Initial Tumor Necrosis Factor Inhibitor Research Articles

Real-World Treatment and Care Patterns in Patients With Rheumatoid Arthritis Initiating First-Line Tumor Necrosis Factor Inhibitor Therapy in the United States.

Treatment guidelines for rheumatoid arthritis (RA) recommend targeting low disease activity or remission and switching therapies for patients not reaching those targets. We evaluated real-world use of disease activity measures, treatment discontinuation, and switching patterns among patients with RA initiating a first-line tumor necrosis factor inhibitor (TNFi). Data from adult patients with RA initiating a first-line TNFi were collected from the American Rheumatology Network (January 2014-August 2021). The proportion of patients with recorded disease activity scores (Clinical Disease Activity Index [CDAI] or Routine Assessment of Patient Index Data 3 [RAPID3]) at TNFi initiation was assessed. Among patients with moderate or severe RA at TNFi initiation, reasons for discontinuation and subsequent advanced therapy were evaluated. Among TNFi initiators (n=15,182), 44.8% recorded a CDAI/RAPID3 score at treatment initiation; of those who did not, 47.0% had recorded a tender and/or swollen joint count or pain score. Among patients with moderate or severe RA (n=1,651), 52% discontinued their initial TNFi during follow-up, of which 15%, 46%, 28%, and 12% initiated the same TNFi, another TNFi, a non-TNFi biologic, or a Janus kinase inhibitor, respectively. The proportion of patients restarting the same TNFi or initiating another TNFi varied according to TNFi discontinuation reason. In clinical practice, over half of patients with RA initiating a first-line TNFi did not have baseline disease activity assessments. Many patients cycled through TNFi despite citing lack of efficacy as the most common reason for discontinuation. Consistent, objective monitoring of treatment response and timely switch to effective therapy is needed in patients with RA.

Comparison of a second TNFi vs other biologic or targeted synthetic DMARD following an initial TNFi.

BACKGROUND: Patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis may require treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Often, a tumor necrosis factor inhibitor (TNFi) is the initial b/tsDMARD. The TNFi may not be effective or may not be well tolerated, so patients will opt for a different TNFi or switch to a non-TNFi b/tsDMARD. No preference for a TNFi or non-TNFi has been established and guidelines are unclear. OBJECTIVE: To evaluate effectiveness by comparing patients using a second TNFi vs a non-TNFi after initial use of TNFi based on treatment patterns and health care utilization. METHODS: This retrospective analysis used Medicare Advantage prescription drug (MAPD) plan, Medicaid, and commercial plan claims data from Humana's Research Database (Louisville, KY). The first claim for TNFi or non-TNFi (July 1, 2016, to June 30, 2018) following earlier TNFi was the index date. Patients were required to have pre-index enrollment of 6 months and 12 months post-index along with diagnosis of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, or psoriasis. During the 12-month follow-up, persistence to the index TNFi or non-TNFi was measured as continued therapy without a gap exceeding 45 days (81 days for intravenous infusions). Adherence was proportion of days covered at least 0.8. Addition of a nonbiologic DMARD or corticosteroid was also identified. Inpatient admissions and emergency department visits were observed. Inverse probability of treatment weights was used to balance cohorts. Logistic regression models were fit to TNFi vs non-TNFI on treatment and utilization measures. RESULTS: Of identified patients, 1,022 were indexed to a second TNFi and 1,024 were indexed to non-TNFi. Weighted cohorts were balanced, with mean age 56.5 vs 56.4 years, 70.5% vs 70.7% female sex, and 68.0% vs 67.9% MAPD plan. No differences were observed on persistence or adherence, with adjusted odds ratios (OR) of 1.05 (95% CI = 0.91-1.20) and 1.04 (0.91-1.20), respectively. No differences were observed for changes in therapy via switching to another TNFi/non-TNFi (OR = 0.93; 95% CI = 0.54-1.62), via nonbiologic DMARD addition (OR = 0.95; 95% CI = 0.83-1.11), or corticosteroid addition (OR = 1.09; 95% CI = 0.92-1.88). No differences were observed for hospitalization (OR = 1.16; 95% CI = 0.99-1.37) or emergency department visits (OR = 1.02; 95% CI = 0.89-1.18). CONCLUSIONS: No differences were found between a second TNFi vs a non-TNFi. As a result, choice of TNFi or non-TNFi following an initial TNFi may be driven by relevant patient-specific considerations. At the population level, policies that prefer either TNFi or non-TNFi appear reasonable. DISCLOSURES: The study was funded by Humana Inc. Mr Racsa is an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc. Drs Asante and Bloomfield are employees of Humana Inc. Dr Schwab was an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc., and is now an employee of RTI Health Solutions. Dr Cornett was an employee of Humana Inc. and is now an employee of ImmunoGen Inc.

Does the Type of Failure and the Choice of the Second Biologic Influence Response and Persistence on Medication in Rheumatoid Arthritis?

The type of failure may predict response to a second biologic. We evaluated the response to a second tumor necrosis factor inhibitor (TNFi) or non-TNFi in patients failing their initial TNFi, either primarily or secondarily. Patients with rheumatoid arthritis who were biologic-naive and had a Clinical Disease Activity Index (CDAI) >10, who started their first TNFi for ≥3 months and then switched to a second biologic, were included in the study. Secondary failure was defined as 2 consecutive low-CDAI visits and then switching to a second biologic while they had moderate/severe CDAI. Primary failure was defined if it did not meet the definition of secondary failure, or if they had at least 1 moderate/severe CDAI after 3 months on treatment. We used multivariable logistic regression comparing primary versus secondary failure for achievement of CDAI ≤10 (primary outcome) and minimal clinically important differences (secondary outcome) at 6 months after switch. Of the 462 patients included, 64.3% and 35.7% stopped the first TNFi because of a primary and secondary failure, respectively. Patients with primary failure had a more severe disease (CDAI mean, 26.39 vs. 21.61; p < 0.001). The likelihood of achieving CDAI ≤10 (odds ratio, 4.367; 95% confidence interval, 2.428-7.856) and minimal clinically important difference (odds ratio, 2.851; 95% confidence interval, 1.619-5.020) was significantly higher for secondary than primary failure regardless of choice of a second agent. Patients with rheumatoid arthritis with secondary failure to a first TNFi responded better to a second biologic agent, regardless of the choice of biologic.

Tumor necrosis factor inhibitor (TNFi) persistence and reasons for discontinuation in a predominantly male cohort with axial spondyloarthritis

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12months; 63.5% and 47.1% at 24 and 36months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

P091 Switching to TNFi versus non-TNFi biologics in Crohn’s Disease patients: Real-world outcomes from a German claims data analysis

Abstract Background Determining the best treatment path for Crohn’s Disease (CD) patients following loss of response (LoR) to a tumour necrosis factor inhibitor (TNFi) is challenging for clinicians. This study seeks to provide real-world evidence on treatment failure, treatment discontinuation and corticosteroid-free drug survival in CD patients with LoR to a first TNFi, switching to another TNFi compared to a non-TNFi biologic. Methods Adult CD-patients without biologics therapy in the last 6 months who started treatment with adalimumab or infliximab and switched due to LoR to another biologic between 01/10/2014–31/12/2018 were identified from German claims data (AOK PLUS). The identified patients were classified as either within-class switchers (WCS) (if they switched to adalimumab or infliximab) or outside-class switchers (OCS) (if they switched to vedolizumab or ustekinumab). The date of first treatment switch was set as the index date. Patients were followed for at least one year after treatment switch. To compare WCS and OCS, baseline covariate adjustment through inverse probability of treatment weighting (IPTW) of the propensity scores was conducted. Time-to-event analyses were performed using Cox Proportional Hazard regressions adjusted for an indicator of primary non-response and secondary LoR (if the first switch happened within or after 6 months from the initial TNFi). Results 112 patients (53 WCS and 59 OCS) were identified. Upon IPTW, 43 WCS and 54 OCS satisfying the common support assumption were included for comparative analyses with adjustment for primary non-response and secondary LoR. WCS were significantly more likely to receive corticosteroid therapy, more likely to fail and to discontinue the treatment they had switched to; and more likely to switch again to another biologic compared to OCS (Figure 1). Having switched due to primary non-response or due to secondary LoR was not significantly associated with any outcome. Figure 1: Kaplan-Meier curves and Cox proportional hazard models adjusted for an indicator variable of primary non-response/secondary loss of response Abbreviations: CD, Crohn’s disease; CI, confidence interval; HR, hazard ratio Conclusion Whilst small sample size is a limitation, these results suggest that following loss of response to a TNFi, patients may benefit from switching to vedolizumab or ustekinumab rather than switching to a different TNFi.

Cost-utility analysis of treatment options after initial tumor necrosis factor inhibitor therapy discontinuation in patients with rheumatoid arthritis.

BACKGROUND: For patients with rheumatoid arthritis (RA) who discontinued initial treatment with tumor necrosis factor inhibitor (TNFi), 2 approaches are commonly used: cycling to another TNFi or switching to a drug with another mechanism of action. Currently, there is no consensus on which approach to use first. A report from the IBM MarketScan Research administrative claims database showed adalimumab (cycling strategy) and abatacept (switching strategy) were more commonly prescribed after the first TNFi discontinuation. OBJECTIVE: To evaluate the cost-utility of adalimumab versus abatacept in patients with RA whose initial TNFi therapy failed. METHODS: A probabilistic cost-utility microsimulation state-transition model was used. Our target population was commercially insured adults with RA, the time horizon was 10 years, and we used a payer perspective. Patients not responding to adalimumab or abatacept were moved to the next drug in a sequence of 3 and, finally, to conventional synthetic therapy. Incremental cost-utility ratios (2016 USD per quality-adjusted-life-year gained [QALY)] were calculated. Utilities were derived from a formula based on the Health Assessment Questionnaire Disability Index and age-adjusted comorbidity score. RESULTS: Switching to abatacept after the first TNFi showed an incremental cost of just more than $11,300 over 10 years and achieved a QALY benefit of 0.16 compared with adalimumab. The incremental cost-effectiveness ratio was $68,950 per QALY. Scenario analysis produced an incremental cost-effectiveness ratio range of $44,573 per QALY to $148,558 per QALY. Probabilistic sensitivity analysis showed that switching to abatacept after TNFi therapy failure had an 80.6% likelihood of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. CONCLUSIONS: Switching to abatacept is a cost-effective strategy for patients with RA whose discontinue initial therapy with TNFi. DISCLOSURES: Funding for this project was provided by a Rheumatology Research Foundation Investigator Award (principal investigator: Maria A. Lopez-Olivo). Karpes Matusevich's work was supported by a Doctoral Dissertation Research Award from the University of Texas, School of Public Health Office of Research. Lal reports competing interests outside of the submitted work (employed by Optum). Suarez-Almazor reports competing interests outside of the submitted work (consulting fees from Pfizer, AbbVie, Eli Lilly, Agile Therapeutics, Amag Pharmaceuticals, and Gilead). Chan, Swint, and Cantor have nothing to disclose.

Cost-Effectiveness of Treatment Strategies with Biologics in Accordance with Treatment Guidelines for Ankylosing Spondylitis: A Patient-Level Model.

Ankylosing spondylitis (AS) is a form of rheumatic disease caused by chronic inflammation of the axial skeleton. Patients with AS experience significant functional limitations and reduced quality of life. Consequently, AS imposes a substantial economic burden on society due to productivity loss and work disability. Biologics, including tumor necrosis factor (TNF) inhibitors and human anti-interleukin-17A monoclonal antibody (IL-17A) agents, are effective treatment strategies in relieving symptoms and slowing down disease progression. Currently, 5 TNF inhibitors and 2 IL-17A antibody agents are approved by the FDA for the management of AS. Of these agents, there is no clear preferred agent in initial biologic therapy, although an IL-17A antibody agent or alternative TNF inhibitor agent is recommended after failure of the initial TNF inhibitor therapy. To assess cost-effectiveness of treatment strategies with biologics, TNF inhibitor or IL-17A, in accordance with the treatment guidelines for patients with AS. An economic patient-level simulation combining decision-tree and Markov models was constructed from the U.S. health care payer's perspective over a 10-year time horizon. The current model examined 5 treatment strategies: (1) conventional care treatment with nonsteroidal anti-inflammatory drugs, (2) 1 TNF inhibitor, (3) an IL-17A antibody agent, (4) sequential therapy with 2 TNF inhibitors, and (5) sequential therapy with a TNF inhibitor followed by an IL-17A antibody agent. Initially, treatment responses were determined after 12-week treatments. Patients who responded to treatment entered a "responders" Markov model. Patients entered a "nonresponders" Markov model if they inadequately responded to treatment. In sequential treatment strategies, patients who inadequately responded to treatment with the first TNF inhibitor received a second TNF inhibitor or an IL-17A antibody agent. Health utility was estimated based on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI) scores. The models accounted for real-world adherence to TNF inhibitor treatment. Scenario and probabilistic sensitivity analyses were performed to test the robustness and uncertainty of the model results. Over a 10-year time horizon and 100,000 simulated patients for each treatment strategy, base-case results produced average total discounted per-patient costs of $19,765, $130,302, $159,934, $190,553, and $179,118 and quality-adjusted life-years (QALYs) of 4.675, 5.410, 5.499, 5.919, and 5.893 for conventional care, treatment strategies with 1 TNF inhibitor, an IL-17A, 2 TNF inhibitors, and a TNF inhibitor followed by an IL-17A, respectively. The optimal treatments at willingness-to-pay (WTP) thresholds ≤ $130,813 per QALY, between $130,813 per QALY and $442,728 per QALY, and > $442,728 per QALY were conventional care and sequential treatment strategies with 1 TNF inhibitor, followed by an IL-17A agent and 2 TNF inhibitors, respectively. Study findings suggested that all treatment strategies with biologics, TNF inhibitors or IL-17A antibody agents, in the treatment guidelines for AS were not cost-effective at the common WTP of $100,000 per QALY. However, the sequential treatment with 1 TNF inhibitor followed by an IL-17A antibody agent was considered cost-effective at a higher WTP of $150,000 per QALY. No outside funding supported this study. The authors have nothing to disclose. Primary findings of this study were presented in part at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in Baltimore, MD, May 2018.

Efficacy predictors of a second tumor necrosis factor inhibitor in the treatment of rheumatoid arthritis.

To retrospectively evaluate initial tumor necrosis factor inhibitor (TNFi) failure patients for clinical predictors of response to a 2nd TNFi in our 4282 rheumatoid arthritis (RA) patient database.A cross-sectional retrospective manual chart review of the electronic health record (EHR) was performed on 322 “real world” RA patients who were prescribed 2 TNFis. Response to TNFi was determined by the treating provider who had real time Clinical Disease Activity Index (CDAI) scores to inform treatment decisions. Age, gender, body mass index (BMI), insurance provider, duration of disease, cyclic citrullinated peptide antibody (CCP) and rheumatoid factor (RF) positivity, concomitant disease modifying anti-rheumatic drug therapy, length of time between diagnosis and start of 1st and 2nd TNFi, transient efficacy of 1st TNFi (defined as response to TNFi at 3 months but later lost response), and reason for discontinuation of 1st TNFi were analyzed. A multivariable logistic regression model was used to model response to a 2nd TNFi.Response proportions to the 2nd TNFi were greater in females (161/223, 72.2% response female vs 41/75, 54.7% male, P < .01), those who began their 1st TNFi within 3 months of their RA diagnosis, and in RF+ patients (123/170, 72.4% response seropositive vs 66/110, 60.0% seronegative, P < .03). The higher female response rate was independent of age, BMI, and seropositivity.In RA patients who failed an initial TNFi, female patients and patients with RF+ were more likely to have a clinical response to a 2nd TNFi. In the absence of these predictors, stronger consideration for choosing a biologic with an alternative mechanism of action might be given when the 1st TNFi fails.

PMS28 COST-UTILITY ANALYSIS OF TREATMENT OPTIONS AFTER INITIAL TUMOR NECROSIS FACTOR INHIBITOR THERAPY FAILURE IN PATIENTS WITH RHEUMATOID ARTHRITIS

To use real-world data to analyze the cost-utility of sequences of therapeutic drugs used by rheumatoid arthritis patients whose initial tumor necrosis factor inhibitor therapy failed. We developed a microsimulation Markov model to analyze 10,000 rheumatoid arthritis patients (80% female, mean age 52yrs) beginning their second biological treatment with adalimumab (cycling) or abatacept (swapping) and followed them for 10 years or until death. Patients not responding switched to the next drug in a sequence of three (adalimumab-abatacept-tocilizumab versus abatacept-tocilizumab-rituximab) and then shifted to palliative treatment. Demographics, the most common drug choice per cycling or swapping cohorts, subsequent treatment sequences, direct medical costs, and transition probabilities were derived from a cohort of rheumatoid arthritis patients in the 2008-2016 Truven Health MarketScan Research database. Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) were derived from an age-adjusted comorbidity index and converted to utilities using the formula from the Birmingham Rheumatoid Arthritis Model. Scenario analysis was used to vary the time horizon, utility formula and baseline HAQ-DI. We also performed a probabilistic sensitivity analysis. Swapping to a sequence beginning with abatacept showed an incremental discounted cost of $11,357 over ten years and achieved a discounted cost per quality-adjusted life year (QALY) benefit of 0.16 compared with cycling to adalimumab. The incremental cost-effectiveness ratio of $68,950/QALY was within current willingness-to-pay thresholds. Scenario analysis produced an incremental cost-effectiveness ratio range of $44,573/QALY to $148,558/QALY: abatacept was more cost-effective over longer periods of time and when baseline HAQ was lower. Probabilistic sensitivity analysis showed that swapping to abatacept after tumor necrosis factor inhibitor therapy failure had an 80.6% likelihood of being cost-effective at $100,000/QALY. Abatacept is a cost-effective strategy for rheumatoid arthritis patients whose initial tumor necrosis factor inhibitor therapy fails. Being able to stratify patients by reason for switch would improve the validity of our conclusions.

Frequency of biologic switching and the outcomes of switching in children and young people with juvenile idiopathic arthritis: a national cohort study.

SummaryBackgroundInformation is scarce about biological disease-modifying antirheumatic drug (DMARD) switching patterns in children and young people (aged ≤16 years) with juvenile idiopathic arthritis in an era of many biologic therapies. The best choice of biologic to use if the first biological DMARD is not beneficial also remains unclear. We aimed to quantify and characterise biologic switching patterns in children and young people with juvenile idiopathic arthritis, and to compare the effectiveness of using a second tumour necrosis factor inhibitor (TNFi) versus non-TNF is following failure of a first TNFi biologic in routine clinical practice.MethodsOur study population comprised patients with juvenile idiopathic arthritis who were enrolled in two parallel UK cohort studies (the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study [BSPAR-ETN] and the Biologics for Children with Rheumatic Diseases [BCRD] study) between Jan 1, 2004, and April 11, 2019. Data on disease characteristics and DMARD therapy were collected at the time of initiation of a first biologic, at 6 months, at 1 year, and annually thereafter. Biologic switching patterns were described in all patients who started their first biologic from Jan 1, 2010, onwards. Among patients who started treatment with their first biologic from Jan 1, 2004, onwards, had polyarticular course juvenile idiopathic arthritis (extended oligoarthritis or polyarthritis [positive or negative for rheumatoid factor]), and who had started a second biologic, we assessed changes in outcome variables at 6 months compared with baseline and compared the proportion of patients who achieved an American College of Rheumatology Pediatric (ACR Pedi) 90 response and minimal disease activity at 6 months on the basis of the class of the second biologic (a second TNFi vs non-TNFi biologic). Changes in outcome variables at 6 months were compared using linear regression or logistic regression, adjusted for propensity quintiles to account for confounding by indication. We used multiple imputation to account for missing data.FindingsBetween Jan 1, 2004, and April 11, 2019, 2361 patients were enrolled on initiation of biologic therapy. From Jan 1, 2010, onwards, 1152 patients started their first biologic, most of whom started treatment with TNFis (1050 [91%]). The median follow-up was 2·2 years (IQR 1·1–3·8). During this time, 270 (23%) of 1152 patients started a second biologic, 61 (5%) started a third biologic, and 11 (1%) started a fourth biologic. Among 240 patients with polyarticular-course juvenile idiopathic arthritis, 194 (81%) started a second TNFi and 46 (19%) started a non-TNFi after an initial TNFi had failed. Choice of second treatment (second TNFi vs non-TNFi biologic) did not affect the proportion of patients who achieved an ACR Pedi 90 response (adjusted odds ratio [OR] 2·5, 95% CI 0·8–7·9; p=0·11) or minimal disease activity (adjusted OR 1·6, 95% CI 0·6–3·8; p=0·33).InterpretationFor many children and young people with juvenile idiopathic arthritis, treatment with a first or second biologic is not beneficial. We found no evidence that switching to a second non-TNFi biologic was more beneficial than a second TNFi.FundingVersus Arthritis and The British Society for Rheumatology.

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

IntroductionPatients 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).MethodsAdults 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).ResultsOf 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).ConclusionsPatients 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.FundingAbbVie.

Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis

ObjectivesTo compare responses in patients with early rheumatoid arthritis (RA) initially treated with the tumour necrosis factor inhibitor (TNFi) adalimumab+methotrexate (MTX) versus MTX monotherapy who may have continued receiving MTX...

Clinical Outcomes and Biologic Costs of Switching Between Tumor Necrosis Factor Inhibitors in US Veterans with Rheumatoid Arthritis.

IntroductionThe purpose of this study was to evaluate clinical outcomes and drug/administration costs of treatment with tumor necrosis factor inhibitor (TNFi) agents in US veterans with rheumatoid arthritis (RA) initiating TNFi therapy. The analysis compared patients initiating and continuing a single TNFi with patients who subsequently switched to a different TNFi.MethodsData from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry who initiated treatment with adalimumab, etanercept, or infliximab from 2003 to 2010 were analyzed. Outcomes included duration of therapy, Disease Activity Score based on 28 joints (DAS28), and direct drug and drug administration costs.ResultsOf 563 eligible patients, 262 initiated a single TNFi therapy, 142 restarted their initial TNFi after a ≥90-day gap in treatment (interrupted therapy), and 159 switched to a different TNFi. Patients who switched had higher mean DAS28 before starting TNFi therapy than patients with single or interrupted therapy: 5.3 vs 4.5 or 4.6, respectively. Mean duration of the first course was 34.3 months for single therapy, 18.3 months for interrupted therapy, and 17.7 months for switched therapy. Mean post-treatment DAS28 was highest for patients who switched TNFi. Mean annualized costs for first course were $13,800 for single therapy, $13,200 for interrupted therapy, and $14,200 for switched therapy; mean annualized costs for second course were $12,800 for interrupted therapy and $15,100 for switched therapy.ConclusionPatients who switched TNFi had higher pre-treatment DAS28 and higher overall costs than patients who received the same TNFi as either single or interrupted therapy.FundingThis research was funded by Immunex Corp., a fully owned subsidiary of Amgen Inc., and by VA HSR&D Grant SHP 08-172.

Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial

Tumour necrosis factor (TNF) inhibition and B-cell depletion are highly effective treatments for active rheumatoid arthritis, but so far no randomised controlled trials have directly compared their safety, efficacy, and cost-effectiveness. This study was done to test the hypothesis that using rituximab would be clinically non-inferior and cheaper compared with TNF inhibitor treatment in biological-treatment naive patients with rheumatoid arthritis. This open-label, randomised controlled, non-inferiority trial enrolled patients with active, seropositive rheumatoid arthritis and an inadequate response to synthetic disease modifying anti-rheumatic drugs (DMARDs) from 35 rheumatology departments in the UK. Patients were randomly assigned 1:1 to the rituximab or TNF inhibitor groups with minimisation to account for methotrexate intolerance using a web-based randomisation system. Patients were given intravenous rituximab 1 g on days 1 and 15, and after 26 weeks if they responded to treatment but had persistent disease activity (28 joint count disease activity score [DAS28-ESR] >3.2; rituximab group) or a TNF inhibitor-adalimumab (40 mg subcutaneously every other week) or etanercept (50 mg per week subcutaneously) according to the patient's and rheumatologist's choice (TNF inhibitor group). Patients could switch treatment in the case of drug-related toxic effects or absence or loss of response. The primary outcome measure was the change in DAS28-ESR between 0 and 12 months in the per-protocol population of patients who were assigned to treatment and remained in follow-up to 1 year. We assessed safety in all patients who received at least one dose of study drug. We also assessed the cost-effectiveness of each strategy. The non-inferiority margin was specified as 0.6 DAS28-ESR units. This study is registered with ClinicalTrials.gov, number NCT01021735. Between April 6, 2009, and Nov 11, 2013, 295 patients were randomly assigned and given either rituximab (n=144) or TNF inhibitor (n=151) treatment. After 12 months, the change in DAS28-ESR for patients assigned to rituximab was -2.6 (SD 1.4) and TNF inhibitor was -2.4 (SD 1.5), with a difference within the prespecified non-inferiority margin of -0.19 (95% CI -0.51 to 0.13; p=0.24). The health-related costs associated with the rituximab strategy were lower than the TNF inhibitor strategy (£9,405 vs £11,523 per patient, p<0.0001). 137 (95%) of 144 patients in the rituximab group and 143 (95%) of 151 patients in the TNF inhibitor group had adverse events. 37 serious adverse events occurred in patients receiving rituximab compared with 26 in patients receiving TNF inhibitors, of which 27 were deemed to be possibly, probably, or definitely related to the treatment (15 vs 12, p=0.5462). One patient in each group died during the study. Initial treatment with rituximab is non-inferior to initial TNF inhibitor treatment in patients seropositive for rheumatoid arthritis and naive to treatment with biologicals, and is cost saving over 12 months. Arthritis Research UK, Roche.

Impact of Switching From an Initial Tumor Necrosis Factor Inhibitor on Health Care Resource Utilization and Costs Among Patients With Rheumatoid Arthritis

PurposeDespite improved clinical outcomes for the majority of patients, nearly 30% of patients with rheumatoid arthritis (RA) who initiate tumor necrosis factor antagonist (anti-TNF) biologic agents fail to respond to their first-line anti-TNF and switch to another anti-TNF or a non-TNF biologic. How this change affects health care costs and resource utilization is unknown. We therefore compared RA patients taking first-line anti-TNFs who switched to a second anti-TNF versus those patients who switched to an alternate biologic. MethodsHealth care claims data were obtained from a large US database for eligible adults with confirmed RA diagnoses who initiated anti-TNF treatment and switched to another biologic. Health care costs and utilization during the first 12 months’ postswitch were compared. Generalized linear models were used to adjust for differences in demographic and clinical characteristics before switching. FindingsPatients who switched to a second anti-TNF rather than a non-TNF biologic were generally younger (53.0 vs. 55.3 years; P < 0.0001) and less likely to be female (79.7% vs. 82.7%; P = 0.0490). Of the 3497 eligible patients who switched from first-line anti-TNFs, 2563 (73.3%) switched to another anti-TNF and 934 (26.7%) switched to a non-TNF. Adalimumab was the most frequently prescribed (43.4%) second-line anti-TNF, and abatacept was the most common non–anti-TNF (71.4%). Patients who switched to a second anti-TNF remained on their first medication for a significantly shorter period (342.5 vs 420.6 days; P < 0.0001) and had lower comorbidity indices and higher disease severity at baseline than those who switched to a non–anti-TNF. After adjusting for baseline differences, patients who switched to second anti-TNFs versus a non-TNF incurred lower RA-related costs ($20,938.9 vs $22,645.2; P = 0.0010) and total health care costs ($34,894.6 vs $38,437.2; P = 0.0010) 1 year postswitch. These differences were driven by increased physician office visit costs among the non-TNF group. ImplicationsAmong the anti-TNF initiators who switched therapy, more patients switched to a second anti-TNF than to a non-TNF. Switching to a second anti-TNF treatment was associated with lower all-cause and RA-related health care costs and resource utilization than switching to a non-TNF. Because switching therapy may be unavoidable, finding a treatment algorithm mitigating this increase to any extent should be considered. These data are limited by their retrospective design. Additional confounding variables that could not be controlled for may affect results.

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study

ObjectivesTo compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi.MethodsSWITCH-RA was...

FRI0200 Relative effectiveness of rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis and an inadequate response to a single previous TNF inhibitor: Results from switch-RA, a global, comparative-effectiveness, observational study

BackgroundRecent studies indicate that RA patients (pts) with an inadequate response (IR) to a tumor necrosis factor inhibitor (TNFi) may achieve greater clinical benefit from switching to rituximab (RTX) than...

Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review.

Conventional disease-modifying antirheumatic drugs such as methotrexate are the mainstay of treatment for rheumatoid arthritis. More recently, biologic agents such as etanercept, infliximab and adalimumab, which act by inhibiting tumour necrosis factor (TNF), have become available. TNF inhibitors have proved to be very effective in patients not responding to conventional disease-modifying antirheumatic drugs. However, about 20% to 40% of patients treated with a TNF inhibitor fail to achieve a 20% improvement in American College of Rheumatology criteria, and more lose response over time (secondary failure or acquired therapeutic resistance) or experience adverse events following treatment with a TNF inhibitor. In this group of patients, therapeutic options were limited until recently and an established treatment approach was to switch from one TNF inhibitor to another. In recent years, therapeutic options in these patients have increased with the introduction of biologic agents with novel mechanisms of action, such as rituximab and abatacept. This review outlines the current evidence in support of the available treatment strategies in patients with an inadequate response or intolerance to an initial TNF inhibitor.