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Long-Term Safety of Adalimumab in Patients with Crohn's Disease: Final Data from Pyramid Registry
616
EARLY INITIATION OF ANTI-TNF THERAPY IS COST-SAVING COMPARED TO LATE INITIATION FOR PATIENTS WITH CROHN'S DISEASE Candace L. Beilman, Erin Kirwin, Christopher Ma, Christopher McCabe, Richard N. Fedorak, Brendan P. Halloran
LONG-TERM SAFETY OF ADALIMUMAB IN PATIENTS WITH CROHN'S DISEASE: FINAL DATA FROM PYRAMID REGISTRY Geert R. D'Haens, Walter Reinisch, Jack Satsangi, Edward V. Loftus, Remo Panaccione, Gabriela Alperovich, Jasmina Kalabic, Mareike Bereswill, Dilek Arikan, Joel H. Petersson, Anne M. Robinson
Background: Anti-TNF therapies are effective for the induction and maintenance of remission in patients with Crohn's disease (CD), and are generally prescribed when patients fail to respond to conventional, less-costly medical therapies including steroids and immunomodulators. Our recent retrospective study showed that early initiation (within two years of diagnosis) of anti-TNF therapies reduced rates of surgery and loss of response requiring dose escalation. It is hypothesized that early initiation of anti-TNF therapy may minimize chronic, irreversible changes to the bowel, such as fibrosis, stenosis, and the formation of fistula. However, the cost-effectiveness of this strategy is unknown, given the expensive nature of these medications. Aims: The aim of this study was to determine the cost-effectiveness of early versus late initiation of anti-TNF therapy for the management of CD. Methods: A Markov model was constructed to simulate the progression of a hypothetical cohort of patients with CD after the initiation of either infliximab or adalimumab. Using this model, we compared the lifetime cost-effectiveness of early (≤2 years after diagnosis) versus late (>2 years after diagnosis) initiation of anti-TNF therapy using published loss of response rates. Transition probabilities were determined through a literature search, giving priority to randomized controlled trials with large sample sizes, followed by observational studies if needed. Health state costs were obtained from the Alberta Ministry of Health by linking inpatient, ambulatory, and physician claim databases. Utility scores were obtained from published literature using the Standard Gamble Approach. Deterministic and probabilistic sensitivity analysis was used to characterize uncertainty related to input parameters. Costs and outcomes were discounted at a rate of 5% per year. Results: Over a patient's lifetime, early initiation of infliximab yielded an additional 1.02 quality-adjusted life years (QALYs) and saved $18,054 compared to late initiation of infliximab. Early initiation of adalimumab yielded an additional 0.74 QALYs and saved $18,526 compared to late initiation of adalimumab. At a willingness-to-pay threshold of $50,000 per QALY, early initiation of both infliximab and adalimumab had a 68% chance of being cost-effective, while late initiation had a 32% chance of being cost-effective. Conclusions: Based on our current model, early initiation of either infliximab or adalimumab is cost-saving and dominates late initiation for patients with CD. Sensitivity analysis revealed these results were robust. The results of this study may serve to support early treatment with anti-TNF therapy from both a cost and patient outcome perspective.
Background: The final top-line results of the long-term safety of ADA assessed in patients (pts) with moderately and severely active Crohn's disease (CD) treated in routine clinical practice and enrolled in the global postmarketing observational registry PYRAMID are presented. The primary objective was to rule out a doubled risk of lymphoma for pts treated with ADA compared with the expected background lymphoma rate. Methods: Pts who were newly prescribed ADA or currently receiving ADA according to the local product label were enrolled in the registry and followed for up to 6 years. Adverse events (AEs), serious AEs (SAEs), AEs of special interest, and AEs leading to drug discontinuation were collected. Registry treatment-emergent AEs (TEAE; any event with onset on/after first dose of ADA until 70 days after last ADA injection) and observational AEs (any event occurring from first dose of ADA until last contact) were collected. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 and reported as events/100 patient-years (PY). Results: A total of 5025 pts were evaluated in this analysis (57.1% female, mean age 37.8 yrs at enrollment), representing 16680.4 PYs of ADA exposure over 6 yrs. The mean (SD) duration of ADA exposure during the registry was 1212.4 (835.4) days. A total of 2852 pts (56.8%) had prior biologic use, 1798 (35.8%) used immunomodulators (IMM), and 1463 (29.1%) used corticosteroids (CS) at registry baseline (BL). Overall, 3478 (69.2%) pts discontinued ADA or the registry. A total of 1853 pts (36.9%) reported 4129 treatmentemergent SAEs (24.8/100 PY) (Table). A total of 556 pts reported 792 treatment-emergent serious infections (SI) (4.7/100 PY). The only treatment-emergent SI reported by ≥1% of pts was perianal abscess (0.7/100 PY). The SI rate was higher for pts with concomitant medication at BL (ADA+CS, ADA+IMM, ADA+CS+IMM) vs ADA monotherapy (6.4, 4.8, 5.0 vs 4.2/100PY, respectively). A total of 116 pts experienced 134 treatment-emergent malignancy events (0.8/100 PY), of which 10 were lymphomas. No non-treatment-emergent lymphoma events were reported. The registry exposure-adjusted rate of lymphoma was 0.060/100 PY. The upper bound of the 1-sided 95% CI of this rate was 0.102/100 PYs and fell below 0.168/100 PYs (double the expected rate of 0.084/100 PYs). TEAEs leading to death were reported in 43 pts (0.3/100 PY). Conclusions: The registry achieved the goal of ruling out a doubling of lymphoma risk in pts with CD treated with ADA. No new safety signals were identified.
617 DEFINING PATIENT-CENTERED OUTCOMES FOR IBD AND AN INTERNATIONAL, CROSS-DISCIPLINARY CONSENSUS Andrew H. Kim, Charlotte Roberts, Brian G. Feagan, Rupa Banerjee, Willem Bemelman, Keith Bodger, Marc Derieppe, Axel Dignass, Richard Driscoll, Ray Fitzpatrick, Peter D. Higgins, Paulo G. Kotze, Jillian Meissner, Marian O'Connor, Zhihua Ran, Corey A. Siegel, Helen Terry, Welmoed K. van Deen, Christien Janneke Van Der Woude, Alandra Weaver, Suk-Kyun Yang, Bruce E. Sands, Severine Vermeire, Simon P. Travis Background & Aims Value-based healthcare aims to achieve the best possible health outcomes for the lowest cost. Key to its success involves measuring outcomes that matter most to patients. Currently for inflammatory bowel disease (IBD), registries and clinical trials lack a unifying set of well-defined outcomes, making comparisons between populations difficult. Our goal was to develop a minimum Standard Set of patient-centered outcomes for IBD to provide a common language for outcomes that can be tracked systematically in a variety of healthcare settings. Methods An international, multidisciplinary working group (n=25) from 12 countries within Europe, North America, Asia, Australia, and South America representing patients, gastroenterologists, surgeons, specialist nurses, IBD registries, patientreported outcome measure (PROM) methodologists, and patient organisations participated in a series of teleconferences incorporating a modified Delphi process. Systematic review of existing literature, registry data, patient focus groups and open review periods were used to reach consensus on a minimum set of standard outcome measures, the best validated tools for measurement and baseline risk-adjustment variables. Results A minimum Standard Set of outcomes (Figure/Table 1), preferred tools and measurement frequency was defined by the Working Group for patients (aged >16) with IBD. Outcome domains included patient reported outcomes (including quality of life, symptom score, nutritional status and impact of fistulae); survival and disease control (survival, disease activity/remission, colorectal cancer, and anemia); disutility of care (treatment-related complications); and healthcare utilization (IBD-related admissions and emergency room visits), all measured at baseline and 6 or 12 month intervals. A single, accessible PROM (IBD-Control questionnaire) was recommended. A core set of patients' baseline characteristics including demographics, baseline clinical and
Model structure diagram representing the progression of a hypothetical cohort of patients with moderate to severe Crohn's disease after initiating either early or late anti-TNF therapy.
S-137
AGA Abstracts
AGA Abstracts
615
EARLY INITIATION OF ANTI-TNF THERAPY IS COST-SAVING COMPARED TO LATE INITIATION FOR PATIENTS WITH CROHN'S DISEASE Candace L. Beilman, Erin Kirwin, Christopher Ma, Christopher McCabe, Richard N. Fedorak, Brendan P. Halloran
LONG-TERM SAFETY OF ADALIMUMAB IN PATIENTS WITH CROHN'S DISEASE: FINAL DATA FROM PYRAMID REGISTRY Geert R. D'Haens, Walter Reinisch, Jack Satsangi, Edward V. Loftus, Remo Panaccione, Gabriela Alperovich, Jasmina Kalabic, Mareike Bereswill, Dilek Arikan, Joel H. Petersson, Anne M. Robinson
Background: Anti-TNF therapies are effective for the induction and maintenance of remission in patients with Crohn's disease (CD), and are generally prescribed when patients fail to respond to conventional, less-costly medical therapies including steroids and immunomodulators. Our recent retrospective study showed that early initiation (within two years of diagnosis) of anti-TNF therapies reduced rates of surgery and loss of response requiring dose escalation. It is hypothesized that early initiation of anti-TNF therapy may minimize chronic, irreversible changes to the bowel, such as fibrosis, stenosis, and the formation of fistula. However, the cost-effectiveness of this strategy is unknown, given the expensive nature of these medications. Aims: The aim of this study was to determine the cost-effectiveness of early versus late initiation of anti-TNF therapy for the management of CD. Methods: A Markov model was constructed to simulate the progression of a hypothetical cohort of patients with CD after the initiation of either infliximab or adalimumab. Using this model, we compared the lifetime cost-effectiveness of early (≤2 years after diagnosis) versus late (>2 years after diagnosis) initiation of anti-TNF therapy using published loss of response rates. Transition probabilities were determined through a literature search, giving priority to randomized controlled trials with large sample sizes, followed by observational studies if needed. Health state costs were obtained from the Alberta Ministry of Health by linking inpatient, ambulatory, and physician claim databases. Utility scores were obtained from published literature using the Standard Gamble Approach. Deterministic and probabilistic sensitivity analysis was used to characterize uncertainty related to input parameters. Costs and outcomes were discounted at a rate of 5% per year. Results: Over a patient's lifetime, early initiation of infliximab yielded an additional 1.02 quality-adjusted life years (QALYs) and saved $18,054 compared to late initiation of infliximab. Early initiation of adalimumab yielded an additional 0.74 QALYs and saved $18,526 compared to late initiation of adalimumab. At a willingness-to-pay threshold of $50,000 per QALY, early initiation of both infliximab and adalimumab had a 68% chance of being cost-effective, while late initiation had a 32% chance of being cost-effective. Conclusions: Based on our current model, early initiation of either infliximab or adalimumab is cost-saving and dominates late initiation for patients with CD. Sensitivity analysis revealed these results were robust. The results of this study may serve to support early treatment with anti-TNF therapy from both a cost and patient outcome perspective.
Background: The final top-line results of the long-term safety of ADA assessed in patients (pts) with moderately and severely active Crohn's disease (CD) treated in routine clinical practice and enrolled in the global postmarketing observational registry PYRAMID are presented. The primary objective was to rule out a doubled risk of lymphoma for pts treated with ADA compared with the expected background lymphoma rate. Methods: Pts who were newly prescribed ADA or currently receiving ADA according to the local product label were enrolled in the registry and followed for up to 6 years. Adverse events (AEs), serious AEs (SAEs), AEs of special interest, and AEs leading to drug discontinuation were collected. Registry treatment-emergent AEs (TEAE; any event with onset on/after first dose of ADA until 70 days after last ADA injection) and observational AEs (any event occurring from first dose of ADA until last contact) were collected. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 and reported as events/100 patient-years (PY). Results: A total of 5025 pts were evaluated in this analysis (57.1% female, mean age 37.8 yrs at enrollment), representing 16680.4 PYs of ADA exposure over 6 yrs. The mean (SD) duration of ADA exposure during the registry was 1212.4 (835.4) days. A total of 2852 pts (56.8%) had prior biologic use, 1798 (35.8%) used immunomodulators (IMM), and 1463 (29.1%) used corticosteroids (CS) at registry baseline (BL). Overall, 3478 (69.2%) pts discontinued ADA or the registry. A total of 1853 pts (36.9%) reported 4129 treatmentemergent SAEs (24.8/100 PY) (Table). A total of 556 pts reported 792 treatment-emergent serious infections (SI) (4.7/100 PY). The only treatment-emergent SI reported by ≥1% of pts was perianal abscess (0.7/100 PY). The SI rate was higher for pts with concomitant medication at BL (ADA+CS, ADA+IMM, ADA+CS+IMM) vs ADA monotherapy (6.4, 4.8, 5.0 vs 4.2/100PY, respectively). A total of 116 pts experienced 134 treatment-emergent malignancy events (0.8/100 PY), of which 10 were lymphomas. No non-treatment-emergent lymphoma events were reported. The registry exposure-adjusted rate of lymphoma was 0.060/100 PY. The upper bound of the 1-sided 95% CI of this rate was 0.102/100 PYs and fell below 0.168/100 PYs (double the expected rate of 0.084/100 PYs). TEAEs leading to death were reported in 43 pts (0.3/100 PY). Conclusions: The registry achieved the goal of ruling out a doubling of lymphoma risk in pts with CD treated with ADA. No new safety signals were identified.
617 DEFINING PATIENT-CENTERED OUTCOMES FOR IBD AND AN INTERNATIONAL, CROSS-DISCIPLINARY CONSENSUS Andrew H. Kim, Charlotte Roberts, Brian G. Feagan, Rupa Banerjee, Willem Bemelman, Keith Bodger, Marc Derieppe, Axel Dignass, Richard Driscoll, Ray Fitzpatrick, Peter D. Higgins, Paulo G. Kotze, Jillian Meissner, Marian O'Connor, Zhihua Ran, Corey A. Siegel, Helen Terry, Welmoed K. van Deen, Christien Janneke Van Der Woude, Alandra Weaver, Suk-Kyun Yang, Bruce E. Sands, Severine Vermeire, Simon P. Travis Background & Aims Value-based healthcare aims to achieve the best possible health outcomes for the lowest cost. Key to its success involves measuring outcomes that matter most to patients. Currently for inflammatory bowel disease (IBD), registries and clinical trials lack a unifying set of well-defined outcomes, making comparisons between populations difficult. Our goal was to develop a minimum Standard Set of patient-centered outcomes for IBD to provide a common language for outcomes that can be tracked systematically in a variety of healthcare settings. Methods An international, multidisciplinary working group (n=25) from 12 countries within Europe, North America, Asia, Australia, and South America representing patients, gastroenterologists, surgeons, specialist nurses, IBD registries, patientreported outcome measure (PROM) methodologists, and patient organisations participated in a series of teleconferences incorporating a modified Delphi process. Systematic review of existing literature, registry data, patient focus groups and open review periods were used to reach consensus on a minimum set of standard outcome measures, the best validated tools for measurement and baseline risk-adjustment variables. Results A minimum Standard Set of outcomes (Figure/Table 1), preferred tools and measurement frequency was defined by the Working Group for patients (aged >16) with IBD. Outcome domains included patient reported outcomes (including quality of life, symptom score, nutritional status and impact of fistulae); survival and disease control (survival, disease activity/remission, colorectal cancer, and anemia); disutility of care (treatment-related complications); and healthcare utilization (IBD-related admissions and emergency room visits), all measured at baseline and 6 or 12 month intervals. A single, accessible PROM (IBD-Control questionnaire) was recommended. A core set of patients' baseline characteristics including demographics, baseline clinical and
Model structure diagram representing the progression of a hypothetical cohort of patients with moderate to severe Crohn's disease after initiating either early or late anti-TNF therapy.
S-137
AGA Abstracts
AGA Abstracts
615