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.

Evaluation of Patient-Reported Outcomes With Etanercept in Moderate to Severe Plaque Psoriasis Patients After Therapy With Apremilast.

Background: Patients with moderate-to-severe psoriasis can have symptoms resulting in significant impact on patient-reported outcomes (PROs). The effect of etanercept (ETN) in moderate-to-severe psoriasis patients who previously received apremilast (APR) was studied, including impact on PRO endpoints. Methods: In this multicenter, open-label, single-arm, phase 4 estimation study, patients with moderate-to-severe psoriasis who did not have adequate response to APR in the opinion of the investigator received ETN 50mg subcutaneous (SC) twice weekly for 12 weeks, followed by ETN 50mg SC once weekly for an additional 12 weeks. Analysis was conducted for PROs directly and by the Psoriasis Area and Severity Index (PASI) achievement thresholds. Results: Of the 80 patients enrolled, the Psoriasis Symptom Inventory (PSI; total and individual items) had substantial improvement at weeks 12 and 24. Improvement in PSI total score (percent; mean [SD]) in patients who achieved PASI 50, -75, and -90 at week 12 was 57% (30), 67% (24), and 83% (18), respectively and at week 24 was 56% (40), 68% (29), and 80% (25). DLQI responders by PASI 50, -75, and 90 achievements were 69%, 68%, and 90%, respectively, at week 12 and 68%, 77%, and 82% at week 24. The percent of patients reported being "very satisfied" or "satisfied" with treatment at week 12 was 79%, 81%, and 100%, respectively, and at week 24 was 77%, 86%, and 88%. Conclusion: Patient-reported symptoms are important outcomes to consider in psoriasis management. ETN provided benefits in patients who did not have adequate response with APR, with improvements seen in both psoriasis symptoms and patient impact. Clinical Trial Number: NCT02749370 J Drugs Dermatol. 2020;19(4):378-383. doi:10.36849/JDD.2020.4910.

Biosimilars: Considerations for Payers.

Evaluating biosimilars requires payers to go beyond cost considerations: safety and efficacy, reliability of supply and logistics, and the impact of state laws on substitution and interchangeability must all be deliberated.

Open-Label Study to Evaluate the Efficacy of Etanercept Treatment in Subjects With Moderate to Severe Plaque Psoriasis Who Have Failed Therapy With Apremilast.

INTRODUCTION: Response to etanercept therapy in patients who have failed apremilast therapy has not been well characterized. METHODS: In this multicenter, open-label, single-arm, phase 4, estimation study, subjects with moderate to severe plaque psoriasis received etanercept 50 mg SC twice weekly for 12 weeks, followed by etanercept 50 mg SC once weekly for an additional 12 weeks. Subjects had BSA greater than equal to 10%, PASI greater than equal to 10, and sPGA greater than equal to 3 at screening and baseline; and had failed apremilast-because of either failure to achieve or loss of adequate clinical response, or intolerability to apremilast in the opinion of the investigator. Primary endpoint was PASI 75 at week 12. Secondary endpoints included PASI 75 at week 24, PASI 90 at weeks 12 and 24, and patient-reported outcomes: Psoriasis Symptom Inventory (PSI) score (total and individual items) at baseline and weeks 12 and 24, and over time; DLQI responder analysis (5-point improvement in DLQI from baseline or score of 0) at weeks 12 and 24; and patient assessment of treatment satisfaction at baseline and weeks 12 and 24. RESULTS: Among 80 patients, PASI 75 at weeks 12 and 24 was 41.6% (95% CI, 30.4%-53.4%) and 45.5% (34.1%-57.1%), respectively; PASI 90 was 13.0% (6.4%-22.6%) and 22.1% (13.4%-33.0%), respectively. Mean total PSI score (LOCF) improved from 16.6 (95% CI, 15.1-18.0) at baseline to 8.8 (7.3-10.2) and 9.6 (7.9-11.4) at weeks 12 and 24, respectively; improvements in item PSI scores were similar. The percentage of DLQI responders was 66.2% (95% CI, 54.3%-76.8%) and 57.3% (45.4%-68.7%) at weeks 12 and 24, respectively. The percentage of subjects who were satisfied/very satisfied with their psoriasis treatment improved from 5.0% at baseline to 60.8% and 53.3% at weeks 12 and 24, respectively. During the 24-week study, 23.8% and 2.5% of subjects reported an adverse event and serious adverse event, respectively; there were no new safety signals in this study. DISCUSSION: In patients who have failed apremilast, etanercept may represent an effective therapeutic option. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02749370 J Drugs Dermatol. 2018;17(10):1078-1082.

Impact of osteoporosis on high-cost chronic diseases.

OBJECTIVE: To assess the impact of osteoporosis on health care costs for patients with chronic disease (CD): cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), depression, diabetes mellitus (DM), or two or more of these CDs. METHODS: This retrospective analysis included commercially insured or Medicare Advantage male and female members aged 50 years or older with medical and pharmacy benefits who had evidence of osteoporosis and/or one of the CDs during the identification period (January 1, 2007, to October 31, 2009). Cohorts were defined by the presence or absence of osteoporosis and CD (osteoporosis ONLY, CD ONLY, and CD plus osteoporosis) and, for osteoporosis cohorts, by incident (recent diagnosis) or prevalent osteoporosis (long-standing). Primary outcome was total health care costs during 1-year follow-up. Costs, adjusted for baseline characteristics, were analyzed with a generalized linear model with log link and gamma distribution. RESULTS: Of the 494,160 patients, the majority had evidence of CD with or without osteoporosis: CVD (54%), two or more CDs (24%), DM (8%), depression (4%), COPD (1%); 9% had osteoporosis ONLY. The range of actual mean costs was as follows: CD ONLY, $8,377 (CVD) to $12,801 (two or more CDs); CD plus incident osteoporosis, $15,696 (CVD) to $23,860 (two or more CDs); CD plus prevalent osteoporosis, $10,038 (CVD) to $17,997 (two or more CDs). Compared with CD ONLY, baseline-adjusted costs were 66% (two or more CDs) to 91% (DM) higher for CD plus incident osteoporosis and 13% (CVD) to 23% (depression) higher for CD plus prevalent osteoporosis (P < 0.001). CONCLUSIONS: The burden of osteoporosis in patients with CD is significant, particularly for patients with newly diagnosed osteoporosis.

Perspectives on Treatment Burden for Methotrexate and Tumor Necrosis Factor Inhibitors Among Patients With Psoriatic Arthritis and Rheumatoid Arthritis: A Qualitative Study.

OBJECTIVE: To describe patients' perspectives on the burden associated with methotrexate (MTX) or tumor necrosis factor inhibitor (TNFi) use in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Between May 2019 and March 2020, patients receiving MTX and/or a TNFi for either PsA or RA were randomly sampled from the FORWARD data bank and were invited to participate in semistructured telephone interviews. Interviews explored patients' perspectives on treatment burden and experiences with MTX and TNFi and were conducted until data saturation was achieved. Interviews were recorded, transcribed, and analyzed using a grounded theory approach and NVivo v12.0 software. RESULTS: Overall, 25 patients with PsA and 24 patients with RA participated in the interviews. Participants were predominantly women (mean age: 67 years). Nine major themes related to treatment burden were explored, including treatment side effects and their management, psychological burden, effect on daily functioning and work participation, challenges with accessing and administering therapies, financial difficulties or economic impact, and family planning or breastfeeding. Patients receiving MTX mostly reported side effects as the major burden, while cost and concerns with accessing and administering medication were major challenges reported by TNFi users. Treatment discontinuation due to lack of effectiveness was high for PsA, while discontinuation due to medication cost was high for RA. CONCLUSION: Patients experience a wide range of burden associated with treatments used for PsA and RA. Health care practitioners should consider these challenges when prescribing therapy and strive toward reducing this burden by understanding patients' concerns and needs and involving them in decision making.

Side Effects of Methotrexate and Tumor Necrosis Factor Inhibitors: Differences in Tolerability Among Patients With Psoriatic Arthritis and Rheumatoid Arthritis.

OBJECTIVE: To examine the prevalence of side effects with methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: This retrospective analysis, conducted between January 2000 and January 2019, used data from the FORWARD databank. Adult patients enrolled in the registry with self-reported and physician-confirmed diagnosis of PsA or RA were included if they had completed at least one questionnaire before initiating and within 12 months following initiation of MTX or a TNFi. The primary outcome was to examine the prevalence of side effects with MTX and TNFi within the year following treatment initiation. Multivariate logistic regression analysis was performed to examine the association between PsA and RA and the reporting of their side effects. RESULTS: Overall, 116 patients with PsA and 4247 patients with RA newly initiated MTX, and 124 patients with PsA and 4361 patients with RA newly initiated a TNFi. Patients with PsA were more likely to report MTX-related side effects than those with RA (44.8% vs. 29.4%), whereas similar proportions of patients with PsA and RA reported TNFi-related side effects within the first year (24.2% and 22.8%, respectively). Additionally, patients with PsA initiating MTX were more likely to report nausea, vomiting, abdominal pain, depression, and tinnitus than patients with RA initiating MTX or those with PsA or RA initiating a TNFi. CONCLUSION: Patients with PsA reported more side effects than patients with RA, and this difference was more pronounced in those receiving MTX versus TNFi.

Association of physician specialty with psoriatic arthritis treatment and costs.

OBJECTIVES: To describe current psoriatic arthritis treatment and costs by provider specialty using real-world claims data. STUDY DESIGN: Observational, retrospective cohort study of patients in the IBM MarketScan Commercial and supplemental Medicare databases. METHODS: Eligible patients had newly diagnosed psoriatic arthritis with 12 months of continuous enrollment pre- and post index date for their initial claim. Patients were assigned to 1 of 5 provider specialty cohorts. During the 1-year follow-up period, we collected psoriatic arthritis treatment agent and regimen type and total annual medical and health care costs. We used multivariate regression models to determine the conditional associations of provider specialty with costs. RESULTS: A total of 2132 patients with incident psoriatic arthritis qualified. Most providers were rheumatologists (n = 1365; 64%). Rheumatologists commonly prescribed oral small molecules (methotrexate, 56.3% of prescriptions; sulfasalazine, 8.6%; apremilast, 7.0%) as the index therapy, whereas 23.8% of prescriptions were for tumor necrosis factor inhibitors (adalimumab, 14.2%; etanercept, 7.9%; and infliximab, 1.7%). Compared with other specialists, dermatologists prescribed biologics and other specialty drugs more frequently-adalimumab (32.7%), apremilast (14.3%), etanercept (11.6%), and ustekinumab (8.8%)-and methotrexate less frequently (30.6%). The greatest unadjusted median health care costs were observed among dermatologists ($45,548) compared with rheumatologists ($30,411), primary care physicians ($29,927), rheumatologists/dermatologists ($27,393), and other specialists ($27,774). However, after adjusting for patient-level factors, multivariate regression analyses found that provider specialty was not associated with higher health care costs. CONCLUSIONS: In patients with newly diagnosed psoriatic arthritis, physician specialty was associated with different medication choices but not costs.

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.

Effectiveness and Costs Among Rheumatoid Arthritis Patients Treated with Targeted Immunomodulators Using Real-World U.S. Data.

BACKGROUND: Targeted immunomodulators (TIMs) are used for the treatment of moderate to severe rheumatoid arthritis (RA) and include biologic and nonbiologic medications with different mechanisms of action. Data describing disease activity levels in RA are not directly available in claims databases but can be determined using a claims-based effectiveness algorithm. Rheumatology has benefited from the recent introduction of new drugs, many with new mechanisms of action. We provide an analysis of this broader range of medications. OBJECTIVES: To (a) describe and summarize the effectiveness of available TIMs for the treatment of moderate to severe RA and (b) determine the RA-related health care costs per effectively treated patient, using recent data. METHODS: This was a retrospective analysis using data from the IBM MarketScan Commercial Claims and Encounters Database from July 1, 2012, through December 31, 2016. Index date was the new prescription claim for a TIM (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib). A 6-month pre-index baseline period was used to determine demographic and clinical characteristics. Patients without a TIM claim during the baseline period were considered naive; patients with a TIM claim in the baseline period that was different than the index TIM were assessed as receiving second-line therapy. A claims-based algorithm was used to assess 12-month treatment effectiveness and total RA-related costs. Costs included RA-related pharmacy costs and medical costs. RESULTS: Data from 14,775 patients were analyzed, including patients prescribed abatacept (n = 1,250), adalimumab (n = 4,986), certolizumab pegol (n = 387), etanercept (n = 5,266), golimumab (n = 577), infliximab (n = 969), tocilizumab (n = 451), and tofacitinib (n = 889). Of these, 705 were receiving second-line therapy. TIM effectiveness by first-line and second-line therapy, respectively, were abatacept 27.1%, 18.1%; adalimumab 30.9%, 22.1%; certolizumab pegol 20.9%, 14.3%; etanercept 31.4%, 31.5%; golimumab 32.7%, 22.2%; infliximab 21.9%, 21.3%; tocilizumab 30.9%, 30.6%; and tofacitinib 26.0%, 21.6%. The main reason for failing effectiveness was not achieving an 80% medication possession ratio or being nonadherent. The 1-year total RA-related cost per effectively treated patient for first-line and second-line therapies, respectively, were abatacept $121,835, $174,090; adalimumab $112,708, $154,540; certolizumab pegol $149,946, $236,743; etanercept $102,058, $94,821; golimumab $108,802, $140,651; infliximab $155,123, $185,369; tocilizumab $93,333, $109,351; and tofacitinib $100,306, $130,501. CONCLUSIONS: The effectiveness of TIMs from this real-world experience showed that the range of patients who were effectively treated with first-line therapy was higher for certain tumor necrosis factor inhibitors and tocilizumab. The percentages of effectively treated patients were generally lower in second-line treatment compared with first-line except for etanercept, which had the same percentage between lines of therapy. Etanercept had the lowest RA-related cost per effectively treated patient among tumor necrosis factor inhibitors in first-line use and the lowest RA-related cost per effectively treated patient compared with all second-line treatments. DISCLOSURES: This study was sponsored by Amgen. Amgen employees contributed to study design, analysis of the data, and the decision to publish the results. Maksabedian Hernandez and Stolshek are employees and shareholders of Amgen; Gharaibeh was employed by Amgen at the time of this study. Bonafede was employed by IBM Watson Health, at the time of this study, and McMorrow is employed by IBM Watson Health, which received funding from Amgen to conduct this study. Data from this study were presented at AMCP Nexus, October 22-25, 2018, in Orlando, FL.

The Effect of Dose Escalation on the Cost-Effectiveness of Etanercept and Adalimumab with Methotrexate Among Patients with Moderate to Severe Rheumatoid Arthritis.

BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) occasionally increase their doses of tumor necrosis factor (TNF) inhibitors, especially the monoclonal antibody origin drugs such as adalimumab and infliximab, after inadequate response to the initial dose. Previous studies have evaluated the cost-effectiveness of various sequences of treatment for RA in the United States but have not considered the effect of dose escalation. OBJECTIVE: To assess the cost-effectiveness of etanercept and adalimumab by incorporating the effect of dose escalation in moderate to severe RA patients. METHODS: We adapted the open-source Innovation and Value Initiative - Rheumatoid Arthritis model, version 1.0 to separately simulate the magnitude and time to dose escalation among RA patients taking adalimumab plus methotrexate or etanercept plus methotrexate from a societal perspective and lifetime horizon. An important assumption in the model was that dose escalation would increase treatment costs through its effect on the number of doses but would have no effect on effectiveness. We estimated the dose escalation parameters using the IBM MarketScan Commercial and Medicare Supplemental Databases. We fit competing parametric survival models to model time to dose escalation and used model diagnostics to compare the fit of the competing models. We measured the magnitude of dose escalation as the percentage increase in the number of doses conditional on dose escalation. Finally, we used the parameterized model to simulate treatment sequences beginning with a TNF inhibitor (adalimumab, etanercept) followed by nonbiologic treatment. RESULTS: In baseline models without dose escalation, the incremental cost per quality-adjusted life-year of the etanercept treatment sequence relative to the adalimumab treatment sequence was $85,593. Incorporating dose escalation increased treatment costs for each sequence, but costs increased more with adalimumab, lowering the incremental cost-effectiveness ratio to $9,001. At willingness-to-pay levels of $100,000, the etanercept sequence was more cost-effective compared with the adalimumab sequence, with probability 0.55 and 0.85 in models with and without dose escalation, respectively. CONCLUSIONS: Dose escalation has important effects on cost-effectiveness and should be considered when comparing biologic medications for the treatment of RA. DISCLOSURES: Funding for this study was contributed by Amgen. When this work was conducted, Incerti and Jansen were employees of Precision Health Economics, which received financial support from Amgen. Maksabedian Hernandez, Collier, Gharaibeh, and Stolshek were employees and stockholders of Amgen, and Tkacz and Moore-Schiltz were employees of IBM Watson Health, which received financial support from Amgen. Some of the results of this work were previously presented as a poster at the 2019 AMCP Managed Care & Specialty Pharmacy Annual Meeting, March 25-28, 2019, in San Diego, CA.

Psoriatic arthritis treatment patterns and costs among pharmacologic treatment-naïve patients.

OBJECTIVES: Pharmacologic treatment for psoriatic arthritis (PsA) includes traditional oral small molecules (OSMs), tumor necrosis factor inhibitors (TNFis), and newer oral therapies such as a phosphodiesterase-4 (PDE4) inhibitor and a Janus kinase inhibitor. We aimed to describe treatment patterns and health care costs for treatment-naïve patients with active PsA initiating pharmacologic treatment. STUDY DESIGN: This was an observational, retrospective study. METHODS: We assessed treatment patterns and health care costs from the IBM MarketScan Research databases. We calculated costs during the 12-month follow-up period for inpatient and outpatient medical health care, including outpatient prescription costs. RESULTS: A total of 3491 patients were identified for the study. Incident therapies included OSMs methotrexate (58.3%), sulfasalazine (9.8%), hydroxychloroquine (2.3%), and other OSMs (1.9%); TNFis adalimumab (12.3%), etanercept (8.6%), infliximab (1.9%), and other TNFis (1.4%); and the PDE4 inhibitor apremilast (2.6%). Persistence ranged from 15.2% to 34.6% with OSM monotherapy and from 42.9% to 58.2% with TNFi monotherapy. Percentage of patients with a gap of at least 60 days in therapy ranged from 42.9% to 48.5% with OSMs and from 17.9% to 29.9% with TNFis. Mean first-line unadjusted per-patient per-month total health care costs for OSMs ranged from $1029 to $1456 and mean total health care costs ranged from $19,173 to $25,013. Mean unadjusted per-patient per-month total health care costs for TNFis ranged from $4203 to $7063 and mean total health care costs ranged from $45,635 to $60,933. CONCLUSIONS: Although patients using OSMs had generally lower total health care costs, they also had the highest rates of treatment modifications such as low persistence and medication gaps of at least 60 days.

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.

The longitudinal effect of biologic use on patient outcomes (disease activity, function, and disease severity) within a rheumatoid arthritis registry.

INTRODUCTION: Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. METHOD: Longitudinal data were examined from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry. Linear regression modeled the effect of biologic exposure on changes in disease activity (Disease Activity Score-28 with C-reactive protein [DAS28-CRP]), functional status (modified Health Assessment Questionnaire [mHAQ]), and RA severity (Routine Assessment of Patient Index Data [RAPID3]). Biologic exposure was the ratio of time on a biologic relative to time participating in the BRASS cohort. RESULTS: The analysis included 1395 RA patients, 82.3% female, with 6783 unique study visits from 2003 to 2015. At the patient's first visit, mean (SD) age was 56.3 (14.2) years and mean (SD) duration of RA was 12.7 (11.9) years. Average follow-up duration was 5.59 years (range, 1-13). Over time, DAS28-CRP, mHAQ, and RAPID3 scores decreased as the biologic exposure ratio increased. In repeated measures regression models, increased biologic exposure was significantly associated with decreased DAS28-CRP score (ß = - 0.647; P < 0.001), decreased mHAQ score (ß = - 0.096; P < 0.001), and decreased RAPID3 score (ß = - 0.724; P < 0.001) during follow-up. Methotrexate use at baseline predicted decreased DAS28-CRP, mHAQ, and RAPID3 scores during follow-up. Biologic use at baseline predicted increased DAS28-CRP or mHAQ during follow-up. CONCLUSIONS: Increased biologic exposure is associated with decreased disease activity, function impairment, and RA severity. Future studies should examine whether earlier initiation of biologics improves patient outcomes in RA. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01793103 Key Points • Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. • In this analysis of longitudinal annual population samples of 1395 RA patients in the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry, disease activity, function, and severity scores improved as time on biologic therapy increased. • In repeated measures regression models, time on biologic therapy was a significant predictor of improved outcomes for disease activity, function, and RA severity. • Further studies should examine whether earlier initiation of biologics limits the long-term effect of inflammation on RA outcomes.

Decreased Injection Site Pain Associated with Phosphate-Free Etanercept Formulation in Rheumatoid Arthritis or Psoriatic Arthritis Patients: A Randomized Controlled Trial.

INTRODUCTION: Etanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP associated with administration. METHODS: This phase 3b, multicenter, randomized, double-blind, cross-over study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation (sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events. Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and disease indication as fixed-effect covariates and patient-within-sequence as random effect. RESULTS: A total of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was 23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference - 4 mm; 95% confidence interval: - 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points) had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number and similar between formulations; no new safety signals were observed. CONCLUSIONS: The new phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior formulation, with largest pain reductions observed among patients who reported highest pain with the prior formulation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02986139. FUNDING: Amgen Inc, Thousand Oaks, CA USA.

Feasibility and Utility of the Psoriasis Symptom Inventory (PSI) in Clinical Care Settings: A Study from the International Psoriasis Council.

BACKGROUND: The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome measure designed to assess psoriasis signs and symptoms. OBJECTIVES: The aim was to assess the usefulness of the PSI in enhancing patient care in the clinical setting. METHODS: Eight dermatology clinics in six countries enrolled adults representing the full spectrum of psoriasis severity who regularly received care at the clinic. Patients were administered the eight-item PSI (score range 0-32; higher scores indicate greater severity) while waiting for the physician; the physician conducted a static physician global assessment (sPGA) and estimated psoriasis-affected body surface area (BSA) at the same visit. Physicians completed a brief questionnaire after each patient visit, and were interviewed about the PSI after all patients were seen. RESULTS: The clinics enrolled 278 patients; mean [standard deviation (SD)] psoriasis-affected BSA was 7.6% (11.4). Based on BSA, 47.8% had mild psoriasis, 29.1% had moderate psoriasis, and 23.0% had severe psoriasis. Based on sPGA, 18.7% were clear/almost clear, 67.3% were mild/moderate, and 14.0% were severe/very severe. The mean (SD) PSI total score was 12.2 (8.3). Physicians spent a mean (SD) 4.9 (4.8) min discussing PSI findings with their patients (range 0-20 min). Key benefits of PSI discussions included the following: new information regarding symptom location and severity for physicians; prompting of quality-of-life discussions; better understanding of patient treatment priorities; change in treatment regimens to target specific symptoms or areas; and improvement of patient-physician relationship. CONCLUSIONS: The PSI was useful for treated and untreated patients to enhance patient-physician communication, and influenced treatment decisions.

Cost of biologic treatment persistence or switching in rheumatoid arthritis.

OBJECTIVES: To estimate total costs among patients with rheumatoid arthritis (RA) who persisted on or switched from newly initiated biologic therapy. STUDY DESIGN: A retrospective claims database analysis. METHODS: This analysis included adults in the HealthCore Integrated Research Database with RA who initiated treatment with a biologic for RA (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, or tocilizumab) between January 2009 and November 2014. Total healthcare costs (plan- and patient-paid) were estimated for 1 year post index. Treatment persistence was defined as no discontinuation (ie, no refill gap >45 days) and no biologic switch. RESULTS: Of 7468 patients, 45.2% persisted on the index biologic for at least 1 year without a refill gap and 16.7% switched to another biologic in the first year; other patients discontinued the index biologic (23.2%) or restarted after a refill gap (15.0%). Mean 1-year total healthcare costs per patient were $41,901 (95% CI, $40,855-$42,947) among persistent patients and $44,244 (95% CI, $40,820-$47,668) among switchers. In a multivariable analysis of all patients, switchers had 5% higher postindex costs on average than persistent patients (exp(ß) = 1.05; 95% CI, 1.01-1.08), and etanercept had the lowest postindex costs (exp(ß) ranged from 1.03 to 1.51 for other biologics relative to etanercept). CONCLUSIONS: Patients with RA who switched biologic therapy incurred higher 1-year total postswitch healthcare costs compared with patients who were persistent on the index biologic. Healthcare costs were lowest for patients who started on etanercept, particularly those who persisted on etanercept.

Disease-modifying antirheumatic drug initiation among patients newly diagnosed with rheumatoid arthritis.

OBJECTIVES: To determine the rate of timely disease-modifying antirheumatic drug (DMARD) initiation in patients newly diagnosed with rheumatoid arthritis (RA), as recommended per a quality measure endorsed by the National Quality Forum. STUDY DESIGN: Retrospective analysis of claims data from the Truven Health MarketScan commercial and Medicare claims databases. METHODS: Patients newly diagnosed with RA were identified in the claims databases. Outcomes included rate of nonbiologic or biologic DMARD initiation within 12 months of diagnosis; initiation by year (2009-2012), US state, and prescription drug plan; and time to initiation. Multivariate modeling was performed to identify factors associated with initiation or noninitiation. RESULTS: Of 40,040 newly diagnosed patients, 55.5% initiated RA therapy within 12 months, including 21,154 (52.8%) initiating DMARD therapy and 1051 (2.6%) initiating biologic DMARD therapy. Rates were similar for years 2009 (53.3%), 2010 (55.7%), 2011 (56.3%), and 2012 (56.8%), but they varied widely by US state (range, 33.3%-88.0%) and prescription plan (range, 42.6%-63.5% across 8 largest plans). Mean (SD) time to initiation of any RA therapy was 39 (65) days. Predictors of initiation included point-of-service (odds ratio [OR], 1.18) and consumer-driven/high-deductible (OR, 1.19) plans, comorbid psoriasis (OR, 1.30) or diabetes (OR, 1.17), rheumatoid factor test (OR, 3.02), and diagnosis by a rheumatologist (OR, 3.17). Predictors of noninitiation included female sex (OR, 0.94), preferred provider organization plan (OR, 0.87), higher comorbidity score (OR, 0.94), select comorbidities (OR range, 0.65-0.92), and number of prescriptions for any cause (OR, 0.98). CONCLUSIONS: Only slightly more than half of patients initiated RA therapy within 12 months of diagnosis in this commercially insured population.

Two-year adherence and costs for biologic therapy for rheumatoid arthritis.

OBJECTIVES: To evaluate adherence to newly initiated biologic disease-modifying antirheumatic drugs (bDMARDs) in effectively treated patients with rheumatoid arthritis (RA). STUDY DESIGN: Retrospective cohort study of administrative claims data (IMS PharMetrics Plus) for services incurred from July 1, 2008, to December 31, 2014. METHODS: Data from patients with RA aged 18 to 64 years with continuous enrollment for at least 30 months and initiating abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab were analyzed. Treatment effectiveness was determined using a validated algorithm. Outcomes included adherence rates (proportion of days covered ≥80%) for 1 year and 2 years, year 2 adherence among patients effectively and noneffectively treated in year 1, year 2 adherence predictors, and year 2 costs and cost predictors. RESULTS: Across 10,374 patients, adherence rates were 46% for year 1 and 34% for 2 years; rates were lowest for golimumab and highest for infliximab. In year 1, 3076 (29.7%) patients were considered effectively treated. Year 2 adherence was 59% in effectively treated patients, 32% in patients who failed any effectiveness criteria, and 12% in patients who failed only the adherence criterion. Intravenous bDMARDs, older age, male sex, Northeast region, commercial payer, prior DMARD use, index year 2010 or later, and lower preindex all-cause costs each predicted better adherence. Adjusted year 2 all-cause and RA-related costs were $39,425 and $22,123, respectively, for effectively treated patients and $25,313 and $9250 for noneffectively treated patients. Cost predictors included effective treatment, region, payer, and index year. CONCLUSIONS: Adherence to the first bDMARD was suboptimal even in effectively treated patients, suggesting opportunities to improve adherence in patients with RA initiating biologics.