Benefit of biologics initiation in moderate versus severe rheumatoid arthritis: evidence from a United States registry.

Objectives: To compare clinical outcomes and treatment patterns among patients with moderate vs severe RA following biologic DMARD initiation. Methods: Biologics-naive patients with moderate to severe RA [Clinical Disease Activity Index (CDAI) >10] who initiated a biologic DMARD were selected from the Corrona registry (2001-13). CDAI, functional status [modified HAQ (mHAQ)] and patterns of drug use were compared at 1 and 2 years post-initiation between patients with moderate (CDAI >10⩽22) vs severe (CDAI >22) baseline disease activity. Results: A total of 1596 patients (817 severe, 779 moderate) had ⩾1 year of follow-up and 1269 (635 severe, 634 moderate) had ⩾2 years of follow-up. Patients with severe vs moderate baseline disease activity experienced greater improvements in disease activity [mean change in CDAI -18.9 vs -6.0 at year 1; -21.0 vs -7.1 at year 2 ( P < 0.0001)] and physical function [mean change in mHAQ -0.2 vs -0.1 ( P < 0.0001) at year 1; -0.2 vs -0.1 ( P = 0.0013) at year 2]. Greater proportions of patients with moderate vs severe disease activity achieved remission (CDAI ⩽2.8) [22.7 vs 15.8% ( P = 0.0003) at year 1; 25.9 vs 20.9% ( P = 0.0396) at year 2] or low disease activity (CDAI <10) [60.1 vs 41.2% at year 1; 66.7 vs 49.4% at year 2 ( P < 0.0001)]. Most patients remained on the original biologic drug (>70% at year 1; >62% at year 2). Conclusion: With biologic therapy, RA patients with higher baseline disease activity achieved greater improvements in measures of disease activity than those with lower levels of disease, but less often achieved the common targets of remission or low disease activity.

Benefit-risk trade-offs for treatment decisions in moderate-to-severe rheumatoid arthritis: focus on the patient perspective.

Given the increasing number of available treatments for rheumatoid arthritis (RA) with varying efficacy and safety profiles, it is critical to understand the level of trade-offs that patients are willing to make between benefits and risks. Adult patients with moderate to severe RA were invited to participate in a discrete choice experiment that solicited their preferences for hypothetical RA treatments. Each participant was presented with 14 choice cards asking about their preference between two hypothetical RA treatments with varying levels of efficacy, adverse events, and process-related attributes. A multivariable logistic regression model assessed the association between the attributes and the patient's decision and risk-increases were calculated. 510 eligible patients with moderate to severe RA completed the study. The average age of the participants was 56.4 years, 64.7% were female, and 45.1% received biologic agents. To achieve a 50% improvement in physical function, patients were willing to accept risk-increases of 91.1, 4.7, and 18.4% for abnormal laboratory results, cancer, and serious infection, respectively. Similarly, to achieve a 50% reduction in RA-related pain, patients were willing to accept risk-increases of 70.6, 3.7, and 14.2% for each AE. Moreover, patients were willing to trade risk-increases of 42.0, 2.2, and 8.5% for each AE to obtain a 50% reduction in the number of swollen joints. Patients with moderate to severe RA are willing to accept increased treatment risks to achieve improved physical function and disease control. These attributes are helpful to clinicians to make informed treatment choices.

Treatment Pathways in Patients With Crohn's Disease and Ulcerative Colitis: Understanding the Road to Advanced Therapy.

Background: Patients with Crohn's disease (CD) or ulcerative colitis (UC) often cycle through conventional therapies (CT) with different mechanisms of action (MOA) before initiating advanced therapy (AT). We describe treatment patterns among patients with CD/UC. Methods: Using Merative MarketScan Research databases, adult patients with CD/UC were identified from medical/pharmacy claims (2017-2021). Patients had ≥1 hospitalization or ≥2 outpatient visits (≥30 days apart within 1 year) for CD/UC. Two cohorts were established; cohort 1: Newly diagnosed patients (index date is the date of first diagnosis) and cohort 2: Patients initiating AT (index date is the date of first AT). First-line treatment patterns (cohort 1) and CT pathways before AT initiation (cohort 2) by the number of episodes (ie, adding a new therapy, switching to another therapy, or restarting the same therapy after ≥60 days) and MOA are reported. Results: Among newly diagnosed patients in cohort 1 (CD: n = 1739; UC: n = 2740), 14.4% (CD) and 5.9% (UC) of patients had any AT use during the follow-up period (mean: 2.3 years; ≥ 77% initiated corticosteroids). Among patients in cohort 2 (CD: n = 2594; UC: n = 2431), the mean number of CT episodes before AT initiation was 4.0 ±â€…4.3 (CD) and 5.9 ±â€…5.0 (UC). Among those with ≥1 corticosteroid episode (CD: 82.2%; UC: 91.5%), the mean number of episodes was 4.6 ±â€…4.3 (CD) and 6.3 ±â€…5.0 (UC). Overall, 13.3% (CD) and 23.7% (UC) of patients cycled through 3 MOAs before AT initiation. Conclusions: Despite treatment recommendations, few newly diagnosed CD/UC patients initiated AT as their first treatment. Moreover, patients cycled through multiple CTs before initiating AT.

Mucosal and Transmural Healing and Long-term Outcomes in Crohn's Disease.

BACKGROUND: Healing in Crohn's disease is complex and difficult to measure due to incongruencies between clinical symptoms and disease states. Mucosal healing (MH) and transmural healing (TH) are increasingly used to measure clinical improvement in Crohn's disease, but definitions of MH and TH can vary across studies, and their relationship to long-term outcomes is not clear. To address this knowledge gap, we performed a systematic literature review (SLR) to examine studies measuring MH and TH in Crohn's disease. METHODS: Database records from 2012 to 2022 were searched for real-world evidence and interventional studies that reported the association of MH or TH with clinical, economic, or quality of life outcomes of adult patients with Crohn's disease. RESULTS: A total of 46 studies were identified in the systematic literature review, representing a combined patient population of 5530. Outcomes of patients with MH were reported by 39 studies; of these, 14 used validated scales for endoscopic assessment. Thirteen studies reported outcomes of patients with TH. Among studies that examined the outcomes of patients with and without MH or TH, patients with healing generally experienced improved clinical outcomes and reduced healthcare resource utilization, including fewer hospitalizations and surgeries and improved rates of clinical remission. This was especially true for patients with TH. CONCLUSIONS: Mucosal and transmural healing are associated with positive long-term outcomes for adult patients with Crohn's disease. The adoption of standardized measures and less invasive assessment tools will maximize the benefits of patient monitoring.

Inflammation of the bowel wall is a key component of Crohn's disease (CD). A systematic literature review (SLR) showed bowel wall healing was associated with positive long-term outcomes in CD, supporting healing as an indicator of disease control.

Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials.

BACKGROUND: Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD. METHODS: Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm. RESULTS: Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively. CONCLUSIONS: Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.

Economic Burden of Fatigue in Inflammatory Bowel Disease.

Background: This retrospective study gathered medical/pharmacy claims data on patients with inflammatory bowel disease (IBD) between January 01, 2000 and March 31, 2019 from the IBM MarketScan commercial claims database to assess the real-world impact of fatigue on healthcare costs in patients newly diagnosed with IBD. Methods: Eligible participants were ≥18 years, newly diagnosed with IBD (≥2 separate claims), and had ≥12 months of continuous database enrollment before and after fatigue diagnosis. The date of fatigue diagnosis was the index date; participants were followed for 12 months post-index. Patients with (cases) or without (controls) fatigue were matched 1:1 by propensity score matching. Patients with evidence of prior IBD diagnosis/treatment, or those with a chronic disease other than IBD wherein fatigue is the primary symptom, were excluded. Healthcare resource utilization (HCRU), including hospitalizations, inpatient and outpatient visits, and associated costs were compared between cases and controls. Results: Matched IBD cohorts (21 321 cases/21 321 controls) were identified (42% Crohn's disease [CD] and 58% ulcerative colitis [UC]) with similar baseline characteristics (average age: 46 years; 60% female). Cases versus controls had significantly more all-cause outpatient visits (incidence rate ratio [IRR], 95% confidence intervals [95% CI]: 1.64 [1.61, 1.67], P < .001) and all-cause hospitalizations (IRR [95% CI]: 1.92 [1.81, 2.04], P < .001); as well as significantly higher all-cause total direct healthcare costs (mean: $24 620 vs. $15 324; P < .001). Similar findings were observed for IBD-related outcomes, as well as in CD- and UC-specific subgroups. Conclusions: Presence of fatigue is associated with an increase in HCRU and total medical costs among patients newly diagnosed with IBD.

Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease.

INTRODUCTION: Risankizumab (RZB) and ustekinumab (UST), interleukin (IL)-23 and IL-12/23 inhibitors, respectively, are approved treatments for moderately to severely active Crohn's disease (CD); direct comparison between the two is ongoing. We indirectly compared efficacy of RZB versus UST using data from phase 3 trials (RZB: NCT03104413; NCT03105128; NCT03105102; UST: NCT01369329; NCT01369342; NCT01369355). METHODS: Matching-adjusted indirect comparison was conducted using individual patient-level data from RZB trials and published aggregated data from UST trials. During induction, patients received RZB 600 mg intravenous (IV) at weeks 0, 4, and 8 or a single dose of UST 6 mg/kg IV at week 0. During maintenance, patients received RZB 180 or 360 mg subcutaneous (SC) or UST 90 mg SC every 8 or 12 weeks to 52 weeks. Outcomes included proportion of patients achieving Crohn's Disease Activity Index (CDAI) response (decrease of ≥ 100 points or total score < 150) or remission (CDAI ≤ 150) and endoscopic improvement (measured by the Simple Endoscopic Score in CD [SES-CD]; response, ≥ 50% reduction from baseline; remission, SES-CD ≤ 2) following induction/baseline. RESULTS: Higher proportions of patients achieved clinical and endoscopic outcomes with RZB vs. UST induction treatment, resulting in significantly (p ≤ 0.05) greater percent differences (95% confidence intervals) between groups for CDAI remission (15% [5%, 25%]) and endoscopic response (26% [13%, 40%]) and remission (9% [0%, 19%]). Following maintenance, rates of CDAI remission were similar (range - 0.3% to - 5.0%) for RZB vs. UST. Differences for endoscopic response and remission ranged from 9.3% to 27.7% and 11.6% to 12.5%, respectively; differences were significant (p < 0.05) for endoscopic response for both doses of RZB compared to UST 12-week dosing. CONCLUSIONS: This indirect comparison demonstrated higher rates of clinical and endoscopic outcomes during induction for RZB compared to UST; CDAI remission following maintenance was comparable. Direct comparisons of RZB and UST are warranted to validate these findings.

Using individual patient-level data from risankizumab and aggregated data from ustekinumab phase 3 Crohn's disease trials, we indirectly compared efficacy of risankizumab and ustekinumab to determine whether rates of improvement in disease symptoms (clinical) and endoscopic outcomes differed between treatments. Findings showed that clinical and endoscopic outcomes were more frequently achieved for patients receiving risankizumab versus ustekinumab after induction, while most maintenance outcomes were comparable.

Risankizumab Induction Therapy Achieves Early Symptom Improvements That Are Associated With Future Clinical and Endoscopic Outcomes in Crohn's Disease: Post Hoc Analysis of the ADVANCE, MOTIVATE, and FORTIFY Phase 3 Studies.

BACKGROUND AND AIMS: Crohn's disease (CD) symptoms are a main driver for impaired quality of life and fast relief is important for patient care. Stool frequency (SF) and abdominal pain score (APS) are patient reported outcomes (PROs) measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab (RZB), a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints. METHODS: Individual and combined measures of SF and AP at weeks 1, 2, and 3 were assessed in patients with moderate to severe CD who received 600 mg intravenous RZB or placebo (PBO) in the ADVANCE or MOTIVATE induction studies. Multivariate logistic regression was used to examine the predictiveness of early symptom improvement for clinical and endoscopic outcomes following RZB induction and maintenance. RESULTS: Higher rates of SF/APS clinical remission and enhanced clinical response were observed as early as week 1 with RZB versus PBO. A larger proportion of patients achieved clinical endpoints with RZB versus PBO, irrespective of prior bio-failure status. Early PRO improvement was associated with a greater likelihood of achieving clinical and endoscopic improvement following 12-weeks induction and 52-weeks maintenance RZB dosing. CONCLUSIONS: After the first intravenous RZB induction dose, significantly greater rates of symptom improvement versus PBO were achieved. Improvements could be observed as early as week 1 and were predictive of week 12 and 52 clinical and endoscopic improvement.

Effect of risankizumab on health-related quality of life in patients with Crohn's disease: results from phase 3 MOTIVATE, ADVANCE and FORTIFY clinical trials.

BACKGROUND: Crohn's disease has a substantial negative impact on health-related quality of life (HRQoL). AIM: To examine the effects of risankizumab on HRQoL in Crohn's disease METHODS: We analysed data from patients with Crohn's disease from 12-week induction trials ADVANCE (N = 850) and MOTIVATE (N = 569) with risankizumab 600 mg or 1200 mg intravenous (IV) versus placebo IV and a 52-week maintenance trial FORTIFY (N = 462) with risankizumab 180 or 360 mg subcutaneous (SC) versus placebo SC. Outcomes included Inflammatory Bowel Disease Questionnaire (IBDQ), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), 36-item Short Form Health Survey (SF-36), EuroQol 5-Dimension-5-Level (EQ-5D-5L) and work productivity. The mean change and percentages of patients achieving clinically meaningful improvement in all outcomes were determined at weeks 12 and 52. RESULTS: At week 12, more patients in the risankizumab 600 or 1200 mg groups achieved IBDQ response than with placebo (ADVANCE: 70.2%, 75.5% vs. 47.8%, p ≤ 0.001; MOTIVATE: 61.7%, 68.5% vs. 48.2%, p ≤ 0.01) and FACIT-F response (ADVANCE: 51.3%, 48.0% vs. 35.7%, p ≤ 0.01; MOTIVATE: 44.2%, 49.1% vs. 33.7%, p < 0.05). These improvements persisted at week 52 with risankizumab maintenance treatment. Similar trends were observed for SF-36 physical and mental component summary scores, EQ-5D-5L and activity impairment within work productivity measures. CONCLUSIONS: Risankizumab induction therapy (600 or 1200 mg IV) led to clinically meaningful improvements in disease-specific and general patient-reported outcomes, including fatigue, in patients with moderate to severe Crohn's disease. These improvements were sustained after 52 weeks of risankizumab (180 or 360 mg SC) maintenance therapy.

Efficacy, Safety, Patient Experience, and Tolerability of Risankizumab Administered by On-Body Injector for Moderate to Severe Crohn's Disease.

INTRODUCTION: In patients with moderate to severe Crohn's disease (CD), intravenous induction and subcutaneous maintenance dosing with risankizumab was efficacious and well tolerated. Long-term management of CD via self-administration of risankizumab using an on-body injector (OBI) may improve treatment adherence through convenience and ease of use. METHODS: Within the FORTIFY maintenance study, 46 patients from the United States (US) sites participated in an open-label extension Substudy and received 180 mg or 360 mg risankizumab delivered subcutaneously via OBI [360 mg (2.4 mL, 150 mg/mL) or 180 mg (1.2 mL, 150 mg/mL)]. At the Week 0 visit, patients were trained (pre-injection) by site staff, using Instructions for Use (IFU) and a training video, to self-administer risankizumab at Weeks 0 (on site), 8 (at home), and 16 (on site). Key objectives of the Substudy 4 were to assess OBI usability (observer rating of successful self-administration), hazard-free self-injection at Weeks 0 and 16, and patient rating of acceptability using the Self-Injection Assessment Questionnaire (SIAQ) at Weeks 0, 8, and 16. Additionally, the proportion of patients in clinical remission (CD Activity Index < 150) was collected at Weeks 0 and 16. RESULTS: All patients successfully self-administered risankizumab via OBI, including two patients who successfully self-administered with a second OBI (i.e., required two injection attempts). Acceptability of self-injection was high. Two patients (n = 2) experienced a use-related hazard. Stable clinical remission was observed with both risankizumab doses. Two patients experienced injection site reactions; neither was related to the OBI per investigator's assessment. Two device-related adverse events related to topical adhesive reactions were reported, both mild and resolved. No new safety risks were observed. CONCLUSION: The efficacy and safety of maintenance risankizumab delivered via OBI and OBI usability support the use of this device in patients with moderate to severe CD. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03105102 (FORTIFY).

Adalimumab Is Associated With Lower Healthcare Resource and Steroid Use Versus Vedolizumab in Biologic-Naive Crohn's Disease: A Retrospective Claims Database Analysis.

Background: We compared real-world healthcare resource utilization (HRU), Crohn's disease (CD)-related complications, and time to systemic corticosteroid discontinuation between patients with CD treated with adalimumab versus vedolizumab as initial biologic. Methods: Biologic-naïve adults with CD and ≥2 claims between 05/20/2014 and 09/30/2019 for adalimumab or vedolizumab were identified in the IBM MarketScan research database. Patient characteristics were assessed during the 6-month baseline period before biologic initiation (index date). Adalimumab- and vedolizumab-treated patients were propensity score-matched 1:1 on demographics, disease characteristics, and comorbidities with ≥10% prevalence that differed significantly between groups. Categorical, continuous, and time-to-event outcomes between groups during the 12-month follow-up on/after index were compared with chi-square tests, Wilcoxon rank-sum tests, and Kaplan-Meier analyses, respectively. Results: Adalimumab- and vedolizumab-treated patients were matched (n = 461 per group) and baseline characteristics balanced. Significantly fewer adalimumab- versus vedolizumab-treated patients had a CD-related emergency room visit (12-month proportion: 14.5% vs 21.0%; log-rank P < 0.01) or inpatient admission (14.9% vs 20.2%; log-rank P < 0.05). Rates of CD-related surgeries were similar (9.3% vs 11.5%; log-rank P = 0.282). Among patients without internal/perianal abscess or fistula or intestinal stricture at baseline (N ADA = 360, N VDZ = 364), numerically but not significantly fewer adalimumab- versus vedolizumab-treated patients had CD-related complications at 12 months (18.3% vs 22.3%; P = 0.171). Among patients with corticosteroid use at index (N ADA = 143, N VDZ = 139), significantly more adalimumab- versus vedolizumab-treated patients discontinued corticosteroids (12-month proportion: 90.2% vs 76.3%; log-rank P < 0.001). Conclusions: Patients with CD treated with adalimumab as their first biologic experienced significantly lower CD-related HRU and were more likely to discontinue corticosteroids compared to vedolizumab-treated patients.

The Impact of Intestinal Complications on Health Care Costs Among Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Therapies.

BACKGROUND: Although there is evidence that anti-tumor necrosis factor (TNF) utilization earlier in the inflammatory bowel disease (IBD) course and before the onset of disease-related complications leads to improved patient outcomes, the health care costs and utilization impact have not been well defined. This study assessed differences in health care utilization and costs among patients with IBD treated with anti-TNFs. METHODS: Patients with a diagnosis of ulcerative colitis (UC) or Crohn disease (CD) between January 1, 2001, and December 31, 2014, were identified from a claims database. Patients were required to have ≥1 claim for a 5-aminosalicylic acid, corticosteroid, or immunomodulator after the IBD diagnosis and ≥1 anti-TNF drug claim after the first IBD treatment. Complication and noncomplication cohorts were identified based on disease-related complications and IBD-related hospitalizations or emergency department visits for 6 months before anti-TNF initiation. Generalized linear models were used to compare health care costs and utilization for the 12 months after anti-TNF initiation (follow-up). RESULTS: The study included 6329 patients with CD and 4451 patients with UC. In patients with CD with complications, >33.7% had intestinal strictures and 6% had enteroenteric fistula before anti-TNF treatment. Patients with CD with complications incurred significantly higher IBD-related and all-cause health care costs during follow-up, and patients with UC experienced the same trends. CONCLUSIONS: These results suggest that anti-TNF treatment after, rather than before, a patient develops complications leads to a higher economic burden. However, these findings could also result from patients with more severe disease having early complications that are more difficult to treat.

Dose Escalation Assessment Among Targeted Immunomodulators in the Management of Inflammatory Bowel Disease.

BACKGROUND: The need for individualized treatment regimens is becoming more important in the management of patients with inflammatory bowel disease (IBD). Gastroenterologists may dose adjust either by increasing the dose or shortening the dosing interval from the initial recommended maintenance dose to achieve an appropriate clinical response. Understanding the role of dose escalation in the treatment of IBD in clinical practice provides payers in the United States insight into the real-world cost-effectiveness of targeted immunomodulators (TIMs) in the management of IBD. OBJECTIVE: To assess the prevalence and magnitude of dose escalation for approved IBD therapies. METHODS: Using the Source Healthcare Analytics database, patients with IBD who initiated treatment with a drug of interest from July 2015 to June 2017 were identified. Patient utilization of the TIMs was tracked for 12 months following initiation. All included patients had at least 2 diagnoses for ulcerative colitis or Crohn disease before TIM initiation and at least 5 claims for a drug of interest within the 12 months following initiation. Dose escalation was defined as an increase of at least 30% in the average daily dose (ADD) relative to the patient's expected maintenance dose on 2 consecutive prescriptions. The proportion of patients with dose escalation in the first 12 months after treatment initiation was determined. The magnitude of dose escalation was determined by calculating the patient's ADD across all noninduction dose claims and comparing it with the expected daily dose. Dose escalation prevalence and magnitude were used to quantify the equivalent patient treatment rate representing the number of patients per 100 that could have been treated with standard dosing, given the prevalence of dose escalation in the treated population. RESULTS: 7,028 patients (2,406 infliximab, 1,966 adalimumab, 1,745 vedolizumab, 472 ustekinumab, 285 certolizumab pegol, and 154 golimumab) met eligibility criteria and were included in the study. Among IBD therapies, dose escalation occurred most frequently with infliximab (39%), followed by adalimumab (28%), vedolizumab (23%), ustekinumab (22%), certolizumab pegol (20%), and golimumab (14%). The magnitude of dose escalation was greatest for ustekinumab (131%), followed by infliximab (70%), vedolizumab (62%), adalimumab (59%), certolizumab pegol (50%), and golimumab (45%). The calculated patient equivalence was highest for infliximab (128) and ustekinumab (128) compared with adalimumab (116), vedolizumab (114), certolizumab pegol (110), and golimumab (106). CONCLUSIONS: Among patients with IBD, dose escalation occurred with all TIMs examined with varying degrees of prevalence and magnitude. Real-world utilization patterns of TIMs indicate that dose escalation is an important part of the clinical management of IBD and needs to be considered when evaluating the cost-effectiveness of IBD treatments. DISCLOSURES: Financial support for this study was provided by AbbVie, which participated in study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Ehrenberg and McDonald are employees of IQVIA, which received funding from AbbVie to participate in this research. Griffith and Theigs are employed by AbbVie and may own stock or stock options in AbbVie.

Assessing disease severity in bio-naïve patients with RA on treatment with csDMARDs: insights from the Corrona Registry.

INTRODUCTION: This study aimed to characterize disease burden among patients with rheumatoid arthritis (RA) with moderate-to-high disease activity who had received conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy for ≥ 6 months but had not advanced to a biologic therapy. METHODS: Patients enrolled in the US Corrona RA Registry between June 1, 2014, and January 30, 2018, with 6 months of continuous csDMARD monotherapy, with moderate-to-high disease activity, who remained biologic naive, and who had ≥ 1 follow-up visit were identified. Disease activity was assessed among patients with a 6-month follow-up visit (± 3 months). Descriptive statistics were used to compare demographics and disease characteristics between patients with or without treatment advancement. RESULTS: The study included 409 patients with a disease activity assessment at 6 months (mean (SD) age 65.9 (12.6) years; mean duration of csDMARD therapy 407 (221) days). Of those patients, more than half (54%, n = 219) remained in moderate-to-high disease activity. Patients remaining in moderate-to-high vs. remission-to-low disease activity had higher baseline swollen (6.1) and tender joint counts (6.8). Over the 6-month period, treatment advancement occurred in 29% of patients. Those who advanced treatment (n = 118) vs. did not advance treatment (n = 291) were younger, had a shorter duration of RA, had higher disease activity, and reported higher levels of pain and fatigue. CONCLUSIONS: The substantial number of patients with persistent moderate-to-high disease on csDMARDs over a 6-month period and who did not advance treatment indicates that there is considerable need for a treat-to-target approach to care for patients with RA.Key Points•For patients with RA and an inadequate response to treatment with initial csDMARD monotherapy, guidelines recommend treatment advancement; however, this may not be occurring in real-world clinical settings.•In the current study, a substantial proportion of patients (54%) on csDMARDs had persistent moderate-to-severe disease activity at the 6-month (± 3 months) follow-up visit; however, only 29% of patients had their medication treatment advanced, indicating that there is considerable need for a treat-to-target approach to care for patients with RA.•Patients with younger age, shorter RA duration, and higher disease activity were more likely to have their medication treatment advanced, which suggests that potentially more aggressive treatment of disease activity is needed across the whole RA population.

Retrospective Analysis of the Impact of Adalimumab Initiation on Corticosteroid Utilization and Medical Costs Among Biologic-Naïve Patients with Rheumatoid Arthritis.

INTRODUCTION: Treatment guidelines recommend low-dose corticosteroids as short-term therapy among rheumatoid arthritis (RA) patients. However, it may be difficult to wean/eliminate steroids once initiated. Initiation of more effective therapies such as biologics may help to taper corticosteroid use. The objective was to examine the impact of adalimumab (ADA) initiation on steroid utilization and non-drug medical costs among patients with RA. METHODS: A retrospective analysis was conducted among adult RA patients initiating ADA as the initial biologic in the MarketScan Database (2012-2016). Study outcomes included whether oral/injectable steroids were used, daily dose, dosage categories (< 5 and ≥ 5 mg/day), number of steroid injections, and non-drug medical costs. Outcomes were compared 6 months pre- and post-ADA initiation. Mixed effects logistic, classical linear, multinomial logistic models, and linear model with a log link and gamma distribution were used to adjust for patient demographic and health characteristics. RESULTS: The sample included 7404 ADA initiators. Compared to pre-ADA initiation, in the post-initiation period there was a reduction in proportions of patients using oral steroids (from 71.80 to 62.56%) and injectable steroids (from 34.91 to 29.88%), average daily dose of oral steroids (from 3.30 to 2.62 mg/day), patients with dose ≥ 5 mg/day (from 21.76 to 16.34%), number of injections (from 0.64 to 0.53), and non-drug medical costs (from $5356.30 to $5146.84) (P < 0.01). The multivariate analysis produced similar patterns. For example, post-ADA initiation, patients were less likely to use oral steroids [odds ratio (OR) 0.51; 95% confidence interval (CI) 0.47-0.56]; coefficient estimate for daily dose reduction was - 0.68 (95% CI - 0.81 to - 0.56); ratio estimate for medical costs was 0.91 (95% CI 0.86-0.97). CONCLUSIONS: Among patients with RA, following ADA initiation, there is a reduction in steroid utilization and dosage, and non-drug medical costs. Prospective studies should be conducted to confirm this relationship in the future.

Economic Outcomes of Inflammatory Bowel Disease Patients Switching to a Second Anti-Tumor Necrosis Factor or Vedolizumab.

Background: Anti-tumor necrosis factor (TNF) therapies have been the mainstay of inflammatory bowel disease (IBD) treatment for nearly 2 decades. Therapies with novel mechanisms of action have been recently developed. This study compared healthcare resource utilization (HRU) and costs incurred while switching from an initial anti-TNF to another anti-TNF versus switching to vedolizumab. Methods: Adults with IBD who switched from initial anti-TNF to another anti-TNF or vedolizumab were identified from Truven MarketScan claims database (January 1, 2000-September 30, 2017). Patient characteristics were assessed during the 6-month period before the initiation date of the switched-to treatment (index date). Adjusted analyses of all-cause and disease-related HRU and costs during the 6-month period after the index date (study period) were performed. Anti-TNF and vedolizumab switchers with Crohn's disease (CD) and ulcerative colitis (UC) were separately compared. Results: A total of 502 vedolizumab, 1708 adalimumab, 755 infliximab, and 703 other switchers with CD and 461, 428, 311, and 148 with UC, respectively, were identified. Patient demographics were similar across cohorts. Total all-cause costs were significantly higher for vedolizumab than adalimumab, infliximab, and certolizumab switchers in the CD cohort and adalimumab and infliximab in the UC cohort. In both cohorts, adalimumab and other switchers had fewer all-cause and IBD-related outpatient visits than vedolizumab switchers. Conclusions: CD/UC patients who switched to vedolizumab from initial anti-TNF had higher total and treatment costs than patients who switched to another anti-TNF, except for UC patients who switched to golimumab. Prospective studies should be conducted to confirm these findings.

Longterm, Real-world Safety of Adalimumab in Rheumatoid Arthritis: Analysis of a Prospective US-based Registry.

OBJECTIVE: To assess longterm safety in a US cohort of patients with rheumatoid arthritis (RA) treated with adalimumab (ADA) in real-world clinical care settings. METHODS: This observational study analyzed the longterm incidence of safety outcomes among patients with RA initiating ADA, using data from the Corrona RA registry. Patients were adults (≥ 18 yrs) who initiated ADA treatment between January 2008 and June 2017, and who had at least 1 followup visit. RESULTS: In total, 2798 ADA initiators were available for analysis, with a mean age of 54.5 years, 77% female, and mean disease duration of 8.3 years. Nearly half (48%) were biologic-naive, and 9% were using prednisone ≥ 10 mg at ADA initiation. The incidence rates per 100 person-years for serious infections, congestive heart failure requiring hospitalization, malignancy (excluding nonmelanoma skin cancer), and all-cause mortality were 1.86, 0.15, 0.64, and 0.33, respectively. The incidence of serious infections was higher in the first year of therapy (3.44, 95% CI 2.45-4.84) than in subsequent years, while other measured adverse effects did not vary substantially by duration of exposure. The median time to ADA discontinuation was 11 months, while the median time to first serious infection among those experiencing a serious infection event was 12 months. CONCLUSION: Analysis of longterm data from this prospective real-world registry demonstrated a safety profile consistent with previous studies in patients with RA. This analysis did not identify any new safety signals associated with ADA treatment and provides guidance for physicians prescribing ADA for extended periods.

Direct medical costs for patients seeking emergency care for losses of epilepsy control in a U.S. managed care setting.

The objective of this retrospective claims database study was to compare the costs of care from a U.S. payer perspective before and after epilepsy treatment in emergent care settings and, secondarily, to describe the frequency of toxic effects and physical injuries occurring on the date of the emergent care. Nine and four-tenths percent of patients receiving emergent care for epilepsy (114/1213) had an injury or adverse antiepileptic drug effect on the same date. The majority of incidents were superficial injuries and contusions (28%), fractures (21%), open wounds or injury to blood vessels (19%), intracranial injury (10%), and/or medication toxicity (10%). Both non-epilepsy-related (US$12,745.56) and epilepsy-related (US$2013.62) direct medical costs of care pre-index were significantly different from those post-index (US$15,274.95 and US$7087.53, respectively). The cost of care for possible reestablishment of epilepsy control and treatment of co-occurring injuries is significant when compared with that for the period prior to seizure.

Economic Burden of Switching to Different Biologic Therapies Among Tumor Necrosis Factor Inhibitor-Experienced Patients with Psoriatic Arthritis.

INTRODUCTION: Patients with psoriatic arthritis (PsA) who receive an initial tumor necrosis factor inhibitor (TNFi) may switch to another TNFi or a non-TNFi biologic therapy. This study compared the healthcare resource use (HRU), expenditures, and time to discontinuation among TNFi-experienced patients with PsA who switched to different biologic therapies in the United States (US). METHODS: Adults with PsA who discontinued an initial TNFi (adalimumab, etanercept, infliximab, golimumab, or certolizumab pegol) and switched to another TNFi or a non-TNFi (ustekinumab or secukinumab) were identified in the Symphony Health Solutions database [Quarter (Q)1 2010-Q2 2017]. Eligible patients had claims data activity for ≥ 12 months before (baseline) and after (study period) the switching date. All-cause HRU, costs (2017 US dollars), and time to discontinuation during the study period were compared between patients switching to another TNFi vs. a non-TNFi (index drug). Multivariable regression models adjusted for baseline covariates (index year, age, sex, initial TNFi, comorbidities, baseline HRU, and PsA-related treatment history). RESULTS: Of 2107 patients switching to another TNFi and 253 switching to a non-TNFi, adalimumab and etanercept were the most common initial TNFi in both cohorts. During the study period, patients switching to another TNFi had significantly fewer dermatologists visits (0.43; p < 0.01) but more rheumatologist visits (1.56, p < 0.01) than patients switching to a non-TNFi. Patients switching to another TNFi vs. a non-TNFi incurred significantly lower total average healthcare expenditures (adjusted difference: $17,625; p < 0.01), driven by lower prescription drug (adjusted difference: $17,172; p < 0.01) and hospitalization expenditures (adjusted difference: $5772; p = 0.04). Patients who switched to another TNFi vs. a non-TNFi continued on their index therapy significantly longer (median time to discontinuation: 8.31 vs. 5.68 months; log-rank p < 0.01). CONCLUSIONS: Patients with PsA who switched to another TNFi had lower total healthcare expenditures and longer persistence compared with patients who switched to a non-TNFi biologic. FUNDING: AbbVie.

A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARDs Among Patients with Rheumatoid Arthritis in the United States.

INTRODUCTION: Understanding the effects of corticosteroid utilization prior to initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform decision-makers on the appropriate use of these medications. This study examined treatment patterns and associated burden of corticosteroid utilization before initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. METHODS: A retrospective analysis was conducted of adult RA patients in the US MarketScan Database (2011-2015). The following patterns of corticosteroid utilization were analyzed: whether corticosteroids were used; duration of use (short/long duration defined as < or ≥ 3 months); and dosage (low as < 2.5, medium as 2.5 to < 7.5 and high as ≥ 7.5 mg/day). Effects of corticosteroid use on time to biologic DMARD initiation were examined using Cox proportional hazards models. Likelihood and number of adverse events were examined using logistic and negative binomial regression models. Generalized linear models were used to examine healthcare costs. Independent variables in all models included patient demographics and health characteristics. RESULTS: A total of 25,542 patients were included (40.84% used corticosteroids). Lower hazard of biologic DMARD initiation was associated with corticosteroid use (hazard ratio = 0.89, 95% confidence interval = 0.83-0.96), long duration and lower dose. Corticosteroid users compared to non-users had higher incidence rates of various adverse events including cardiovascular events (P < 0.05). Higher likelihood of adverse events was associated with corticosteroid use and long duration of use, as was increased number of adverse events. Corticosteroid users had a greater annualized mean number of physician visits, hospitalizations, and emergency department (ED) visits than non-users in adjusted analysis. Corticosteroid users compared to non-users had higher mean costs for total healthcare, physician visits, hospitalizations, and ED visits. CONCLUSIONS: Among patients with RA, corticosteroid utilization is associated with delayed initiation of biologic DMARDS and higher burden of adverse events and healthcare utilization/costs before the initiation of biologic DMARDs. FUNDING: AbbVie Inc.