Reduced risk of infections with the intravenous immunoglobulin, IgPro10, in patients at risk of secondary immunodeficiency-related infections.

Aim: Patients with secondary immunodeficiency (SID) are at increased risk of infections and may be treated with immunoglobulin replacement therapy (IgRT). Despite growing efficacy evidence for IgRT in infection prevention in SID, treatment guidelines are not aligned. Materials & methods: A retrospective database analysis was conducted to assess treatment patterns and infection rates in patients at risk of SID-related infections, with or without IgRT (IgPro10) exposure, to evaluate real-world effectiveness of IgRT in infection prevention. Results: Of 11,448 patients included, 222 received IgPro10. B-cell malignancies and solid organ transplants were the predominant underlying conditions. Despite being sicker at baseline, the IgPro10 cohort demonstrated fewer infections post-index than the non-IgRT cohort. Conclusion: IgPro10 may be an effective option for infection prevention in SID.

Secondary immunodeficiency (SID) occurs when the immune system is weakened by external factors, including certain medical treatments. It can leave a person with an increased risk of potentially serious or even fatal infections, as they no longer have adequate defenses against bacteria. Some patients with this condition require treatment to boost their immune system, including supplementation of their antibodies, known as immunoglobulin replacement therapy (IgRT). In this study, we explored whether: (1) patients with conditions that are at risk of SID and associated infections received IgRT; and (2) whether receiving the IgRT reduced the incidence of infections. We found that patients who had IgRT were much less likely to experience infections than those who did not receive IgRT, suggesting that IgRT may be an effective treatment option for preventing infections in patients with compromised immune systems caused by SID.

The role of C-reactive protein as a predictor of treatment response in patients with ankylosing spondylitis.

OBJECTIVES: To determine whether C-reactive protein (CRP) level is predictive of response to tumor necrosis factor-α blocker treatment in patients with ankylosing spondylitis (AS) and whether there is an optimal CRP range for treatment initiation. METHODS: In this post hoc analysis, data on etanercept-treated patients with AS were pooled from four randomized trials. Week 12 responses (ASAS20, ASAS50, ASDAS-CRP < 1.3, and ASDAS-CRP ∆ ≤ 1.1) were evaluated in relationship to baseline CRP levels (normal, defined as ≤ upper limit of normal [≤ ULN]; elevated, > ULN; high, > ULN and ≤ 3xULN; and very high, > 3xULN), baseline levels of patient-reported outcomes (PROs), and CRP levels at weeks 2, 4, and 8, using univariate and stepwise predictor analyses. In addition, relationships between baseline CRP and other baseline predictors were analyzed using stepwise models of response. RESULTS: Among 867 patients, baseline CRP levels were normal in 371 (43%) patients, high in 299 (34%), and very high in 197 (23%). Very high baseline CRP was a significant predictor for all four week-12 outcomes, compared with normal CRP. Conversely, normal CRP at weeks 2, 4, and 8 was a stronger predictor of week 12 response than elevated CRP. PROs were less consistent predictors of response. In addition, there was a significant association between higher baseline CRP and lower age of disease onset (< 40 years) and between normal CRP and lower disease burden. CONCLUSIONS: In patients with AS, both baseline and post-baseline CRP levels can be predictive of response to treatment at week 12, more consistently than PROs. CLINICAL TRIALS: NCT00421915, NCT00247962, NCT00418548, NCT00356356.

Predictors of remission with etanercept-methotrexate induction therapy and loss of remission with etanercept maintenance, reduction, or withdrawal in moderately active rheumatoid arthritis: results of the PRESERVE trial.

BACKGROUND: The aim was to analyze characteristics that predict remission induction and subsequent loss of remission in patients with moderately active rheumatoid arthritis (RA) who received full-dose combination etanercept plus methotrexate induction therapy followed by reduced-dose etanercept or etanercept withdrawal. METHODS: Patients with Disease Activity Score based on 28-joint count (DAS28) >3.2 and ≤5.1 received open-label etanercept 50 mg once weekly (QW) plus methotrexate for 36 weeks. Those who achieved DAS28 low disease activity by 36 weeks were randomized to double-blind treatment with etanercept 50 mg or 25 mg QW plus methotrexate or placebo plus methotrexate for 52 weeks. All analyses were adjusted for the continuous baseline variables of their respective remission outcomes. RESULTS: Younger age, body mass index (BMI) <30 kg/m2, and lower Health Assessment Questionnaire (HAQ) score at baseline were significant predictors of week-36 remission (P < 0.05) based on DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Baseline DAS28, SDAI, and CDAI were significantly predictive of all three remission endpoints (P < 0.05). For all three treatments, the strongest predictors of loss of DAS28 remission included failure to achieve sustained remission (DAS28 < 2.6 at weeks 12, 20, 28, and 36) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1 month, increase in DAS28/SDAI/CDAI at 1 month, and increase in DAS28/CDAI/SDAI components and patient-reported outcomes (PROs) at 1 month. With the exception of not achieving sustained remission, very similar significant predictors were observed for loss of SDAI and CDAI remission. CONCLUSION: These findings suggest that patients with moderately active RA who are younger and have lower BMI, lower HAQ, and lower disease activity at baseline are most likely to achieve remission when receiving combination etanercept and methotrexate induction therapy. In addition, patients who fail to achieve sustained remission with induction therapy and those with worse disease activity and PROs at early time points after initiating maintenance therapy with a full-dose or reduced-dose etanercept-methotrexate regimen or methotrexate monotherapy are most likely to lose remission across all treatment arms. These findings may help guide clinicians' decision-making as they treat patients to remission and beyond. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00565409 . Registered on 28 November 2007.

Patient Preferences Associated with Therapies for Psoriatic Arthritis: A Conjoint Analysis.

BACKGROUND: As psoriatic arthritis (PsA) treatment choices continue to expand, it is important to consider patient preferences for treatment modalities for PsA. Involving patients in treatment decisions can influence adherence to treatment and outcomes of therapy. OBJECTIVE: To determine patient preferences for medication attributes prescribed for patients with PsA. METHODS: A choice-based conjoint survey was mailed to 2800 randomly selected patients with PsA who were enrolled in Humana Medicare and commercial plans. Patients had been diagnosed with PsA between January 1, 2012, and September 30, 2016. The medication attributes included in the survey were the medication route of administration, frequency of administration, ability to reduce daily joint pain and swelling, likelihood of serious infections, improvement in the patient's ability to perform daily activities, achieving clear or almost clear skin, and cost. Hierarchical Bayesian models were used to score patient preferences after adjusting for demographic and clinical characteristics. The mean attribute importance scores were used to rank patient preferences. RESULTS: A total of 468 patients (258 with a Medicare plan and 210 with a commercial plan) completed the survey. The top 3 medication attributes for patients in Medicare plans were route of administration, cost, and improvement in the ability to perform daily activities. For patients in commercial plans, the top 3 medication attributes were cost, route of administration, and frequency of administration. Within the top 2 attributes for patients in both plans, the oral route of administration and lower cost were most preferred. CONCLUSION: Medication route of administration and cost were the 2 most important considerations for patients diagnosed with PsA who were enrolled in Medicare or commercial plans with Humana. As PsA treatment choices continue to expand, considering patient preferences may improve patient adherence and treatment outcomes and should be considered when making treatment decisions for this patient population.

Clinical and demographic factors associated with change and maintenance of disease severity in a large registry of patients with rheumatoid arthritis.

BACKGROUND: We examined models to predict disease activity transitions from moderate to low or severe and associated factors in patients with rheumatoid arthritis (RA). METHODS: Data from RA patients enrolled in the Corrona registry (October 2001 to August 2014) were analyzed. Clinical Disease Activity Index (CDAI) definitions were used for low (≤10), moderate (>10 and ≤22), and severe (>22) disease activity states. A Markov model for repeated measures allowing for covariate dependence was used to model transitions between three (low, moderate, severe) states and estimate population transition probabilities. Mean sojourn times were calculated to compare length of time in particular states. Logistic regression models were used to examine impacts of covariates (time between visits, chronological year, disease duration, age) on disease states. RESULTS: Data from 29,853 patients (251,375 visits) and a sub-cohort of 9812 patients (46,534 visits) with regular visits (every 3-9 months) were analyzed. The probability of moving from moderate to low or severe disease by next visit was 47% and 18%, respectively. Patients stayed in moderate disease for mean 4.25 months (95% confidence interval: 4.18-4.32). Transition probabilities showed 20% of patients with low disease activity moved to moderate or severe disease within 6 months; >35% of patients with moderate disease remained in moderate disease after 6 months. Results were similar for the regular-visit sub-cohort. Significant interactions with prior disease state were seen with chronological year and disease duration. CONCLUSION: A substantial proportion of patients remain in moderate disease, emphasizing the need for treat-to-target strategies for RA patients.

Evaluation of Real-World Experience with Tofacitinib Compared with Adalimumab, Etanercept, and Abatacept in RA Patients with 1 Previous Biologic DMARD: Data from a U.S. Administrative Claims Database.

BACKGROUND: Real-world data comparing tofacitinib with biologic disease-modifying antirheumatic drugs (bDMARDs) are limited. OBJECTIVE: To compare characteristics, treatment patterns, and costs of patients with rheumatoid arthritis (RA) receiving tofacitinib versus the most common bDMARDs (adalimumab [ADA], etanercept [ETN], and abatacept [ABA]) following a single bDMARD in a U.S. administrative claims database. METHODS: This study was a retrospective cohort analysis of patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM codes 714.0x-714.4x; 714.81) and 1 previous bDMARD filling ≥ 1 tofacitinib or bDMARD claim in the Truven MarketScan Commercial and Medicare Supplemental claims databases (November 1, 2012-October 31, 2014). Monotherapy was defined as absence of conventional synthetic DMARDs within 90 days post-index. Persistence was evaluated using a 60-day gap. Adherence was assessed using proportion of days covered (PDC). RA-related total, pharmacy, and medical costs were evaluated in the 12-month pre- and post-index periods. Treatment patterns and costs were adjusted using linear models including a common set of clinically relevant variables of interest (e.g., previous RA treatments), which were assessed separately using t-tests and chi-squared tests. RESULTS: Overall, 392 patients initiated tofacitinib; 178 patients initiated ADA; 118 patients initiated ETN; and 191 patients initiated ABA. Tofacitinib patients were older versus ADA patients (P = 0.0153) and had a lower proportion of Medicare supplemental patients versus ABA patients (P = 0.0095). Twelve-month pre-index bDMARD use was greater in tofacitinib patients (77.6%) versus bDMARD cohorts (47.6%-59.6%). Tofacitinib patients had greater 12-month pre-index RA-related total costs versus bDMARD cohorts (all P < 0.0001) and greatest index use of monotherapy (P = 0.0080 vs. ABA). A similar (all P > 0.10) proportion of patients were persistent with tofacitinib (42.6%) versus ADA (37.6%), ETN (42.4%), and ABA (43.5%). Mean PDC was 0.55 for tofacitinib versus 0.57 (ADA), 0.59 (ETN), and 0.44 (ABA; P = 0.0003). Adjusted analyses generated similar findings to the unadjusted treatment patterns. Tofacitinib had lower adjusted 12-month post-index mean RA-related total costs ($23,568) versus ADA ($29,278; P < 0.0001), ETN ($26,885; P = 0.0248), and ABA ($30,477; P < 0.0001). CONCLUSIONS: In this study, tofacitinib was more commonly used as monotherapy and yielded at least comparable persistence and adherence with lower adjusted mean RA-related total costs versus ADA, ETN, and ABA. Further analysis is warranted given the greater 12-month pre-index bDMARD use and RA-related costs for tofacitinib versus bDMARDs. DISCLOSURES: This study was sponsored by Pfizer. Harnett, Gerber, Gruben, Koenig, and Chen are employees and shareholders of Pfizer. Some data reported in this manuscript have been previously presented at the Academy of Managed Care Nexus 2015; Orlando, Florida; October 26-29, 2015, and was submitted in abstract form to the European League Against Rheumatism Congress; London, United Kingdom; June 8-11, 2016. All authors were involved in the conception and design of this study. Harnett and Gruben were involved in data collection and analysis. All authors interpreted the data, critically reviewed and revised the manuscript, and read and approved the final manuscript.

Discordance between patient and physician assessments of global disease activity in rheumatoid arthritis and association with work productivity.

BACKGROUND: Discordance between patient and physician ratings of rheumatoid arthritis (RA) severity occurs in clinical practice and correlates with pain scores and measurements of joint disease. However, information is lacking on whether discordance impacts patients' ability to work. We evaluated the discordance between patient and physician ratings of RA disease activity before and after treatment with etanercept and investigated the associations between discordance, clinical outcomes, and work productivity. METHODS: In the PRESERVE clinical trial, patients with moderate RA received open-label etanercept 50 mg once weekly plus methotrexate for 36 weeks. Baseline and week-36 disease characteristics and clinical and work productivity outcomes were categorized according to week-36 concordance category, defined as positive discordance (patient global assessment - physician global assessment ≥2), negative discordance (patient global assessment - physician global assessment ≤ -2), and concordance (absolute difference between the two disease activity assessments = 0 or 1). Correlations between discordance, clinical outcomes, and predictors of discordance were determined. RESULTS: At baseline, 520/762 (68.2 %) patient and physician global assessment scores were concordant, 194 (25.5 %) were positively discordant, and 48 (6.3 %) were negatively discordant. After 36 weeks of therapy, 556/763 (72.9 %) scores were concordant, 189 (24.8 %) were positively discordant, and 18 (2.4 %) were negatively discordant. Patients with week-36 concordance had the best 36-week clinical and patient-reported outcomes, and overall, the greatest improvement between baseline and week 36. Baseline pain, swollen joint count, duration of morning stiffness, fatigue, and patient general health significantly correlated with week-36 discordance, p < 0.0001 to p < 0.05. Additionally, baseline pain, patient general health, and C-reactive protein were predictors of week-36 discordance (odds ratios 1.22, 1.02, and 0.98, respectively). For the employed patients, percent impairment while working and percent overall work impairment were highest (greatest impairment) at baseline and 36 weeks in the group with positive discordance. CONCLUSIONS: The percentage of patients with concordance increased after 36 weeks of treatment with etanercept, with concordant patients demonstrating the greatest improvement in clinical and patient-reported outcomes. Discordance correlated with several measures of disease activity and was associated with decreased work productivity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00565409 . Registered 28/11/2007.

Patient Preferences Regarding Rheumatoid Arthritis Therapies: A Conjoint Analysis.

BACKGROUND: Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. OBJECTIVE: To investigate patient preferences for attributes associated with RA treatments. METHODS: A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21-80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to perform daily tasks; and medication burden. Mean attribute importance scores were calculated after adjusting for patient demographics (eg, age, sex, years since diagnosis) using a hierarchical Bayes model. Patient preferences for each treatment attribute were ranked by the importance score. Part-worth utilities (ie, preference scores) were used to perform a conjoint market simulation. RESULTS: A total of 380 patients (response rate, 27.1%) returned the survey. Their mean age (± standard deviation) was 54.9 (± 9.3) years. Nonrespondents were 2 years younger (mean, 52.9 years; P = .002) but did not differ significantly from respondents in known clinical characteristics. After adjustment for demographic characteristics, mean patients' ranking of treatment attribute importance, in decreasing order, was route of administration, 34.1 (± 15.5); frequency of administration, 16.4 (± 6.8); serious adverse events, 12.0 (± 9.3); cost, 10.1 (± 6.2); medication burden, 9.8 (± 8.2); joint pain reduction, 8.9 (± 3.8); and daily tasks improvement, 8.8 (± 4.7). For the route of administration attribute, the part-worth utility was highest for the oral route. Conjoint simulation results showed that 56.4% of respondents would prefer an oral route of administration. CONCLUSION: Based on this survey completed by 380 patients with RA, commercially insured patients with RA consider the route of administration to be the most important attribute of their RA treatment. In this study, the majority (56.4%) of patients preferred the oral route of administration over other routes. Understanding patient preferences may help to inform provider and payer decisions in treatment selection that may enhance patient adherence to therapy.

Predictors of Clinical Remission under Anti-tumor Necrosis Factor Treatment in Patients with Ankylosing Spondylitis: Pooled Analysis from Large Randomized Clinical Trials.

OBJECTIVE: Investigate the role and relation of disease duration of different factors for achieving clinical remission with anti-tumor necrosis factor (TNF) treatment in patients with active ankylosing spondylitis (AS). METHODS: Data pooled from 4 large (n = 1281) clinical trials were used to compare disease duration subgroups for placebo or sulfasalazine (SSZ) versus etanercept (ETN), which, in turn, were analyzed by age of diagnosis ≤ 40 versus > 40 years, HLA-B27 status, and baseline C-reactive protein (CRP) ≤ upper limit of normal (ULN) versus > ULN using chi-square tests, and ANCOVA. The primary efficacy measure was Assessments of SpondyloArthritis international Society (ASAS) partial remission (PR) after 12 weeks of treatment. Also analyzed were Bath AS Disease Activity Index and Functional Index, AS Disease Activity Scores, and ASAS response rates. RESULTS: Overall, a larger percentage of patients achieved ASAS-PR with ETN versus SSZ or placebo. More patients with ≤ 2-year disease duration treated with ETN experienced partial remission (34%) versus longer disease duration (30%, 27%, and 22% for > 2-5, > 5-10, and > 10 yrs, respectively; all p < 0.05). In the subgroup of patients with both disease duration ≤ 2 years and aged ≤ 40 years at diagnosis, the treatment response was even more pronounced. Similar results were seen in HLA-B27-positive patients in the disease duration ≤ 2-year subgroup. Overall, patients with high CRP at baseline had better treatment responses compared with patients with normal CRP. CONCLUSION: Treatment response under anti-TNF treatment with ETN at 12 weeks was greatest among patients with disease duration ≤ 2 years and even more pronounced in subgroups of patients ≤ 40 years old or HLA-B27-positive at diagnosis.

How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate disease activity compared with the Simplified Disease Activity Index?

OBJECTIVES: Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) is used instead of erythrocyte sedimentation rate (DAS28-ESR) to assess rheumatoid arthritis disease activity; however, values for remission and low disease activity (LDA) for DAS28-CRP have not been validated. American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guidelines suggest remission should be calculated by Simplified Disease Activity Index (SDAI) rather than DAS28-ESR. We examined values of remission and LDA of DAS28-CRP that correspond to the respective cut-off points for DAS28-ESR and SDAI from five clinical trials. METHODS: DAS28-CRP cut-offs that best correspond to DAS28-ESR remission <2.6 and LDA ≤3.2 were obtained by cumulative distribution plots, receiver operating curves and maximum concordance and averaged for each approach, treatment group and study. Level of agreement between DAS28-CRP and DAS28-ESR remission and LDA cut-offs was compared against each other and versus SDAI remission ≤3.3 and LDA ≤11. RESULTS: Percentage of patients who achieved remission and LDA by DAS28-ESR cut-offs was greater for DAS28-CRP versus DAS28-ESR regardless of patient population or treatment group. Discordance between CRP and ESR cut-offs ranged from 4%-26% and 8%-23% for remission and LDA, respectively, and 19%-40% and 6%-11% for DAS28-CRP versus SDAI, respectively. Estimated (range) remission and LDA thresholds were 2.4 (2.2-2.6) and 2.9 (2.6-3.3), 1.9 (1.6-2.2) and 3.1 (3.1-3.3) and 2.2 (1.1-2.9) and 3.6 (3.4-4.0) for DAS28-CRP versus DAS28-ESR, DAS28-CRP versus SDAI and DAS28-ESR versus SDAI, respectively. CONCLUSIONS: DAS28-CRP underestimates disease activity when using cut-off points validated for DAS28-ESR; therefore, DAS28-ESR cut-off values should not be applied to DAS28-CRP. Although DAS28-CRP and DAS28-ESR cut-offs for LDA ≤3.2 correspond to SDAI LDA, neither corresponds well to SDAI remission.

Cardiometabolic profile, clinical features, quality of life and treatment outcomes in patients with moderate-to-severe psoriasis and psoriatic arthritis.

Cardiometabolic, clinical and quality-of-life (QoL) measures were assessed before and after etanercept treatment in patients who had moderate-to-severe plaque psoriasis with and without psoriatic arthritis (PsA) in the PRISTINE trial. Adult patients were randomized to receive etanercept 50 mg once weekly or twice weekly double-blind for 12 weeks; all patients subsequently received etanercept 50 mg once weekly open-label through week 24. Metabolic syndrome was identified in 44 and 41% of patients with and without PsA, elevated blood pressure in 73 and 56% (p<0.05) and diabetes in 21 and 9% (p<0.01), respectively. Significant improvements from baseline in Psoriasis Area Severity Index were observed with etanercept therapy at all time points over 24 weeks (p<0.001) independent of PsA history. At baseline, patients with PsA had worse QoL than patients without PsA. After 24 weeks of etanercept, both groups had significant improvement from baseline in QoL, but the PsA group had greater improvement than that without PsA. Cardiovascular comorbidities were common in psoriasis patients with and without PsA, suggesting that clinicians need to be attentive to cardiometabolic parameters in this population. Worse QoL was demonstrated in PsA versus psoriasis alone. Regardless of patients' PsA status, treatment with etanercept significantly improved skin symptoms and QoL measures.

When to adjust therapy in patients with rheumatoid arthritis after initiation of etanercept plus methotrexate or methotrexate alone: findings from a randomized study (COMET).

OBJECTIVE: The objective of these posthoc analyses was to evaluate short-term clinical outcomes as predictors of poor response after 1 year of treatment with combination etanercept/methotrexate (ETN/MTX) therapy versus MTX monotherapy in patients with early rheumatoid arthritis (RA). METHODS: Participants with moderate to severe RA [28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) ≥ 3.2] of 3-24 months' duration received ETN 50 mg weekly plus MTX or MTX monotherapy for 52 weeks. Regression analyses were performed to evaluate the likelihood of remission (DAS28-ESR < 2.6) after 1 year despite poor clinical short-term treatment effects (e.g., absolute or changes from baseline in DAS28-ESR after 4, 8, 12, 20, and 24 weeks of therapy). RESULTS: The magnitude of disease activity and its improvement and timing influenced remission probability in both treatment groups; remission rate was diminished with higher disease activity levels and lower response levels over time from weeks 4 to 24. The rate of DAS28-ESR remission at 1 year was generally greater with ETN/MTX than with MTX alone at most timepoints from weeks 4 to 24. Despite persistent high disease activity (DAS28-ESR > 5.1) after 4, 8, 12, and 24 weeks of therapy, 35%, 27%, 25%, and 22% of patients, respectively, in the ETN/MTX group achieved DAS28-ESR remission after 1 year of continuous treatment; the respective proportions were 33%, 27%, 8%, and 13% in the MTX group. CONCLUSION: High disease activity and less improvement with treatment over time in the initial 24 weeks of treatment, particularly after 12 weeks, were predictive of a lower remission rate after 1 year.

Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)-refractory nonradiographic axial spondyloarthritis (SpA). METHODS: The study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double-blind study); during the subsequent open-label period, all patients received etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the sacroiliac joints and spine was performed at baseline and week 12. RESULTS: One hundred six patients were randomized to the etanercept group and 109 to the placebo group. Of the 215 patients, the mean ± SD age at baseline was 32.0 ± 7.8 years, 154 (72%) were HLA-B27 positive, and 174 (81%) had MRI-confirmed sacroiliitis. At 12 weeks, the proportion of patients with improvement according to the ASAS40 was significantly higher in the etanercept group than in the placebo group (34 of 105 [32%] versus 17 of 108 [16%]; P = 0.006). Patients who received etanercept exhibited a greater reduction in MRI-based scores for sacroiliac joint inflammation (-46.9% versus -10.9%; P < 0.001) and spinal inflammation (-45.4% versus -33.4%; P = 0.04) compared with placebo-treated patients at week 12. Post hoc analyses suggested a possible association between higher baseline C-reactive protein levels or MRI sacroiliac joint inflammation scores and higher rates of ASAS40 response to etanercept. At week 24, patients in the placebo group who had switched to etanercept at 12 weeks exhibited improvement similar to that observed in patients who had received etanercept for 24 weeks. CONCLUSION: In patients with nonradiographic axial SpA, etanercept treatment was associated with rapid, significant improvement in symptomatic disease activity, function, and systemic and skeletal inflammation over 12 weeks; clinical/functional improvement was sustained over 24 weeks.

Short-term efficacy of etanercept plus methotrexate vs combinations of disease-modifying anti-rheumatic drugs with methotrexate in established rheumatoid arthritis.

OBJECTIVES: The aims of this study were to investigate the short-term benefit of etanercept (ETN) + MTX vs conventional synthetic DMARDs (csDMARDs; HCQ, LEF or SSZ) + MTX in subjects with established RA. The effect of disease duration (≤2 years vs >2 years) and severity (moderate vs severe) on treatment outcomes was also assessed. Methods. Data from Asian and Latin American subjects with inadequate response to MTX were pooled from the APPEAL (ETN 25 mg biweekly + MTX or csDMARD + MTX; NCT00422227) and Latin RA (ETN 50 mg/week + MTX or csDMARD + MTX; NCT00848354) studies. Endpoints included the 28-joint DAS with ESR (DAS28-ESR) low disease activity (LDA; ≤3.2), DAS28 remission (<2.6) and HAQ score ≤0.5. RESULTS: Four hundred seventy-eight subjects received ETN + MTX, 245 subjects received csDMARD + MTX [HCQ + MTX (n = 81), LEF + MTX (n = 69), SSZ + MTX (n = 95)]. At week 16, significantly more subjects receiving ETN + MTX vs subjects on csDMARDs + MTX achieved DAS28-ESR LDA (39% vs 18%, P < 0.001), remission (18% vs 7%, P < 0.001) and HAQ ≤0.5 (48% vs 34%, P < 0.001). For both treatment arms, these endpoints were achieved by a greater proportion of subjects with ≤2 years vs >2 years disease duration and with moderate vs severe disease activity. CONCLUSION: Overall, ETN + MTX was more effective in treating subjects with established RA than csDMARDs + MTX at 16 weeks. More subjects with shorter disease duration and moderate disease activity achieved optimal response regardless of treatment regimen. TRIAL REGISTRATION: clinicaltrials.gov, NCT00422227 and NCT00848354.

Open-label observation of addition of etanercept versus a conventional disease-modifying antirheumatic drug in subjects with active rheumatoid arthritis despite methotrexate therapy in the Latin American region.

BACKGROUND: Previous global studies examined etanercept (ETN) + methotrexate (MTX) for treatment of rheumatoid arthritis (RA), but included few subjects from Latin America. OBJECTIVE: The objective of this study was to compare the safety and efficacy of ETN + MTX versus a standard-of-care disease-modifying antirheumatic drug (DMARD) + MTX in Latin American subjects with moderate to severe active RA despite MTX therapy. METHODS: This open-label, active-comparator study (NCT00848354) randomized subjects 2:1 to ETN 50 mg/wk + MTX or investigator-selected DMARD (sulfasalazine or hydroxychloroquine) + MTX (ETN + MTX, n = 281; DMARD + MTX, n = 142). The primary end point was the proportion achieving American College of Rheumatology (ACR) 50 at week 24. Secondary end points included ACR20/70, disease activity score (DAS) 28 measures, and mean change in modified total Sharp score. Patient-reported outcomes were the Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment: RA (WPAI:RA), and Caregiver Burden and Resource Utilization. Statistical analyses were stratified by country; χ test and analysis of covariance were used. Adverse events were monitored. RESULTS: More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX (62% vs 23%, respectively), in addition to secondary end points (P < 0.0001 for all); mean change in modified total Sharp score was lower for the ETN + MTX group (0.4 vs 1.4, respectively; P = 0.0270). Improvements in patient-reported outcomes favored ETN + MTX for Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale for depression, WPAI:RA, and Caregiver Burden and Resource Utilization emergency department visits for RA (P < 0.01). Overall, adverse events were similar between the groups (69% vs 68%,); serious adverse events were also similar (4% vs 1%). The rate of overall infections was higher with ETN + MTX (38%) than DMARD + MTX (22%, P ≤ 0.001). CONCLUSIONS: Consistent with published global data among RA patients with inadequate response to MTX, adding ETN to MTX demonstrated better efficacy than adding one other conventional DMARD to MTX. No new safety issues were observed. ETN + MTX provided favorable benefit-risk profile among RA patients from LA region.

Cardiometabolic biomarkers in chronic plaque psoriasis before and after etanercept treatment.

OBJECTIVE: To assess cardiometabolic biomarkers in patients with psoriasis before and after etanercept treatment. METHODS: Patients with moderate-to-severe plaque psoriasis were randomized to etanercept 50 mg once or twice weekly, double-blinded. Cardiometabolic biomarkers were assessed at baseline and after 12 weeks of treatment (n = 273). RESULTS: At baseline, 42% of patients had metabolic syndrome. Etanercept was not associated with any clinically relevant adverse effects on cardiometabolic biomarkers. In the once-weekly subgroup, significant mean percentage changes from baseline (p < 0.05) were observed for the quantitative insulin-sensitivity check index (QUICKI; -2.2%), apolipoprotein (Apo) A1 (3.2%), Apo B:Apo A1 ratio (-3.5%), leptin (8.6%) and high-sensitivity C-reactive protein (hsCRP) (-65.5%); and in the twice-weekly subgroup for plasma insulin (15.9%), QUICKI (-2.7%), high-density lipoprotein cholesterol (HDL-C; 2.9%), apolipoprotein (Apo) A1 (2.8%), Apo B:Apo A1 (-4.6%) and hsCRP (-74.4%). CONCLUSION: Metabolic syndrome was common in these patients with moderate-to-severe psoriasis. Etanercept treatment may provide some potentially favorable modulation of insulin sensitivity, HDL-C, Apo A1 and Apo B:Apo A1 ratio.

Utility of the PASE questionnaire, psoriatic arthritis (PsA) prevalence and PsA improvement with anti-TNF therapy: results from the PRISTINE trial.

OBJECTIVE: The authors tested the Psoriatic Arthritis Screening and Evaluation (PASE) to assess usefulness for psoriatic arthritis (PsA) screening before and after anti-TNF treatment in a clinical trial setting. METHODS: Participants of the PRISTINE trial (NCT0066305) were randomized to etanercept 50 mg once weekly or twice weekly. PASE was administered at baseline and 12 weeks of treatment. Scores were compared by a paired sample t-test. Logistic regression and receiver operating curves were used to compare disease assessments against the PASE scores. RESULTS: Participants (N = 273, once weekly, N = 137; twice weekly, N = 136) had a mean age of 44 years; 70% were male; mean PASI was 21. At baseline, 31% had a self-reported history of physician-diagnosed PsA (mean duration, 8 years); ∼25% had a PASE total score ≥47, indicating active PsA. At week 12, 14% had scores ≥47 (p =. 0143). PASE scores correlated with subject global assessment of joint pain. CONCLUSIONS: The PASE was used in a randomized controlled clinical trial in a moderate to severe psoriasis population with a high prevalence of PsA. The findings also support the use of PASE as a tool to measure treatment response for PsA.

Comparison of physician and patient global assessments over time in patients with rheumatoid arthritis: a retrospective analysis from the RADIUS cohort.

BACKGROUND: In rheumatoid arthritis (RA), there is discordance between patient and physician assessments of disease severity and treatment response. OBJECTIVE: This retrospective analysis of the RADIUS (RA Disease-Modifying Anti-Rheumatic Drug Intervention and Utilization Study) 1 cohort examined specific factors that influence differences in global assessments for therapeutic effectiveness of disease-modifying antirheumatic drugs made by physicians (physician global assessment [PhGA]) and patients (patient global assessment [PtGA]). METHODS: The RADIUS 1 cohort consisted of primarily community-based private practice patients with RA requiring either the addition of or a switch to a new biologic or nonbiologic disease-modifying antirheumatic drug and who were followed for up to 5 years by their rheumatologists. Periodic assessments included PhGA, PtGA, Health Assessment Questionnaire-Disability Index (HAQ-DI), 28-item tender/painful joint count (TJC28), swollen joint count (SJC28), pain Visual Analog Scale (VAS), and acute-phase reactants. RESULTS: Among 4359 patients (mean disease duration, 7.3 years), PhGA most highly correlated with TJC28 (0.6956; 95% confidence interval [CI], 0.6881-0.7030) and SJC28 (0.6757; 95% CI, 0.6678-0.6834). Moderate overall correlations were observed for PtGA with TJC28 (0.5000; 95% CI, 0.4890-0.5108) and less 50 with SJC28 (0.3754; 95% CI, 0.3628-0.3878). Patient global assessment most strongly correlated with pain VAS (0.8349; 95% CI, 0.8305-0.8392) and moderately correlated with HAQ-DI (0.5979; 95% CI, 0.5886-0.6071). Acute-phase reactants poorly correlated with PhGA and PtGA. CONCLUSIONS: Low correlations between PhGA and acute-phase reactants suggest that these measurements have a limited contribution compared with the physical examination when physicians make global assessments. These results also suggest that physicians should consider patients' assessments of their disease activity (HAQ, pain VAS, and PtGA) and put joint counts into proper context.