg197 mouse). The clinical Phase I pivotal study for PK was conducted in healthy subjects1. The subjects received a single 5 mg/kg intravenous infusion of study drugs (SB2, EU-INF or US-INF) and were observed for 10 weeks. PK equivalence was to be concluded if the 90% confidence interval (CI) for the ratio geometric least squares means (LSMeans) of the primary PK endpoints (area under the concentrationtime curve [AUC] from time zero to infinity [AUCinf], AUC from time zero to the last quantifiable concentration [AUClast] and maximum concentration [Cmax]) were within the standard equivalence margin of 0.8 to 1.25. The steady state PK profile was assessed in a Phase III study in RA patients2. In this study, the patients received 3 mg/kg of SB2 or EUINF at weeks 0, 2, 6 and then every 8 weeks up to 46 weeks. PK analyses were performed up to week 30. Infliximab serum concentration was measured through two different enzymelinked immunosorbent assays for pre-clinical and clinical studies. Results: In pre-clinical studies, available PK profiles from animal studies showed no significant differences in Cmax and AUClast between SB2, EU-INF and US-INF. In healthy subjects, the 90% CIs for the primary PK parameters were within the pre-defined equivalence margin of 0.8 to 1.25 between SB2 and reference products (SB2 vs. EU-INF and SB2 vs. US-INF). In RA patients, the mean trough level was comparable between SB2 (ranging from 1.915 to 17.965 to µg/ mL) and EU-INF (ranging from 2.224 to 16.954 to µg/mL) from week 2 to week 30. The PK profiles were also comparable between SB2 and INF when analysed by the presence of ADA in both Phase I and Phase III clinical studies. Conclusion: Similar PK profiles of SB2 and reference products were confirmed in pre-clinical and clinical studies. Altogether, the previously demonstrated analytical similarity and the data presented here indicate that similar PK are expected in all indications approved for SB2. Reference 1. Shin D et al. Biodrugs. 2015; 29:381-388 2. Choe J-Y et al. Ann Rheum Dis. 2015; 2015-207764
US = US Dollars; QALY = Quality Adjusted Life Years; ICER = Incremental Cost Effectiveness Ratio
Su1900 Su1902 A COST-EFFECTIVENESS ANALYSIS EVALUATING THE ROLE OF FECAL CALPROTECTIN FOR POSTOPERATIVE SURVEILLANCE AFTER SURGICAL RESECTION FOR CROHN'S DISEASE Gaurav Ghosh, Yecheskel Schneider, Nicole T. Shen, Monica Saumoy, Shirley A. CohenMekelburg, Ellen Scherl, Adam F. Steinlauf
STRUCTURE AND BIOLOGICAL ACTIVITY OF INFLIXIMAB PRODUCTS Changsoo Lee, Min Jeong, JongAh Lee, Saebom Seo, SungChun Cho, Wei Zhang, Orlando Jaquez Background: As biosimilars are entering the market, evaluation of the quality of these products is needed as differences in manufacturing process may lead to differences in critical quality attributes, which affect efficacy. Thus, major biological activities of reference infliximab and of two biosimilars (SB2 and CT-P13) were determined. Methods: More than 30 structural, physicochemical, and biological attributes of the infliximab products were
Background: Patients with Crohn's disease (CD) often experience recurrence after intestinal resection, and postoperative endoscopic monitoring has a role in early identification of endoscopic recurrence. A prospective clinical trial has shown that fecal calprotectin (FCP) can be predictive of disease recurrence for patient with CD after intestinal resection. Currently, there is limited data evaluating the most cost-effective approach for postoperative surveillance, incorporating the role of FCP. We assessed the cost-effectiveness of using FCP to inform
S-589
AGA Abstracts
AGA Abstracts
postoperative decision making in Crohn's disease patients. Methods: We developed a decision tree of postoperative Crohn's disease, to evaluate the hypothetical case of an individual who is status-post bowel resection and is undergoing surveillance for disease recurrence. We examined three competing strategies: 1) FCP, 2) FCP with confirmation by colonoscopy, and 3) colonoscopy alone. If a patient was positive for disease in any of the strategies, postoperative biologic was started, with the potential for ongoing remission or the development of recurrence. Patients could also develop complications of biologic therapy, including lymphoma or infection. Probabilities and costs were estimated from published literature and public sources. FCP sensitivity and specificity were estimated from the literature based on a cutoff of 100. We calculated clinical outcomes (quality adjusted life years [QALY]), cost (2015 US dollars), and incremental cost effectiveness ratios (ICERS; difference in cost/QALY), with a willingness to pay (WTP) threshold set at $100,000/QALY. Results: The results of our base case (Table 1) found that strategy 2 (FCP with confirmatory colonoscopy) was dominant (more effective and less costly) compared to FCP alone. The colonoscopy alone arm had an ICER of $498,900/QALY (which is above our WTP threshold), compared to FCP with confirmatory colonoscopy. A Tornado diagram and one-way sensitivity analysis for all variables did not show that the model was affected by any one variable. Conclusions: The most cost-effective approach for postoperative surveillance in patients with CD is one that incorporates FCP with confirmatory colonoscopy. As the American healthcare system increases its focus on cost-conscious care, the role of FCP in the management of patients with CD may play a greater role in predicting disease, particularly in the post-operative setting. Table 1. Cost-effectiveness results comparing different strategies incorporating fecal calprotectin for monitoring of postoperative recurrence in patients with Crohn's disease
Su1899 A MARKOV MODEL EVALUATING THE COST-EFFECTIVENESS OF USTEKINUMAB COMPARED TO VEDOLIZUMAB FOR PATIENT'S WITH CROHN'S DISEASE AS THIRD-LINE THERAPY Yecheskel Schneider, Monica Saumoy, Shirley A. Cohen-Mekelburg, Stephanie Gold, Ellen Scherl, Adam F. Steinlauf QALY = Quality Adjusted Life Years; ICER = Incremental Cost Effectiveness Ratio; Dominated describes scenarios in which a strategy is less effective and more costly.
Background: Ustekinumab (UKM), an anti-interleukin 12/anti-interleukin 23 monoclonal antibody, has been recently approved for the treatment of Crohn's disease (CD). Ustekinumab is costly, and approval may be difficult to obtain from insurance companies without the initial use of anti-tumor necrosis factor (TNF) agents. This study sought to evaluate the cost-effectiveness of UKM versus vedolizumab (VDZ) as a third-line agent for patients with CD, who have previously failed two anti-TNFs. Methods: Utilizing a decision analytic Markov Model, we evaluated the most cost-effective approach for a 30-year old with moderatesevere CD who previously failed two anti-TNF agents. Two treatment pathways were compared: UKM or VDZ. Patients in each pathway could either achieve clinical remission, fail therapy (as primary or secondary failures), cross over to the other biologic, progress to surgery, or die. Patients could transition between health states in three-month cycles, and were followed over a five-year time horizon. Transitions and costs were taken from the published literature and available public sources, from a payers' perspective. Outcome measures were reported in incremental cost-effectiveness ratios (ICERs; 2016 US dollars per quality-adjusted life years [QALY] gained), with a willingness to pay (WTP) threshold set at $100,000/QALY. Results: In the base case analysis, ustekinumab was the preferred strategy. Although the vedolizumab arm resulted in both larger costs and larger number of QALYs, the ICER was well above our WTP threshold (Table 1). We performed one-way sensitivity analyses for all variables in the model, but none of the variables were significant. We also performed two-way sensitivity analyses testing different combinations of costs for VDZ and UKM, and varying probabilities of induced remission; for all tested combinations, UKM remained the preferred strategy. Conclusions: Our results show that UKM is more cost-effective than VDZ for patients with moderate-severe CD who previously failed two anti-TNF agents. This is important to note for insurance companies, as patients who are candidates for UKM, and have previously failed two anti-TNF agents, would greatly benefit from UKM. Further studies evaluating the cost-effectiveness of UKM as first and second line therapy are needed to better understand the optimal position of this therapy. Table 1: Results of base case analysis comparing ustekinumab to vedolizumab for patients with Crohn's Disease, as third line therapy
Su1901 EVALUATION OF PHARMACOKINETIC PROFILES OF SB2 AS A BIOSIMILAR OF REFERENCE INFLIXIMAB Donghoon Shin, Jung Won Kang, Sunghoon Park, Younju Lee, Sora Lee Background: Based on the totality of evidence with similar analytical, pharmacokinetic (PK) and clinical results, SB2 was approved by European Medicines Agency as a biosimilar of the reference infliximab (INF) for all indications for which INF has been approved. Here we report the PK profiles of SB2 compared to that of INF in two animal models, healthy subjects and patients with rheumatoid arthritis (RA). Methods: The pre-clinical PK profiles were evaluated in single and repeated dose studies (1, 3, and 10 mg/kg of SB2, European Union sourced INF [EU-INF] or United States sourced INF [US-INF]) in two animal models (Sprague Dawley [SD] rat and transgenic Tg197 mouse). The clinical Phase I pivotal study for PK was conducted in healthy subjects1. The subjects received a single 5 mg/kg intravenous infusion of study drugs (SB2, EU-INF or US-INF) and were observed for 10 weeks. PK equivalence was to be concluded if the 90% confidence interval (CI) for the ratio geometric least squares means (LSMeans) of the primary PK endpoints (area under the concentrationtime curve [AUC] from time zero to infinity [AUCinf], AUC from time zero to the last quantifiable concentration [AUClast] and maximum concentration [Cmax]) were within the standard equivalence margin of 0.8 to 1.25. The steady state PK profile was assessed in a Phase III study in RA patients2. In this study, the patients received 3 mg/kg of SB2 or EUINF at weeks 0, 2, 6 and then every 8 weeks up to 46 weeks. PK analyses were performed up to week 30. Infliximab serum concentration was measured through two different enzymelinked immunosorbent assays for pre-clinical and clinical studies. Results: In pre-clinical studies, available PK profiles from animal studies showed no significant differences in Cmax and AUClast between SB2, EU-INF and US-INF. In healthy subjects, the 90% CIs for the primary PK parameters were within the pre-defined equivalence margin of 0.8 to 1.25 between SB2 and reference products (SB2 vs. EU-INF and SB2 vs. US-INF). In RA patients, the mean trough level was comparable between SB2 (ranging from 1.915 to 17.965 to µg/ mL) and EU-INF (ranging from 2.224 to 16.954 to µg/mL) from week 2 to week 30. The PK profiles were also comparable between SB2 and INF when analysed by the presence of ADA in both Phase I and Phase III clinical studies. Conclusion: Similar PK profiles of SB2 and reference products were confirmed in pre-clinical and clinical studies. Altogether, the previously demonstrated analytical similarity and the data presented here indicate that similar PK are expected in all indications approved for SB2. Reference 1. Shin D et al. Biodrugs. 2015; 29:381-388 2. Choe J-Y et al. Ann Rheum Dis. 2015; 2015-207764
US = US Dollars; QALY = Quality Adjusted Life Years; ICER = Incremental Cost Effectiveness Ratio
Su1900 Su1902 A COST-EFFECTIVENESS ANALYSIS EVALUATING THE ROLE OF FECAL CALPROTECTIN FOR POSTOPERATIVE SURVEILLANCE AFTER SURGICAL RESECTION FOR CROHN'S DISEASE Gaurav Ghosh, Yecheskel Schneider, Nicole T. Shen, Monica Saumoy, Shirley A. CohenMekelburg, Ellen Scherl, Adam F. Steinlauf
STRUCTURE AND BIOLOGICAL ACTIVITY OF INFLIXIMAB PRODUCTS Changsoo Lee, Min Jeong, JongAh Lee, Saebom Seo, SungChun Cho, Wei Zhang, Orlando Jaquez Background: As biosimilars are entering the market, evaluation of the quality of these products is needed as differences in manufacturing process may lead to differences in critical quality attributes, which affect efficacy. Thus, major biological activities of reference infliximab and of two biosimilars (SB2 and CT-P13) were determined. Methods: More than 30 structural, physicochemical, and biological attributes of the infliximab products were
Background: Patients with Crohn's disease (CD) often experience recurrence after intestinal resection, and postoperative endoscopic monitoring has a role in early identification of endoscopic recurrence. A prospective clinical trial has shown that fecal calprotectin (FCP) can be predictive of disease recurrence for patient with CD after intestinal resection. Currently, there is limited data evaluating the most cost-effective approach for postoperative surveillance, incorporating the role of FCP. We assessed the cost-effectiveness of using FCP to inform
S-589
AGA Abstracts
AGA Abstracts
postoperative decision making in Crohn's disease patients. Methods: We developed a decision tree of postoperative Crohn's disease, to evaluate the hypothetical case of an individual who is status-post bowel resection and is undergoing surveillance for disease recurrence. We examined three competing strategies: 1) FCP, 2) FCP with confirmation by colonoscopy, and 3) colonoscopy alone. If a patient was positive for disease in any of the strategies, postoperative biologic was started, with the potential for ongoing remission or the development of recurrence. Patients could also develop complications of biologic therapy, including lymphoma or infection. Probabilities and costs were estimated from published literature and public sources. FCP sensitivity and specificity were estimated from the literature based on a cutoff of 100. We calculated clinical outcomes (quality adjusted life years [QALY]), cost (2015 US dollars), and incremental cost effectiveness ratios (ICERS; difference in cost/QALY), with a willingness to pay (WTP) threshold set at $100,000/QALY. Results: The results of our base case (Table 1) found that strategy 2 (FCP with confirmatory colonoscopy) was dominant (more effective and less costly) compared to FCP alone. The colonoscopy alone arm had an ICER of $498,900/QALY (which is above our WTP threshold), compared to FCP with confirmatory colonoscopy. A Tornado diagram and one-way sensitivity analysis for all variables did not show that the model was affected by any one variable. Conclusions: The most cost-effective approach for postoperative surveillance in patients with CD is one that incorporates FCP with confirmatory colonoscopy. As the American healthcare system increases its focus on cost-conscious care, the role of FCP in the management of patients with CD may play a greater role in predicting disease, particularly in the post-operative setting. Table 1. Cost-effectiveness results comparing different strategies incorporating fecal calprotectin for monitoring of postoperative recurrence in patients with Crohn's disease