Indirect treatment comparison of oral versus injectable azacitidine as maintenance therapy for acute myeloid leukemia.

Aim: Evaluate the relative efficacy of oral versus injectable azacitidine (AZA) maintenance therapy in acute myeloid leukemia (AML) after complete remission. Materials & methods: Systematic literature review identified QUAZAR AML-001, HOVON 97 AML, UK NCRI AML16 and QoLESS-AZA-AMLE (sensitivity analysis) trials. Network meta-analysis and matching-adjusted indirect comparisons assessed survival outcomes. Results: In the network meta-analysis, combining the HOVON 97 and UK NCRI trials, oral AZA (QUAZAR) was associated with significantly improved overall survival (OS) versus injectable AZA (hazard ratio: 0.744; 95% credible interval: 0.557-0.998). After matching-adjusted indirect comparisons, to address differences in patient characteristics across trials, OS improvements were maintained with oral versus injectable AZA (hazard ratio: 0.753; credible interval: 0.563-0.998). Conclusion: In AML, maintenance therapy with oral AZA was associated with improved OS versus injectable AZA.

Older people with acute myeloid leukemia (AML) may have remission with or without blood count recovery, after first-line chemotherapy; however, remission is short lived and overall survival is limited (7­12 months). Ongoing treatment (maintenance therapy) after response to initial chemotherapy may prolong remission. Maintenance therapy with azacitidine (AZA) given by injection beneath the skin (subcutaneous) or into a vein (intravenous) can extend disease-free survival compared with no further treatment and best supportive care. However, treatment with intravenous AZA may only extend overall survival in certain patients. ONUREG^® is a novel formulation of AZA that can be taken by mouth (orally), remains in the body for longer periods and has the potential for significant clinical benefits compared with intravenous AZA. Presently, there are no studies directly comparing outcomes of maintenance therapy with oral and injectable AZA in older people with AML. In this analysis, we used an indirect treatment comparison method including four clinical trials to explore the survival benefit associated with ONUREG and injectable AZA when used as maintenance therapies after response to initial chemotherapy in older people with AML. Findings showed ONUREG significantly improved overall survival compared with injectable AZA, with an almost 26% reduction in the risk of death. These results suggest that maintenance therapy with ONUREG significantly improves overall survival compared with injectable AZA in older people with AML who may have remission with or without blood count recovery, after first-line chemotherapy.

The cost-effectiveness of initial treatment of multiple myeloma in the U.S. with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment.

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99-06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99-06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.

Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis.

Background: Given rapid innovation in advanced therapies for moderately to severely active ulcerative colitis (UC), we investigated their comparative efficacy and safety during induction and maintenance through network meta-analysis. Methods: Using Bayesian methods, endpoints of clinical remission and clinical response per Full Mayo score, and endoscopic improvement were assessed in bio-naive and -exposed populations. Safety was assessed in overall populations by all adverse events (AEs), serious AEs, discontinuation due to AEs, and serious infections. Phase 3 randomized controlled trials were identified via systematic literature review, including the following advanced therapies: infliximab, adalimumab, vedolizumab, golimumab, tofacitinib, ustekinumab, filgotinib, ozanimod, and upadacitinib. Random effects models were used to address between-study heterogeneity. Intent-to-treat (ITT) efficacy rates were calculated by adjusting maintenance outcomes by likelihood of induction response. Results: Out of 48 trials identified, 23 were included. Across all outcomes and regardless of prior biologic exposure, ITT efficacy rates were highest for upadacitinib, owing to its highest ranking for all efficacy outcomes in induction and for all but clinical remission during maintenance among bio-naive induction responders. For all advanced therapies versus placebo, there were no significant differences in serious AEs or serious infections across therapies. For all AEs, golimumab had higher odds versus placebo during maintenance; for discontinuation due to AEs, upadacitinib had lower odds versus placebo during induction, while ustekinumab and vedolizumab had lower odds versus placebo during maintenance. Conclusions: Upadacitinib may be the most efficacious therapy for moderately to severely active UC based on ITT analyses, with similar safety across advanced therapies.

Cost-Effectiveness of Chimeric Antigen Receptor T Cell Therapy in Patients with Relapsed or Refractory Large B Cell Lymphoma: No Impact of Site of Care.

INTRODUCTION: Cost-effectiveness data on chimeric antigen receptor (CAR) T cell therapies for relapsed/refractory large B cell lymphoma (R/R LBCL), accounting for inpatient/outpatient site of care (site), are sparse. METHODS: This payer model compares lifetime costs/benefits for CAR T cell-treated (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisa-cel]) patients with R/R LBCL in the USA. Three-month post-infusion costs were derived from unit costs and real-world all-payer (RW) site-specific utilization data for 1175 patients with diffuse R/R LBCL (CAR T cell therapy October 2017-September 2020). Therapy- and site-specific grade 3+ cytokine release syndrome (CRS) and neurologic event (NE) incidences were imputed from published trials. Lifetime quality-adjusted life-years (QALYs) and long-term costs were calculated from therapy-specific overall and progression-free survival data, adjusted for differences in trial populations. The base case used 17% outpatient site (RW) for all therapies. ZUMA-1 trial cohorts 1/2 informed other axi-cel base case inputs; ZUMA-1 cohorts 4/6 data (updated safety management) supported scenario analyses. RESULTS: Base case total costs for axi-cel exceeded liso-cel ($637 K versus $621 K) and tisa-cel ($631 K versus $577 K) costs. Three-month post-infusion costs were $57 K to $59 K across all therapies. Total QALYs for axi-cel also exceeded those for liso-cel (7.7 versus 5.9) and tisa-cel (7.2 versus 5.0) with incremental costs per QALY gained of $9 K versus liso-cel and $25 K versus tisa-cel. Base case incremental net monetary benefit was $255 K (95% confidence interval (CI) $181-326 K) for axi-cel versus liso-cel, and $280 K (95% CI $200-353 K) versus tisa-cel. Longer survival with axi-cel conferred higher lifetime costs. In all scenarios (e.g., varied outpatient proportions, CRS/NE incidence), axi-cel was cost-effective versus both comparators at a maximum willingness-to-pay of under $26 K/QALY as a result of axi-cel's higher incremental survival gains and quality-of-life. CONCLUSIONS: Axi-cel is a cost-effective CAR T cell therapy for patients with R/R LBCL compared to tisa-cel and liso-cel. Site of care does not impact the cost-effectiveness of CAR T cell therapy.

Treatment of transfusional iron overload in patients with myelodysplastic syndrome or severe anemia: data from multicenter clinical practices.

BACKGROUND: Patients with myelodysplastic syndrome (MDS) or severe anemia requiring repeated red blood cell (RBC) transfusions risk developing transfusional iron overload, which can reduce survival. Iron chelation therapy (ICT) has been shown to improve survival and quality of life in patients; however, ICT utilization in clinical practices is not well understood. STUDY DESIGN AND METHODS: Medical records of patients diagnosed with MDS or severe anemia at least 6 months before data extraction, aged at least 21 years at diagnosis, and who received at least one RBC transfusion were reviewed. ICT eligibility was defined as at least 20 units of RBCs transfused or at least two serum ferritin levels exceeding 1000 microg/L. Study endpoint was ICT treatment rate among ICT-eligible patients with lower-risk MDS (International Prognostic Scoring System [low or intermediate-1]; World Health Organization [refractory anemia {RA}, refractory anemia with ringed sideroblasts {RARS}, refractory cytopenia with multilineage dysplasia {RCMD}, refractory cytopenia with multilineage dysplasia and ringed sideroblasts, or 5q]; French-American-British [RA/RARS]). RESULTS: Among 78 ICT-eligible patients with lower-risk MDS, 32 (41%) received ICT. At ICT initiation, treated patients received on average 13.3 transfusions (27.6 units) and mean first post-ICT initiation serum ferritin was twice the MDS Foundation recommendation at 1949 microg/L. Median overall survival for all ICT-eligible patients was significantly longer for those ICT-treated patients than untreated patients (8.7 years vs. 4.7 years, log-rank p = 0.02; multivariate hazard ratio 0.372, p = 0.03). CONCLUSION: This study finds only 41% of ICT-eligible patients with lower-risk MDS received ICT in clinical practice, and treatment was initiated later than recommended. Receipt of ICT was associated with significantly longer survival.

Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review.

OBJECTIVE: To assess the effectiveness, safety, and treatment patterns of anti-angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS: We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off-label) as first-line anti-angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS: Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS: Currently available anti-angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better-tolerated therapies for mRCC.

Cost utility of adalimumab versus infliximab maintenance therapies in the United States for moderately to severely active Crohn's disease.

OBJECTIVE: To determine and compare the cost utilities of the tumour necrosis factor (TNF) antagonists adalimumab and infliximab as maintenance therapies for patients in the US with moderately to severely active Crohn's disease. METHODS: Maintenance regimens of adalimumab (40 mg every other week) and infliximab (5 mg/kg) were compared using primary data from the CHARM and published data from the ACCENT I clinical trials. Differences in study samples were minimized by matching and weighting baseline characteristics (Crohn's Disease Activity Index score, age and sex) between the patient groups using the primary clinical trial data. Utilization data were estimated from trial data. Unit costs of TNF antagonists (year 2007 values), hospitalizations (year 2006 values), and other medical costs (year 2006 values) were derived from a systematic literature search. Standard gamble-calculated primary data were used to derive health-utility estimates. Data were analysed in a cost-utility framework from a private payer perspective over a 56-week time horizon. Univariate and probabilistic sensitivity analyses were used to explore uncertainty related to the base-case cost-utility analysis. Given the time horizon, costs and effects were not discounted. RESULTS: Adalimumab- and infliximab-treated patients were in remission for 47.2% and 37.1% of the 56-week period, respectively. Hospital admissions were 34-40% lower for adalimumab than for infliximab, based on the model and observed data, respectively. Patients treated with adalimumab accrued greater expected QALYs (0.014; 95% CI 0.000, 0.022) and lower costs (-$US4852; 95% CI -6758, 491) in the first year of therapy than patients treated with infliximab. Compared with infliximab maintenance therapy, adalimumab had lower drug and administration costs, less drug waste, and lower hospitalization rates. Univariate and multivariate probabilistic sensitivity analyses suggested that these results were robust. CONCLUSIONS: This analysis suggests that adalimumab maintenance therapy is a dominant strategy versus infliximab maintenance therapy for patients with moderate to severe Crohn's disease. Adalimumab appeared more effective and less costly than infliximab.

Cost-effectiveness model for a hypothetical monotherapy vs standard of care in adult patients with treatment-resistant depression.

BACKGROUND: Patients with treatment-resistant major depressive disorder (TRD) have limited treatment options. We developed an early stage cost-effectiveness model of TRD to explore the potential value of a hypothetical monotherapy relative to the standard of care (SOC). The relative impacts of the monotherapy's three differentiating features over SOC are explored: efficacy advantage, tolerability advantage, and price premium. METHODS: We adapted an existing economic model of TRD to evaluate the cost-effectiveness of a hypothetical monotherapy for TRD with a 25% efficacy advantage, a 10% tolerability advantage, and a 50% price premium over SOC (selective serotonin reuptake inhibitor plus atypical antipsychotics [SSRI + AAP]). The model is a hybrid of a decision tree that captures patients' outcomes after an 8-week acute treatment phase and a Markov model that simulates patients' depression course through a 10-month maintenance phase. Sensitivity (deterministic and probabilistic) and scenario analyses were conducted to characterize the relative impacts of the monotherapy's three differentiating features over SOC. RESULTS: Over the 12-month time horizon, the hypothetical monotherapy is shown to dominate SOC; it generates lower costs and higher quality-adjusted life years in comparison to SSRI + AAP. Sensitivity and scenario analyses showed that this dominance depends largely on the monotherapy's efficacy and tolerability advantages over SOC. Specifically, a monotherapy with ≥ 12% efficacy or ≥70% tolerability advantage (and a 50% price premium) will always be superior to SSRI + AAP. Between these two extremes, most profiles, nonetheless, generate incremental cost-utility ratios for the monotherapy, which fall below common payer willingness-to-pay thresholds. CONCLUSION: Our adaptation of an existing economic model of TRD provides a flexible platform for researchers to evaluate the efficacy/tolerability improvements required for a successful new TRD product and for decision-makers to assess the cost-effectiveness impact of uncertainties inherent in early stage product development in TRD.

Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA.

AIM: To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain. METHODS: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature. RESULTS: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive. CONCLUSION: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Treatment of peripheral neuropathic pain: a simulation model.

OBJECTIVE: To describe the use of a generalizable stochastic-simulation model of the treatment of neuropathic pain associated with peripheral neuropathies. METHODS: We developed a model to simulate treatment outcomes in a hypothetical cohort of patients with peripheral neuropathies. Each patient was randomly assigned an average pretreatment daily pain score (on a 0-10 scale), based on an assumed distribution of mean pretreatment pain scores in the cohort. Patients were randomly assigned daily pain scores, based on their pretreatment average and an assumed distribution of daily pain scores around this mean. Treatment outcomes were then simulated using the expected mean change (vs. baseline) in pain scores. Model outcomes include the expected increase in days with no or mild pain (score < or = 3), days with > or = 30% and > or = 50% reductions in pain intensity, and days with 2- and 3-point absolute reductions in pain intensity. To illustrate its use, the model was estimated over a 12-week period using data from a recent clinical trial of a new antiepileptic (pregabalin). RESULTS: Treatment over 12 weeks (84 days) was projected to result in 26 (+/-0.4) (mean [+/-SE]) additional (vs. no treatment) days with no or mild pain, 33 (+/-0.5) days with a > or = 30% reduction in pain intensity, 28 (+/-0.4) days with > or = 50% reduction in pain intensity, and 34 (+/-0.5) and 30 (+/-0.5) days with > or = 2-point and > or = 3-point absolute reductions in pain intensity. CONCLUSIONS: When combined with data on health-state utilities and treatment costs, this new analytical tool can provide a foundation for formal cost-effectiveness evaluations of interventions for painful peripheral neuropathies.

Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin + VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin + VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin + VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE. METHODS: A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin + VKA in adult patients treated for acute DVT or PE. All patients entered the model in the 'on-treatment' state upon commencement of oral rivaroxaban or enoxaparin + VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used. RESULTS: Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin + VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model's results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin + VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin + VKA approximately 76% of the time. LIMITATIONS: The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. 'Real-world' applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system. CONCLUSION: Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.

Safety and treatment patterns of angiogenesis inhibitors in patients with metastatic renal cell carcinoma: evidence from US community oncology clinics.

Safety and treatment patterns of sunitinib and sorafenib in metastatic renal cell carcinoma (mRCC) had been previously reported using retrospective chart review of patients treated in US tertiary centers. Because practice patterns may vary between hospital- and office-based settings, this study examined safety and treatment patterns of these agents in US community oncology clinics. Medical records were retrospectively reviewed for 250 patients with mRCC treated at 18 community oncology clinics. Eligible patients were ≥18 years old and received ≥1 prescription for sunitinib (n = 131) or sorafenib (n = 119) as first-line anti-angiogenic treatment. Rates of adverse events (AEs) and treatment modifications were analyzed; reasons for treatment modifications were examined. Median duration of first-line sunitinib and sorafenib treatment was 5.9 and 5.5 months, respectively. Among patients treated with sunitinib and sorafenib, 86% (30%) and 87% (28%), respectively, experienced ≥1 all-grade (grade 3/4) AE. The most common AEs were fatigue/weakness in sunitinib (all-grade: 42%; grade 3/4: 5%) and skin rash in sorafenib (all-grade: 35%; grade 3/4: 6%). Sixty-two and 64% of patients treated with sunitinib and sorafenib, respectively, had ≥1 treatment modification due to AEs. Recorded AE rates in patients with mRCC treated with angiogenesis inhibitors in community practice tended to be lower than in tertiary centers, possibly due to shorter treatment duration. Rates of treatment modifications due to AEs tended to be higher in community practice. This study provides evidence from an office-based setting of unmet need for agents that may provide improved tolerability in mRCC.

Lifetime costs to Medicare of providing care to patients with chronic lymphocytic leukemia.

This study estimated the average lifetime costs of patients with chronic lymphocytic leukemia (CLL) relative to similar patients without cancer. An analysis of the Medicare 5% database (1999-2007) was conducted. Each patient with CLL was matched up to three patients without cancer based on year of birth, gender, race and state. Average total lifetime costs were estimated using the Kaplan-Meier sample average estimator and stratified by treatments. For patients who died, average monthly costs during continuing and terminal phases were compared between cohorts. A total of 7463 patients with CLL and 22 331 matched controls were identified (mean age: 76 years; proportion of women: 49%). The mean observation period was 39.4 months for patients with CLL and 45.9 months for matched controls. Patients with CLL incurred average costs of $87,151 compared to $47 642 for matched controls (p < 0.001). Among common CLL treatments, average costs per patient were $5140 for rituximab and $953 for radiation therapy. Compared to matched controls, patients with CLL had significantly higher monthly costs during the continuing and terminal phases. This study showed that average lifetime costs to Medicare were $87,151 for patients with CLL compared to $47,642 for matched controls without cancer, for a significant difference of $39,509.

Risk-benefit analysis of adalimumab versus traditional non-biologic therapies for patients with Crohn's disease.

BACKGROUND: Adalimumab is indicated for the treatment of moderately to severely active Crohn's disease (CD). A systematic analysis of risks and benefits of adalimumab versus traditional non-biologic therapies for patients refractory to non-biologic therapy is lacking. METHODS: A base-case analysis compared expected benefits of adalimumab therapy with a 12-week stopping rule for non-responders versus non-biologic therapies using data from clinical trials (CHARM, CLASSIC I). Adverse events (AEs) recorded in clinical trials (CHARM, CLASSIC I, CLASSIC II, GAIN, open-label extensions) were compiled. Sensitivity analyses incorporated all observed benefits of adalimumab and placebo (CHARM, CLASSIC I, GAIN) and observed AEs from a systematic literature review of non-biologic therapies (MEDLINE search of randomized trials 1990-2007). Distributional information from maintenance clinical trial observations and benefit model predictions were used in a probabilistic simulation. Incremental net benefits were estimated based on utility estimates from the literature. RESULTS: Average time in remission (i.e., CDAI <150) over 1 year of therapy was 39.9% for adalimumab versus 6.6% for traditional non-biologic therapies. Adalimumab was associated with fewer expected hospitalizations, better fistula closure rates, and lower AE rates. These findings were robust in sensitivity analyses. In the probabilistic simulation, with serious AEs as a composite of risks, adalimumab provided greater benefits with fewer AEs versus non-biologic therapies (P < 0.01). Adalimumab demonstrated greater incremental net quality-adjusted life-years (0.12) versus non-biologic therapies. CONCLUSIONS: Adalimumab demonstrated greater benefits and lower rates of AEs versus traditional non-biologic therapies for patients with moderately to severely active CD who were refractory to non-biologic therapies.