Treatment patterns and clinical outcomes in patients with rheumatoid arthritis initiating etanercept, adalimumab, or Janus kinase inhibitor as first-line therapy: results from the real-world CorEvitas RA Registry.

BACKGROUND: Real-world studies assessing the comparative effectiveness of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) as first-line targeted therapy are scarce. We analyzed the real-world persistence and effectiveness of etanercept (ETN), adalimumab (ADA), and Janus kinase inhibitors (JAKis) as first-line therapy in b/tsDMARD-naïve patients with rheumatoid arthritis (RA). METHODS: Adults (≥ 18 years) enrolled in the CorEvitas RA Registry and initiating ETN, ADA, or a JAKi (alone or in combination with csDMARDs) between November 2012 and June 2021 were included if they had 6 and/or 12 months' follow-up. Treatment persistence and effectiveness outcomes including the change in Clinical Disease Activity Index (CDAI) and patient-reported outcomes (PROs) were evaluated at follow-up, adjusting for covariates using linear and logistic regression models. An exploratory analysis for patients on monotherapy was also conducted. RESULTS: Of 1059 ETN, 1327 ADA, and 581 JAKi initiators; 803 ETN, 984 ADA, and 361 JAKi initiators had 6 months' follow-up. JAKi initiators were older and had a relatively longer disease duration than ETN or ADA initiators (mean age: 61.3 vs 54.5 and 55.5 years; mean duration of RA: 8.1 vs 5.7 and 5.6 years). Unadjusted mean improvements in CDAI and PROs were similar between the groups at 6 months, except the proportion achieving LDA, remission, and MCID in CDAI, which were numerically higher in the ETN and ADA groups vs JAKi group (LDA: 43.4% and 41.9% vs 32.5%; remission: 18.2% and 15.1% vs 11.5%; MCID: 46.5% and 47.8% vs 38.0%). Adjusted effectiveness results did not reveal statistically significant differences between treatment groups at 6 months, with an exception in MCID (odds ratio [95% CI] for JAKi vs ETN: 0.65 [0.43-0.98]). At 6 months, 68.2% of ETN, 68.5% of ADA, and 66.5% of JAKi initiators remained on therapy. The findings at 12 months' follow-up and sensitivity analysis among monotherapy initiators also showed no differences in effectiveness outcomes between the groups. CONCLUSIONS: This analysis of real-world data from the CorEvitas RA Registry did not show differences in clinical effectiveness and treatment persistence rates in b/tsDMARD-naïve patients initiating ETN, ADA, or JAKi as first-line targeted therapy either alone or in combination with csDMARDs.

Real-World Evidence Assessing Psoriatic Arthritis by Disease Domain: An Evaluation of the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: Real-world studies assessing treatment response by psoriatic arthritis (PsA) domains are limited. This study aimed to describe the patient characteristics, frequency and combinations of disease domains, disease activity, and patient-reported outcomes (PROs) by PsA domains in patients who initiated treatment with a tumor necrosis factor inhibitor (TNFi) or interleukin-17 inhibitor (IL-17i). METHODS: Adults with PsA who initiated treatment with a TNFi or an IL-17i between January 2013 and January 2021 and had a 6 (±3)-month follow-up were included. The prevalence of PsA domains, the most common domain combinations, treatment persistence, and unadjusted change in disease activity and PROs from baseline to 6 months for each PsA domain were summarized descriptively. RESULTS: Of the 1005 eligible patients, 63% were receiving TNFi and 37% were receiving IL-17i. Forty percent of TNFi and 14% of IL-17i initiators received these treatments as first-line therapy. Peripheral arthritis and skin disease were the most common PsA domains identified in 86% and 82% of patients, respectively, and the triad of peripheral arthritis, skin disease, and nail psoriasis was the most common domain combination observed in 14% of patients. More than two thirds (68%) of patients remained on therapy at 6 months' follow-up. Improvements in disease activity and PROs were observed across all PsA domains in those receiving TNFi or IL-17i. CONCLUSION: This real-world analysis highlights the heterogeneity in domain presentation; therefore, assessing all PsA domains is important for optimal disease management. Improvements in outcomes across all PsA domains demonstrate the effectiveness of TNFi and IL-17i in diverse patient groups exhibiting different phenotypes of PsA.

Factors Associated With Maintenance of Remission Following Change From Combination Therapy to Monotherapy in Patients With Rheumatoid Arthritis.

OBJECTIVE: Some patients with rheumatoid arthritis (RA) who persist in remission may decide to stop their therapy. We evaluated baseline characteristics associated with remaining in remission or low disease activity (LDA) following medication withdrawal. METHODS: The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis (SEAM-RA) was a phase III, multicenter, randomized withdrawal, double-blind, controlled study in patients with RA on methotrexate (MTX) + etanercept (ETN). If remission (Simplified Disease Activity Index [SDAI] ≤ 3.3) was sustained through a 24-week run-in period, patients then entered a 48-week double-blind period and were randomized 2:2:1 to receive MTX monotherapy, ETN monotherapy, or continue combination therapy. Multivariate logistic regression analysis was performed to identify baseline factors associated with remission or LDA at the end of both periods. RESULTS: Of 371 patients enrolled, 253 entered the double-blind period. After adjusting for other factors, covariates associated with achieving SDAI remission at the end of the run-in period included younger age, longer duration of MTX treatment, and less severe clinical disease variables. Covariates associated with maintaining remission/LDA at the end of the 48-week double-blind period included lower patient global assessment of disease activity (PtGA), lower C-reactive protein, rheumatoid factor (RF) negativity, longer RA duration in the MTX arm, shorter duration of ETN treatment, and lower magnesium. CONCLUSION: These findings indicate patients with overall lower disease activity are more likely to remain in SDAI remission/LDA after switching from combination therapy to monotherapy. RF-negative status and lower PtGA scores were strongly associated with increased likelihood of remaining in remission/LDA with MTX or ETN monotherapy. (SEAM-RA; ClinicalTrials.gov: NCT02373813).

Effects of Disease-Worsening Following Withdrawal of Etanercept or Methotrexate on Patient-Reported Outcomes in Patients With Rheumatoid Arthritis: Results From the SEAM-RA Trial.

BACKGROUND/OBJECTIVE: The effect of treatment withdrawal on patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) whose disease is in sustained remission has not been well described. This analysis aimed to compare PRO changes in patients with RA following medication withdrawal and disease worsening. METHODS: SEAM-RA (Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis) was a phase 3, multicenter, randomized withdrawal, double-blind controlled study in patients with RA taking methotrexate plus etanercept and in remission (Simple Disease Activity Index ≤3.3). Patient's Global Assessment of Disease Activity, Patient's Assessment of Joint Pain, Health Assessment Questionnaire-Disability Index, and 36-Item Short-Form Health Survey were evaluated for 48 weeks following methotrexate or etanercept withdrawal. Treatment differences for patients with versus without disease worsening were evaluated using a 2-sample t test for continuous end points and log-rank test for time-to-event end points. RESULTS: Of 253 patients, 121 experienced disease worsening and 132 did not. All PRO scores were similar to those of a general population at baseline and deteriorated over time across the study population. The PtGA and Patient's Assessment of Joint Pain values deteriorated less in those on etanercept monotherapy compared with methotrexate monotherapy. More patients with versus without disease worsening experienced deterioration that was greater than the minimal clinically important difference (MCID) for all PROs tested. In patients with disease worsening, PtGA deterioration more than the MCID preceded Simple Disease Activity Index disease worsening. CONCLUSIONS: Etanercept monotherapy showed benefit over methotrexate in maintaining PRO scores. Patients with disease worsening experienced a more rapid worsening of PtGA beyond the MCID versus patients without disease worsening.Categories: autoinflammatory disease, biological therapy, DMARDs, rheumatoid arthritis.

Potential Impact of Sex and BMI on Response to Therapy in Psoriatic Arthritis: Post Hoc Analysis of Results From the SEAM-PsA Trial.

OBJECTIVE: In this post hoc analysis, we examined the potential impact of sex and BMI on response in the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) trial (NCT02376790), a 48-week, phase III, randomized controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept (ETN) monotherapy, and MTX+ETN combination therapy in patients with psoriatic arthritis (PsA) who were naïve to MTX and biologics. METHODS: We evaluated key outcomes at week 24 stratified by sex (male vs female) and BMI (kg/m2; ≤ 30 vs > 30), including the American College of Rheumatology 20 (ACR20) criteria, minimal disease activity (MDA), very low disease activity (VLDA), and Psoriatic Arthritis Disease Activity Score (PASDAS). We analyzed data using descriptive statistics, normal approximation, logistic model, and analysis of covariance. RESULTS: A total of 851 patients completed the SEAM-PsA trial. Higher proportions of men than women who received MTX+ETN combination therapy achieved ACR20 (71.5% vs 58.3%; P = 0.02), MDA (45.8% vs 25.2%; P = 0.0003), and VLDA (19.1% vs 9.5%; P = 0.03), and men achieved better PASDAS (-3.0 vs -2.3; P = 0.0004). Patients with BMI ≤ 30 generally had better outcomes than those with BMI > 30 in some treatment arms for ACR20, MDA, VLDA, and PASDAS; however, there was no consistent pattern regarding the treatment arm in which the difference occurred. CONCLUSION: Improved outcomes were observed more in men than in women for MDA and PASDAS with MTX+ETN combination therapy. Patients with BMI ≤ 30 had better outcomes than those with BMI > 30, with no clear pattern regarding treatment received. These findings suggest that contextual factors such as sex and BMI may affect response to PsA therapy.

Biologic and Targeted Synthetic DMARD Utilization in the United States: Adelphi Real World Disease Specific Programme for Rheumatoid Arthritis.

INTRODUCTION: In patients with inadequate response or intolerance to first biologic disease-modifying antirheumatic drug (bDMARD), guidelines recommend switching to an agent of different mechanism of action or to another bDMARD. However, the reasons behind switching between bDMARD/targeted synthetic (ts)DMARD are not well documented in many studies. The objective of this study was to assess the rheumatologists' perceptions and behaviors towards choice of initial b/tsDMARD treatment and reasons for switching between bDMARDs/tsDMARDs, in the context of present treatment patterns. METHODS: This was a retrospective analysis of data collected from the 12th Adelphi Real World Disease Specific Programme for rheumatoid arthritis (RA). Qualified rheumatologists involved in treatment decision-making for ≥ 10 patients a month completed patient record forms (PRFs). Patients aged ≥ 18 years with RA diagnosis and receiving bDMARD/tsDMARD were included. The outcomes assessed were proportion of patients receiving bDMARD/tsDMARD at molecule and class levels; rheumatologist-reported reasons for choice of therapy; proportion of patients who switched bDMARDs/tsDMARDs; and rheumatologist-reported reasons for switching therapies. RESULTS: Eighty-six rheumatologists completed PRFs for 1027 patients. Of these, 621 were receiving bDMARD/tsDMARD at data collection. The majority (73%) of patients received first-line bDMARD/tsDMARD, and at first-line, 68% received a tumor necrosis factor inhibitor (TNFi) and 21% received a Janus kinase inhibitor (JAKi). The response option of strong overall efficacy was the primary reason for selecting first-line and second-line bDMARD/tsDMARD. A total of 163 patients had switched from first-line b/tsDMARD to second-line b/tsDMARD therapy. Of these, 44, 28, and 17% had switched from TNFi to another TNFi, TNFi to non-TNF biologic, and TNFi to JAKi, respectively. Lack of efficacy and worsening disease were the most frequent reasons for switching therapies. CONCLUSIONS: TNFis remain the most prescribed b/tsDMARD for first-line and second-line treatments. Strong overall efficacy was the primary reason for selecting therapy and loss of efficacy was the primary reason for switching therapy.

Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conventional synthetic disease-modifying antirheumatic drug therapy and enrolled in a North American clinical registry.

BACKGROUND: Understanding the evolving treatment patterns in patients with rheumatoid arthritis (RA) is important for rheumatologists to make the best practice decisions and optimize treatment. Here, we describe treatment patterns among patients newly initiated on biologic and/or nonbiologic RA therapy over time after enrollment in the US Corrona RA registry. METHODS: This was a retrospective, cohort study of adult patients with RA enrolled in the Corrona RA registry. Patients were included in this study if they initiated therapy with conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, TNF inhibitor (TNFi) monotherapy, other (non-TNFi) biologic monotherapy, or combination therapy (index therapy); initiated therapy between January 1, 2004, and December 31, 2015 (index date), after enrollment in the Corrona RA registry; had at least 6 months of follow-up time after the index date; and had at least one follow-up visit. Time periods of interest were based on the year of index therapy initiation: 2004-2007, 2008-2011, and 2012-2015. RESULTS: This study included 8027 patients. csDMARD monotherapy and TNFi + csDMARD combination therapy were the most common index therapies in the registry (39.9% and 44.9%, respectively, in the 2004-2007 period; 38.6% and 38.2%, respectively, in the 2008-2011 period; and 35.2% for both in the 2012-2015 period). At therapy initiation, a higher proportion of patients who initiated other biologics, whether as monotherapies (54.0%) or in combination with csDMARD (49.9%), had high disease activity than those who initiated csDMARD monotherapy (28.4%). For 2012-2015 vs 2004-2007 and 2008-2011 periods, persistence on a given therapy appeared to decrease for the TNFi monotherapy cohort (48.2% vs 64.3% and 52.4%) and other biologic monotherapy cohort (52.3% vs 71.4% and 54.5%) over 12 months; switching from one therapy to another was common in the Corrona RA registry. CONCLUSIONS: Increased switching from one therapy to another and decreased time on a given therapy was observed in the Corrona RA registry in the 2012-2015 period. This observation is most likely due to the increased availability of additional treatment options and/or the change in clinical focus, particularly the emphasis on achievement of treat-to-target goals of remission or low disease activity along with more aggressive treatment.

Patient-reported outcomes data in patients with psoriatic arthritis from a randomised trial of etanercept and methotrexate as monotherapy or in combination.

OBJECTIVES: We examined patient-reported outcomes (PROs) in The Study of Etanercept And Methotrexate in Patients with Psoriatic Arthritis (PsA); a 48-week, phase 3, randomised controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept monotherapy, and MTX+ etanercept in patients with PsA. METHODS: Efficacy endpoints included: mean changes from baseline and proportion of patients who reported improvements≥minimal clinically important difference (MCID) at week 24 in treatment groups for Health Assessment Questionnaire-Disability Index, Patient Global Assessment (PtGA), Patient Global Assessment of Joint Pain (PtGAJP) and Medical Outcomes Study Short Form-36 Questionnaire (SF-36) Physical Component Summary (PCS), and Mental Component Summary, and eight domain scores. PROs were analysed as reported (observed), without multiplicity adjustment; therefore, p values are descriptive. RESULTS: At week 24, patients receiving etanercept monotherapy or MTX+ etanercept combination reported greater improvements (p≤0.05) in PtGA, PtGAJP and SF-36 PCS scores compared with those receiving MTX monotherapy. Compared with MTX monotherapy, higher proportions of patients receiving etanercept monotherapy and combination therapy reported improvements≥MCID in PtGA (etanercept vs MTX, p=0.005) and PtGAJP (MTX +etanercept vs MTX, p=0.038). Across PROs, proportions of patients reporting scores≥age and gender-matched normative values at week 24 ranged from 20.8% to 51.0% with MTX monotherapy, 30.9% to 48.8% with etanercept monotherapy, and 30.6% to 52.3% with MTX+ etanercept combination. CONCLUSIONS: Patients receiving etanercept monotherapy or MTX+ etanercept reported greater improvements from baseline in several PROs compared with those receiving MTX monotherapy. PROs should be incorporated in discussions between patients and clinicians regarding their treatment choices as they can help determine which treatments are more beneficial in patients with PsA.

Potential for Major Therapeutic Changes to Produce Significant Clinical Response Across a Broad Range of Disease Activity: An Observational Study of US Veterans With Rheumatoid Arthritis.

OBJECTIVE: To examine the impact of major therapeutic change (MTC) on clinical response across a broad range of disease activity in US veterans with rheumatoid arthritis (RA). METHODS: This historical cohort analysis evaluated patient visits from the Veterans Affairs RA registry between January 1, 2006 and September 30, 2017. Eligible patient visits were a rheumatology visit with 3 disease activity measures, including the Disease Activity Score in 28 joints, the Clinical Disease Activity Index, and the Routine Assessment of Patient Index Data 3; the follow-up visit for all 3 disease activity measures was 2-6 months later. The full population and a subset of patients with active disease (≥6 tender joints, ≥6 swollen joints) were evaluated. Clinical outcome was based on the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20). The effect of MTC on ACR20 response was presented as crude descriptive statistics and evaluated using standardized regression for population- and disease activity-level conditional effects. RESULTS: The full population comprised 1,208 patients (6,138 visits) and the active disease subpopulation included 383 patients (1,109 visits). Overall, visits with MTC were associated with increased likelihood of ACR20 response across all disease activity measures for the full population. Risk ratios for overall risk of ACR20 response for visits with MTC versus those without MTC ranged from 1.67 to 2.22 across disease activity measures among the full population and from 1.51 to 1.60 for the subpopulation with active disease. CONCLUSION: MTC was associated with clinical improvement, even among patients with longstanding RA who had received multiple prior therapies, which emphasizes the utility of therapy modifications for patients with established and active RA.

Performance of composite measures used in a trial of etanercept and methotrexate as monotherapy or in combination in psoriatic arthritis.

OBJECTIVES: To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA. METHODS: The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS). RESULTS: At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments. CONCLUSION: PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden. TRAIL REGISTRATION: https://ClinicalTrials.gov, number NCT02376790.

Juvenile Spondyloarthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry: High Biologic Use, Low Prevalence of HLA-B27, and Equal Sex Representation in Sacroiliitis.

OBJECTIVE: To describe characteristics of children with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (PsA) who were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. METHODS: All children with ERA and those with juvenile PsA were identified. Demographic characteristics, clinical characteristics, and treatments were described. The children with sacroiliitis and those without sacroiliitis were compared. In the children with sacroiliitis, the first visit with clinically active sacroiliitis (which came first in 72% of cases) was compared to the first visit without clinically active sacroiliitis. RESULTS: A total of 902 children with ERA or juvenile PsA were identified. Children with ERA were older at diagnosis (ages 10.8 years versus 8.2 years; P < 0.01) and were more likely to be male (56% versus 38%; P < 0.01). Polyarticular involvement was reported in 57% of children with ERA and in 72% of those with juvenile PsA. Of the children tested, HLA-B27 was positive in 38% of those in the ERA group and in 12% of those in the juvenile PsA group. At least 1 biologic was taken by 72% of those with ERA and 64% of those with juvenile PsA. Sacroiliitis (diagnosed clinically and/or by imaging) was reported in 28% of the children (40% of those with ERA and 12% of those with juvenile PsA). Of these, 54% of the children were female, 36% were HLA-B27 positive, and 81% took at least 1 biologic. In children with sacroiliitis, scores according to the physician global assessment of disease activity, parent/patient global assessment of well-being, and clinical Juvenile Arthritis Disease Activity Score 10 were all significantly worse at the first visit with clinically active sacroiliitis versus the first visit without active sacroiliitis. CONCLUSION: In this registry, there are more than 900 children with ERA or juvenile PsA. There was high biologic use in this population, especially in those with sacroiliitis. Further, there was equal sex representation in those children with sacroiliitis.

Empirical evidence of disease activity thresholds used to indicate need for major therapeutic change in US veterans with rheumatoid arthritis.

BACKGROUND: A previous analysis of the Veterans Affairs Rheumatoid Arthritis (VARA) registry showed that more than half of the patients with rheumatoid arthritis (RA) did not receive a major therapeutic change (MTC) despite moderate or severe disease activity. We aimed to empirically determine disease activity thresholds associated with a decision by rheumatologists and nurse practitioners to institute a MTC in patients with RA and to report the impact of that change on RA disease activity. METHODS: We analyzed data from the VARA registry between January 1, 2006, and September 30, 2017. Eligible patients had a visit with 3 disease activity measures (DAMs) recorded: Disease Activity Score for 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3). The Youden Index was used to identify disease activity thresholds that best discriminated rheumatologist/nurse practitioner decision to initiate MTC. Clinical outcome was 20% improvement in the American College of Rheumatology criteria (ACR20 response). The effect of MTC on ACR20 response was presented as crude descriptive statistics and evaluated using G-computation for marginal and conditional effects with established disease activity level combined with an empirical threshold from Youden analysis. RESULTS: The study population comprised 1776 patients (12,094 visits: 3077 with MTC, 9017 without MTC). Empirical thresholds (95% bootstrap confidence interval with 1000 replications) for MTC were 4.03 (3.70-4.36) for DAS28, 12.9 (10.4-15.4) for CDAI, and 3.81 (3.32-4.30) for RAPID3. Visits with MTC had increased likelihood of ACR20 response: risk ratios for ACR20 response for visits with MTC vs without MTC ranged 1.2-2.6 across DAMs; risk differences ranged 0.2-14.5%. CONCLUSIONS: MTC was associated with clinical improvement across all DAMs with the greatest change in patients with RA disease activity above the Youden threshold identified in this work. TRIAL REGISTRATION: VARA Registry, https://www.hsrd. RESEARCH: va.gov/research/abstracts.cfm?Project_ID=2141698764.

Assessing the Association of Formulary Copayment Changes with Real-World Treatment Patterns in Patients with Rheumatoid Arthritis on Etanercept.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease that requires long-term treatment to improve or maintain stable disease activity. Tumor necrosis factor inhibitors (TNFi), a class of biologic disease-modifying antirheumatic drugs (bDMARD), are effective at treating symptoms and inhibiting joint progression. Although treatment changes are not recommended in patients with stable disease, health plans have recently enacted formulary changes with higher copayments that could disrupt patient access to TNFis. OBJECTIVE: To assess the association of formulary copayment changes with real-world treatment patterns, treatment effectiveness, and health care costs among bDMARD-naive patients with RA receiving the TNFi etanercept. METHODS: This retrospective observational cohort analysis used the IBM Watson Health MarketScan Commercial Claims and Encounters Database. Adult patients with RA with 6 months of stable etanercept use (no refill gap ≥ 45 days) from January 1, 2013, through December 31, 2015, were selected and the index date was set to the first fill date after the stable-use period. Average etanercept copayment was calculated at the drug-plan level. Copayment change was defined as a monthly increase of at least $40 to account for copayment changes attributable to etanercept wholesale acquisition costs between 2014 and 2015. This amount also corresponded to the 90th percentile of average plan-level changes in etanercept copayments in the database, representing an average change in copayment by a payer. Patients were followed ≥ 12 months before and after the index date to track etanercept treatment changes and ≥ 12 months after a treatment change to track costs after etanercept copayment changes. Etanercept persistence, bDMARD switching, refill gaps, and treatment effectiveness (using a validated effectiveness algorithm) were described for patients with or without copayment change during the 12 months post-index or postchange. We also assessed the mean total of all-cause and RA-related expenditure during the 12-month post-index (or postchange) period. RESULTS: 1,970 stable patients met study inclusion criteria (mean [standard deviation] age: 50.3 [9.5] years; 77.8% female) and were evaluated. Of these, 133 (6.8%) patients had a copayment change ≥$40 during follow-up. Overall, most patients (60.3%) persisted on etanercept for the 12-month follow-up period, while 13.0% switched from etanercept, and 8.1% discontinued (refill gap of ≥ 45 days). Nearly half (48.0%) of all patients were considered effectively treated according to a validated algorithm. Compared with patients without a copayment change, those with a copayment change were more likely to switch biologics (19.5% vs. 12.6%; P = 0.021). Although statistical significance was not reached, patients with a copayment change were less likely to be persistent (54.1% vs. 60.7%; P = 0.135), and less likely to be effectively treated (42.1% vs. 48.4%; P = 0.161) than patients without a copayment change. All-cause and RA-related expenditures at baseline and post-copayment change were similar between patients with and without a copayment change. CONCLUSIONS: Changing formulary copayment of etanercept was associated with higher switching without difference in costs or health care utilization between copayment and no copayment change groups. DISCLOSURES: This study was sponsored by Amgen. Bonafede, Manjelievskaia, and Lopez-Gonzalez are employees of IBM Watson Health, which received funding from Amgen to conduct this study. Oko-osi, Collier, and Stolshek are employees and shareholders of Amgen. Gharaibeh was an employee of Amgen at the time of study execution and manuscript drafting. The authors have no other relationships that present a potential conflict of interest. Data pertaining to this study were presented in a poster at the 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, IL.

Tumour necrosis factor inhibitor exposure and radiographic outcomes in Veterans with rheumatoid arthritis: a longitudinal cohort study.

OBJECTIVES: The aim was to estimate the impact of TNF inhibitor (TNFi) exposure on radiographic disease progression in US Veterans with RA during the first year after initiating therapy. METHODS: This historical longitudinal cohort design used clinical and claims data to evaluate radiographic progression after initiation of TNFi. US Veterans with RA initiating TNFi treatment (index date), ≥ 6 months pre-index and ≥ 12 months post-index VA enrolment/activity, and initial (6 months pre-index to 30 days post-index) and follow-up (10-18 months post-index) bilateral hand radiographs were eligible. The cumulative TNFi exposure and change in modified Sharp score (MSS) between initial and follow-up radiographs were calculated. The percentage of patients with clinically meaningful change in MSS (≥ 5) for each month of exposure was assessed using a longitudinal marginal structural model with inverse probability of treatment weights. Mean values and CIs were generated using 1000 bootstrapped samples. RESULTS: For 246 eligible patients, the mean (s.d.) age was 58 (11) years; 81% were male. The mean (s.d.) initial MSS was 19.6 (33.4) (range 0-214). The mean change (s.d.) in MSS was 0.3 (3.6) (median 0, range -19 to 22). Patients with the greatest exposure had the least radiographic progression for both crude and adjusted model analyses. Adjusted rates of MSS change ≥ 5 points (95% CI) were 10.6% (9.8%, 11.4%) for patients with 3 months of exposure compared with 5.4% (5.1%, 5.7%) for patients with 12 months of exposure. CONCLUSION: One-year changes in radiographic progression were small. Patients with the greatest cumulative TNFi exposure experienced the least progression.

Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting.

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as "existing use" starting before registry entry or "initiated use" starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with < 12 months of follow-up after first use. Among evaluable patients who initiated use of TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with < 12 months of follow-up after first use. After initiation of index therapy, most changes (19-27% of patients) were discontinuation; 4-13% switched biologic therapy during follow-up. The results of this analysis of real-world treatment patterns in a PsA patient registry suggest that nonpersistence for TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy occurs more commonly after initiation of therapy than in patients with existing therapy. Trial registration: NCT02530268.

Therapy with Biologic Agents After Diagnosis of Solid Malignancies: Results from the Corrona Registry.

OBJECTIVE: Guidelines suggest that rheumatoid arthritis (RA) patients with previously treated solid malignancy may be treated as patients without such history. The recommendation is based on limited evidence, and rheumatologists and patients are frequently hesitant to start or continue biologic therapy after a cancer diagnosis. The objective of this study was to describe biologic use in real-world patients with RA following a malignancy diagnosis. METHODS: RA patients enrolled in the Corrona registry and diagnosed with solid malignancy with at least 1 followup visit within 12 months after diagnosis were included in this analysis. The proportion of patients continuing or initiating biological/targeted synthetic disease-modifying antirheumatic drug (bDMARD/tsDMARD) after diagnosis was estimated. Median time to initiation of bDMARD/tsDMARD after diagnosis was calculated using the Kaplan-Meier method and the proportion initiating biologic treatment in 6-month time intervals was estimated using the life-table method. RESULTS: There were 880 patients who met inclusion criteria with 2585 person-years total followup time postdiagnosis. Of those, 367 (41.7%) were treated with bDMARD/tsDMARD within 12 months preceding malignancy, of whom 270 (30.7%) were taking such agents at first postdiagnosis visit. Forty-four (5%) switched biologic agents within 36 months and an additional 90 patients (10.2%) started a biologic. The majority of bDMARD/tsDMARD initiations during followup was a tumor necrosis factor inhibitor (TNFi; 53.5%). CONCLUSION: In real-world practice, nearly one-third of RA patients with a cancer diagnosis were treated with systemic therapy in the immediate visit after malignancy diagnosis and a considerable percentage of malignancy survivors initiated biologic therapy within 3 years. The majority of bDMARD/tsDMARD initiations post-malignancy diagnosis was a TNFi.

Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial.

OBJECTIVE: To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA). METHODS: In this double-blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed. RESULTS: Patients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between-group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen. CONCLUSION: Etanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow-up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept.

Utility of administrative and clinical data to predict major change in medical treatment in US Veterans enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry.

OBJECTIVES: To examine factors associated with major therapeutic changes (MTC) among US Veterans with moderate/severe rheumatoid arthritis (RA) based on Disease Activity Score based on 28 joints (DAS28). METHODS: We used data from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry from 1/1/2006 through 12/31/2014. The index date was a clinic visit with DAS28 >3.2 (moderate/severe disease) following an 18-month pre-index period that included ≥2 DAS28 measurements ≥60 days apart. The patients were followed for MTC from 7 days pre-index through 90 days post-index. Poisson multivariable regression models were used to identify associations with MTC. Chart review of a subset of randomly selected patients explored factors that impacted therapeutic decisions. RESULTS: Among 941 patients, 396 (42.1%) had MTC. Of these, 369 (39.2%) patients had worsening DAS28 at index, 118 (12.5%) had DAS28 improvements, and 454 (48.2%) patients had no change in DAS28 versus pre-index DAS28. Of the patients with worsening DAS28, no change in DAS28, and improved DAS28, respectively, 50.5%, 62.6%, and 70.3% had no MTC. Regression analyses showed index DAS28, oral steroid or non-biologic disease-modifying anti-rheumatic drug (nbDMARD) use in the previous year were associated with an increased likelihood of MTC; use of nbDMARDs in the previous 90 days was associated with a decreased likelihood of MTC. The most common reason for not modifying therapy despite DAS28 >3.2 was a judgement of mild disease. CONCLUSIONS: Clinicians frequently do not institute major therapeutic changes despite DAS28 indicating moderate/severe disease activity; multiple factors are involved in real-world treatment decisions.

Design and rationale of the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA).

OBJECTIVE: To evaluate the efficacy of etanercept and methotrexate as monotherapies and as combination therapy in subjects with active psoriatic arthritis (PsA). METHODS: The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) is an ongoing, global, double-blind, 48-week, randomised, controlled study. Subjects are randomised (1:1:1) to etanercept monotherapy, methotrexate monotherapy or etanercept-methotrexate combination therapy. Endpoints include rates of ACR20 response and Minimal Disease Activity, measures to characterise extra-articular manifestations (dactylitis, enthesitis, nail disease) and safety. CONCLUSION: SEAM-PsA will characterise the effects of etanercept with and without background methotrexate and methotrexate alone on PsA manifestations, and provide information of practical importance to clinicians on the optimal treatment of PsA.