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.

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.

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.

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.

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.

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.

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.

Rebound in Measures of Disease Activity and Symptoms in Corrona Registry Patients with Psoriatic Arthritis Who Discontinue Tumor Necrosis Factor Inhibitor Therapy after Achieving Low Disease Activity.

OBJECTIVE: Rebound may occur in patients with psoriatic arthritis (PsA) who discontinue TNF inhibitor (TNFi) therapy in low disease activity (LDA). METHODS: Using physician and patient reports, we quantified rebound following TNFi discontinuation [defined as Clinical Disease Activity Index (CDAI) score > 10 or TNFi restart] and time to rebound in adults with PsA in LDA (CDAI score ≤ 10) at TNFi discontinuation. RESULTS: Rebound occurred in 73% (69/94) of patients soon after discontinuation (median time to rebound 8.0 mos, 95% CI 6.0-12.0). CONCLUSION: Rebound occurred frequently in patients with PsA after TNFi discontinuation. TNFi discontinuation after achieving LDA should be carefully considered.

Defining and characterizing sustained remission in patients with rheumatoid arthritis.

The objective of this study is to characterize stability and clinical features of patients with rheumatoid arthritis (RA) in sustained remission. Combination therapy with methotrexate and tumor necrosis factor inhibitors (TNFi) has increased remission rates in RA but optimal regimens to maintain remission are unknown. We describe Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis (SEAM-RA) and data from a run-in period of longitudinal observation. Patients in Simplified Disease Activity Index (SDAI) remission (score ≤ 3.3) receiving etanercept and methotrexate were screened and had to maintain remission over 3 run-in visits/24 weeks before randomization to combination therapy or withdrawal of etanercept or methotrexate. Baseline characteristics were examined for predictive factors for maintaining remission. As of November 2016, 141 patients have enrolled; of these, 64 have been randomized, 34 were ineligible after run-in, and 43 are in run-in period; 70% have completed run-in. Enrolled and randomized patients, respectively, had mean (standard deviation [SD]) disease duration 11.0 (8.6) and 12.6 (9.7) years; mean (SD) duration of etanercept use 4.2 (3.8) and 4.9 (4.2) years; mean (SD) methotrexate dose 15.9 (4.8) and 15.5 (4.9) mg/week; and mean (SD) SDAI scores 1.5 (0.9) and 1.4 (0.8). At enrollment, 73% and 63% were in Boolean remission based on 28 joints and 66/68 joints, respectively. No enrollment characteristic predicted successful completion of run-in. Two-thirds of patients considered to be in remission at enrollment sustained remission through 24 weeks. Baseline characteristics of enrolled patients and those who completed run-in were comparable.

Impact of prior biologic use on persistence of treatment in patients with psoriatic arthritis enrolled in the US Corrona registry.

Psoriatic arthritis (PsA) is a chronic condition characterized by a diverse set of symptoms, from swollen joints to nail disease to skin disease. A variety of treatment options are available, including tumor necrosis factor inhibitors (TNFis). Little is known about treatment persistence in patients with PsA who initiate TNFi therapy, with and without prior biologic use. This study assessed persistence in these subgroups of patients with PsA and identified factors associated with persistence. This retrospective study utilized data from the Corrona registry of patients with PsA-with or without prior biologic experience-who initiated TNFi therapy between October 1, 2002, and March 21, 2013. Kaplan-Meier curves estimated median time to nonpersistence (discontinuation or switch to another biologic). Cox proportional hazards models identified factors associated with TNFi nonpersistence. A total of 1241 TNFi initiations were identified: 549 by biologic-naïve and 692 by biologic-experienced patients. Through 4 years of follow-up, more biologic-naïve than biologic-experienced patients remained persistent. Biologic-naïve patients had a greater mean time to nonpersistence compared with biologic-experienced patients: 32 vs 23 months (p = 0.0002). Moderate and high disease activities based on clinical disease activity index and disease duration were associated with persistence in both biologic-naïve and biologic-experienced patients. Additionally, in the biologic-experienced patients, the number of prior medications and skin disease were associated with persistence. The majority of patients with PsA in this study were persistent with their TNFi therapy; biologic-naïve patients had greater persistence compared with biologic-experienced patients. Predictors of persistence differed slightly between biologic-naïve and biologic-experienced patients.

Changes in Treatment Patterns in Patients with Psoriatic Arthritis Initiating Biologic and Nonbiologic Therapy in a Clinical Registry.

OBJECTIVE: Treatment options for psoriatic arthritis (PsA) have increased and improved in the past decade; treatment patterns in PsA remain poorly understood. Understanding current practices would aid in treatment management of patients with PsA. METHODS: This observational study was based on data from the Corrona registry of adult patients with PsA in North America collected between January 1, 2004, and December 31, 2012. Patients were divided among 3 therapy cohorts: tumor necrosis factor inhibitor (TNFi) monotherapy, methotrexate (MTX) monotherapy, and TNFi and MTX combination therapy. Patients were further divided among 3 study periods to understand changes over time: 2004-2006, 2007-2009, and 2010-2012. Data were collected on persistence, discontinuation, restarting, switching, adding/dropping therapy, and dose stretching. RESULTS: This study included 520 patients: 190 TNFi monotherapy, 217 MTX monotherapy, and 113 combination therapy; 110 from 2004 to 2006, 192 from 2007 to 2009, and 218 from 2010 to 2012. Over time, the proportion of patients initiating TNFi monotherapy decreased, while the proportion initiating combination therapy remained constant. The percentage of patients who were persistent decreased over time across all therapy cohorts, but remained higher in TNFi monotherapy than in other cohorts. Duration of persistence decreased over time. Patients initiating MTX monotherapy were more likely than their TNFi counterparts to add therapy. CONCLUSION: Treatment patterns in patients with PsA have changed from 2004 to 2012. Physicians are not more likely to initiate TNFi monotherapy, although clinical evidence supporting its effectiveness has increased over this study period, and patients remain more persistent with it.

The effect of etanercept on traditional metabolic risk factors for cardiovascular disease in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) are at an increased risk of cardiovascular disease (CVD). Treatment with tumor necrosis factor inhibitors improves both joint symptoms associated with RA and also CVD risk. This exploratory analysis of a phase 4 study evaluated changes in metabolic risk factors in patients with RA treated with etanercept. Metabolic analytes were measured at baseline, week 12, and week 24 in patients enrolled in a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etanercept in moderately active RA. Patients received either placebo or etanercept 50 mg every week (QW) for 12 weeks, after which all patients received etanercept 50 mg QW through week 24. Levels of metabolic analytes were assessed in all patients, including patients with diabetes and hyperlipidemia, and described descriptively. A total of 210 patients were randomized, 104 to placebo and 106 to etanercept. There were no significant changes in metabolic risk factors from baseline to week 12 or 24 in all patients. Levels of metabolic analytes were similar in patients with diabetes and hyperlipidemia, with some exceptions; fasting glucose and fasting insulin decreased through week 12, and hemoglobin A1C decreased slightly through week 24 in patients with diabetes. Treatment with etanercept did not adversely affect levels of metabolic risk factors for CVD in patients with RA.

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

INTRODUCTION: The 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. METHODS: Data 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. RESULTS: Of 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. CONCLUSION: Patients 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. FUNDING: This research was funded by Immunex Corp., a fully owned subsidiary of Amgen Inc., and by VA HSR&D Grant SHP 08-172.

Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis.

BACKGROUND: There are no systemic therapies approved in the United States to treat pediatric psoriasis. OBJECTIVE: We sought to evaluate long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. METHODS: This 5-year, open-label extension study enrolled patients aged 4 to 17 years who had participated in a 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections, and rates of 75% and 90% improvement in Psoriasis Area and Severity Index score and clear/almost clear on static physician global assessment. RESULTS: Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 serious AEs; only 1 (cellulitis) was considered treatment-related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement in Psoriasis Area and Severity Index score (∼ 60%-70%) and 90% improvement in Psoriasis Area and Severity Index score (∼ 30%-40%) and static physician global assessment status clear/almost clear (∼ 40%-50%) were maintained through week 264. LIMITATIONS: The number of patients remaining on study at week 264 was small. CONCLUSION: Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.

Risk of Subsequent Infection Among Patients Receiving Tumor Necrosis Factor Inhibitors and Other Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: To describe the incidence of subsequent serious infections in patients who received systemic drug therapy after an initial serious infection. METHODS: Patients with rheumatic conditions (rheumatoid arthritis [RA], psoriatic arthritis, ankylosing spondylitis) or psoriasis who experienced a serious infection between January 1, 2006 and December 31, 2011 were identified in a claims database. Patients were required to be continuously enrolled in the Truven Health Analytics MarketScan Research Database for 12 months prior to and at least 60 days after the date of discharge or the end of intravenous antibiotic therapy for the index serious infection. Subsequent serious infection incidence rates per 100 patient-years with 95% confidence intervals (95% CIs) were calculated for up to 18 months post-index, starting 60 days post-index. Cox proportional hazards models were used to adjust for baseline demographic and clinical characteristics, treatment duration, and changes during followup. RESULTS: Among the 21,699 patients who met the inclusion criteria, the majority (84.3%) had RA. Patients who received tumor necrosis factor (TNF) inhibitor therapy after their index infection had a lower rate of subsequent serious infections (18.1 per 100 patient-years for those treated with a TNF inhibitor alone and 17.3 per 100 patient-years for those treated with a TNF inhibitor plus a nonbiologic disease-modifying antirheumatic drug [DMARD]) compared with those treated with a nonbiologic DMARD alone (21.4 per 100 patient-years). Etanercept, either alone (adjusted hazard ratio [HR] 0.87, 95% CI 0.77-0.99) or in combination with a nonbiologic DMARD (adjusted HR 0.76, 95% CI 0.66-0.88), and infliximab (only in combination with a nonbiologic DMARD) (adjusted HR 0.80, 95% CI 0.67-0.95) were associated with a significantly lower risk of subsequent serious infections compared with a nonbiologic DMARD alone. CONCLUSION: We did not observe an increased risk of subsequent infection in patients who received TNF inhibitor treatment following a serious infection. The risk of a subsequent serious infection was lower in patients treated with both a TNF inhibitor and a nonbiologic DMARD compared with that in patients treated with a nonbiologic DMARD alone.