[Show abstract][Hide abstract] ABSTRACT: Objectives:
To determine the baseline factors predictive of significant radiographic progression (SRP) in patients with moderately active rheumatoid arthritis (RA) despite receiving methotrexate (MTX).
Patients from the MTX arm of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) trial with sustained moderate RA (defined as ≥3.2 mean disease activity score in 28 joints ≤5.1 during the last 6 months of the first year) were analysed for SRP (mTSS >3.0 overall) after 2 and 3 years. Baseline predictors for SRP were identified by univariate and multivariate analyses. All variables shown to be significantly associated with SRP were categorised based on clinically relevant cut-offs and tertiles and were included in a matrix risk model.
228 patients were assigned MTX treatment, 210 patients were in the radiographic intention-to-treat population, and 96 of these had sustained moderate RA. SRP occurred in 25 (26%) and 33 (34%) patients after 2 and 3 years of MTX treatment, respectively. Univariate and multivariate analyses found that C reactive protein (CRP) and rheumatoid factor (RF) positivity at baseline were predictive of SRP after 2 and 3 years (p<0.05 for all). The matrix risk model showed that RF positivity and CRP levels >40 mg/L at baseline were significantly associated with SRP after 2 (p<0.05 for both; R(2)=0.24) and 3 years (p<0.05 for both; R(2)=0.22). The baseline erosion score was not found to be predictive of SRP.
Patients with sustained moderate RA despite receiving MTX treatment are at risk of SRP, with both RF positivity and high CRP levels shown to be predictive of this.
[Show abstract][Hide abstract] ABSTRACT: 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).
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).
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.
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.
No preview · Article · Aug 2014 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Background
In clinical practice, patients with psoriasis may require intermittent therapy as part of their long-term treatment programme. Those achieving Physician's Global Assessment (PGA) of ≤ 1 (almost clear/clear) are more likely to be selected as candidates for intermittent therapy than those with a higher PGA (≥ 2; mild or worse), who may relapse sooner or have a delayed response. The objective of this analysis was to determine if patients achieving PGA ≤ 1 using intermittent etanercept (ETN) therapy could regain response (defined as PGA ≤ 2) after relapse.Methods
In the CRYSTEL study (clinicaltrials.gov NCT00195507), patients with moderate-to-severe psoriasis were treated with ETN 50 mg twice weekly (BIW) for ≤ 12 weeks (or for an extra 12 weeks with ETN 25 mg BIW until PGA ≤ 2 was achieved). Patients who reached PGA ≤ 1 during this time were selected for this post hoc analysis (Cycle 1). Treatment was paused, and patients who relapsed (PGA > 2) were retreated with ETN 25 mg BIW until recovery (PGA ≤ 2, Cycle 2). Treatment cycles were continued for up to 54 weeks. The proportion of PGA responders and the time to attain response were calculated, and patient satisfaction was evaluated using the Patient Satisfaction Survey.ResultsDuring Cycle 1, 131 patients achieved PGA ≤ 1 within a median of 9 weeks and subsequently relapsed after treatment cessation. In Cycle 2, 119 (91%) patients attained PGA ≤ 2 within a median time of 7 weeks. The majority of patients were either ‘very satisfied’, ‘satisfied’ or ‘somewhat satisfied’ during both Cycle 1 (100% in total) and Cycle 2 (97% in total).Conclusion
Patients achieving the stringent criteria of PGA ≤ 1 with ETN therapy before ceasing treatment, and subsequently relapsing, were able to quickly regain response during retreatment. The majority of patients considered their therapy to be satisfactory.
No preview · Article · Aug 2014 · Journal of the European Academy of Dermatology and Venereology
[Show abstract][Hide abstract] ABSTRACT: Cyclosporine is an established therapy for psoriasis that provides rapid relief of symptoms but has long-term toxic side effects. The objective of this study was to demonstrate the efficacy of etanercept as replacement therapy for cyclosporine in patients with moderate to severe plaque psoriasis. Patients with plaque psoriasis were given cyclosporine 5 mg/kg/day until achievement of PASI50 at which point cyclosporine was tapered to 0 over 6 weeks. At week 6, patients were randomised (1:1) to receive etanercept (50 mg/week) or placebo for an additional 24 weeks. Patients in the etanercept group (n = 58) experienced a reduction of -1.1 in mean PASI score (p = 0.233 vs. cyclosporine) at week 30; patients in the placebo group (n = 62) had mean PASI increase of 3.7 (p < 0.001 vs. cyclosporine). The incidence of patients reporting any adverse events was not significant between groups (77% etanercept, 74% placebo; p = 0.675). Etanercept demonstrated higher efficacy and good tolerability as replacement therapy for cyclosporine in plaque psoriasis.
Full-text · Article · Mar 2014 · Acta Dermato-Venereologica
[Show abstract][Hide abstract] ABSTRACT: Background The wording and form of the patient global assessment (PGA) question may influence the response and thus whether or not a patient meets the ACR/EULAR criteria for remission.
Objectives To assess the effect of the definition of PGA on the classification of ACR/EULAR remission and minimal diseae activity in RA patients after starting etanercept.
Methods We recently found a low impact of 3 different definitions of PGA on the evaluation of disease activity based on the DAS28 (Disease activity Score) in 108 active RA patients treated with etanercept for 12 weeks. One definition focused on general health over the last 2-3 weeks, one on disease activity over the last 48 hours, and the final definition comprised the result of the RA Impact of Disease questionnaire (RAID), a weighted mean of 7 questions, one on each of the domains pain, function, fatigue, physical and psychological well being, sleep disturbance and coping. All were assessed on 0-10 numerical rating scales. The current analysis focuses on ACR/EULAR remission. We also studied the effects on patients with a DAS28 <2.6. This was previously termed remission but is better defined as minimal disease activity.
Results Overall, depending on the chosen definition the number of patients in remission was between 9 and 12 (i.e., about 10%)for ACR/EULAR remission and about 26-27 patients (25%) for minimal disease activity. The definition of PGA had little impact on the cases classified in the Boolean or SDAI (Simple Disease Activity Index) definition, with 2-3 discrepant cases per comparison, and kappa coefficients ranging between 0.82 and 0.89. Keeping the PGA definition stable, the impact of using the Boolean or SDAI definition was larger: 4-6 discrepant cases, kappa 0.67-0.80. For minimal disease activity, there were 2-3 discrepant cases between PGA definitions (kappa 0.92-0.95).
Conclusions In this dataset the definition of PGA had little impact on the classification of patients in ACR/EULAR remission or in minimal disease activity state.
Disclosure of Interest M. Boers: None Declared, Y. Brault Employee of: Pfizer SAS, France, I. Logeart Employee of: Pfizer SAS, France, M. Dougados Grant/Research support from: Pfizer SAS, France
No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Background In RA, there is increasing interest in “unusual” patient-reported outcomes (PROs), over and above pain, function and fatigue; namely, quality of sleep, well-being and ability to cope . Although these outcomes are important from the patient’s point of view, are they useful as outcome measures and in particular, are they reliable, and responsive, i.e., do they improve when disease improves with treatment?
Objectives To assess the reliability and responsiveness after introduction of etanercept, of different PROs.
Methods Study: open-label 12-week trial of etanercept in RA . PROs of interest: numeric rating scales (NRS) for sleep, physical and emotional well-being, and coping . Comparison outcomes: “standard” PROs, namely, pain NRS, patient global assessment of disease activity (PGA), modified-HAQ (mHAQ) and fatigue NRS. Reliability: assessed between screening and baseline visits by intra-class correlation (ICC). Responsiveness: assessed between baseline and 12 weeks, by standardized response means (SRM). Only patients with at least 1 etanercept injection were analysed.
Results In all, 108 of the 120 screened patients received at least one etanercept injection: mean age, 54 (SD 13) yrs, mean disease duration 8 (SD 7), 75% were women, all were biologic naïve. Disease was active: mean DAS28 5.5 (SD 0.8), mean mHAQ 0.9 (SD 0.5), mean PGA, 6.5 (SD 1.9). At 12 weeks, mean DAS28 was 3.4 (SD 1.2).
Reliability was highest for sleep, and lowest for PGA and pain, whereas responsiveness was highest for pain and PGA, and lowest for mHAQ (Table).
Conclusions NRS assessing sleep, well-being and coping were found to be generally as reliable and as responsive as “usual” PROs in RA. mHAQ showed poor responsiveness possibly due to floor effects. Sleep and coping were the least responsive “unusual” PROs in this trial, indicating these domains of health may be less accessible to biologic treatment. When assessing the patient’s perspective on treatment, it is feasible and valid to measure “unusual” domains of health by NRS.
Disclosure of Interest L. Gossec Consultant for: Abbott, BMS, Pfizer, Roche, UCB, Y. Brault Employee of: Pfizer, I. Logeart Employee of: Pfizer, M. Dougados Consultant for: Abbott, BMS, Pfizer, Roche, UCB
No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Objective: To evaluate the metrologic properties of composite disease activity indices in rheumatoid arthritis (RA), utilizing information derived from clinical, gray-scale (GS), and power Doppler (PD) ultrasound examinations, and to assess the classification of patients according to disease activity using such indices. Methods This ancillary study utilized data from a multicenter, prospective, randomized, parallel-group study conducted in subjects with moderate RA randomized to receive etanercept and methotrexate (ETN + MTX) or usual care (various disease-modifying antirheumatic drugs [DMARDs]). In multimodal indices, the 28 swollen joint count was either supplemented or replaced by clinically nonswollen joints in which the presence of synovitis was detected either by GS and/or PD and was calculated according to the Disease Activity Score in 28 joints (DAS28) or the Simplified Disease Activity Index (SDAI). Reliability, external validity, and discriminative capacity were calculated at baseline/screening by intraclass correlation coefficient, Pearson's correlation, and standardized response mean, respectively. Results: Data from 62 patients (mean ± SD age 53.8 ± 13.2 years, mean ± SD disease duration 8.8 ± 7.7 years, mean ± SD disease activity 4.6 ± 0.5 [DAS28] and 20.9 ± 5.9 [SDAI]) were analyzed, with 32 receiving ETN + MTX and 30 receiving DMARDs. The metrologic properties were at least as good for GS- and/or PD-based indices as for their clinical counterparts. Using GS- and PD-supplemented indices, an additional 67.8% and 32.3% of patients (DAS28-derived and SDAI-derived indices, respectively) could be classified as having high disease activity at the screening visit. Conclusion: Multimodal indices incorporating ultrasound and clinical data had similar metrologic properties to their clinical counterparts; certain indices allowed for a significantly larger number of patients to be classified to either high or moderate disease activity at the screening visit.
[Show abstract][Hide abstract] ABSTRACT: Background Nail psoriasis is common in patients with psoriasis and can seriously affect their quality of life. Current treatments are limited and there is no standard course of therapy.
Objectives To assess the efficacy and safety of etanercept (ETN) on nail psoriasis in patients with moderate-to-severe psoriasis.
Methods Patients with moderate-to-severe plaque psoriasis, who had previously failed at least one form of systemic therapy for nail psoriasis, were randomized to receive open-label ETN 50 mg twice weekly (BIW) for 12 weeks followed by once weekly (QW) for 12 weeks (BIW/QW group) or ETN 50 mg QW for 24 weeks (QW/QW group). The primary endpoint was the mean improvement in the Nail Psoriasis Severity Index (NAPSI; score range 0–8) over 24 weeks in the target fingernail with the most severe abnormalities.
Results Seventy-two patients received one or more doses of ETN (38 BIW/QW; 34 QW/QW) and 69 patients were included in the modified intent-to-treat population. At baseline, mean (standard error) target fingernail NAPSI score was 6·0 (0·3) in the BIW/QW group and 5·8 (0·3) in the QW/QW group. At week 24, mean target fingernail NAPSI score had decreased significantly by −4·3 [95% confidence interval (CI) −4·9 to −3·7; P < 0·0001] in the BIW/QW group and by −4·4 (95% CI −5·0 to −3·7; P < 0·0001) in the QW/QW group. Improvement in NAPSI showed significant correlation with Psoriasis Area and Severity Index improvement. ETN was well tolerated with no unexpected safety findings.
Conclusions Both ETN regimens were effective at treating nail psoriasis in this patient population.
No preview · Article · Sep 2012 · British Journal of Dermatology
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to investigate patients' perceptions of the acceptability of two devices delivering etanercept for rheumatoid arthritis (RA) treatment and to explore whether specific patients' attributes are associated with device preferences. Two similar multicenter, open-label, randomised, parallel-design studies were conducted in a total of 13 European countries. A total of 640 adult patients with RA were randomised to receive etanercept 50 mg once-weekly subcutaneously for 12 weeks in either a pre-filled syringe (PFS) or a pre-filled pen (PFP). Patient satisfaction at week 12 was measured on a 0- to 10-point Likert scale (primary endpoint). The study was powered to demonstrate non-inferiority of a PFP over PFS for the primary endpoint. At week 12, mean patient satisfaction was 8.3 (± 2.4) points in the pen group and 7.2 (± 2.6) points in the syringe group. Non-inferiority and even superiority of the pen over the syringe was demonstrated. In conclusion, this study showed higher patient satisfaction in the group of patients injecting etanercept with a PFP compared with the group of patients using a PFS.
No preview · Article · Sep 2012 · Zeitschrift für Rheumatologie
[Show abstract][Hide abstract] ABSTRACT: The Rheumatoid Arthritis Impact of Disease (RAID) is a patient-reported outcome measure evaluating the impact of rheumatoid arthritis (RA) on patient quality of life. It comprises 7 domains that are evaluated as continuous variables from 0 (best) to 10 (worst). The objective was to define and identify cut-off values for disease activity states as well as improvement scores in order to present results at the individual level (for example, patient in acceptable state, improved patient).
Patients with definite active RA requiring anti-tumour necrosis factor (anti-TNF) therapy were seen at screening, baseline and after 4 and 12 weeks of etanercept therapy. Answers to "Gold standard" questions on improvement (MCII: Minimum Clinically Important Improvement) and an acceptable status (PASS: Patient Acceptable Symptom State) were collected as well as the RAID score and Disease Activity Score 28- erythrocyte sedimentation rate (DAS28-ESR). Cut-offs were defined by different techniques including empirical, measurement error and gold standard anchors. The external validity of these cut-offs was evaluated using the positive likelihood ratio (LR) based on the patient's perspective (for example, patient's global) and on low disease activity status (such as DAS28-ESR).
Ninety-seven (97) of the 108 recruited patients (age: 54 ± 13 years old, female gender: 75%, rheumatoid factor positive: 81%, disease duration: 8 ± 7 years, CRP: 18 ± 30 mg/l, DAS28-ESR: 5.4 ± 0.8) completed the 12 weeks of the study. The different techniques suggested thresholds ranging from 0.2 to 3 (absolute change) and from 6 to 50% (relative change) for defining MCII and thresholds from less than 1 to less than 4.2 for defining PASS. The evaluation of external validity (LR+) showed the highest LR+ was obtained with thresholds of 3 for absolute change; 50% for relative change and less than 2 for an acceptable status.
This study showed that thresholds defined for continuous variables are closely related to the methodological technique, justifying a systematic evaluation of their validity. Our results suggested that a change of at least 3 points (absolute) or 50% (relative) in the RAID score should be used to define a MCII and that a maximal value of 2 defines an acceptable status.
Full-text · Article · May 2012 · Arthritis research & therapy
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the intraobserver reliability, face validity, and discriminant capacity of different global ultrasound (US) scoring systems for measuring synovitis in rheumatoid arthritis (RA).Methods
This study was ancillary to a 52-week, multicenter, prospective, randomized, open-label, parallel-group outpatient study conducted in patients with moderate RA who were randomized to receive either etanercept combined with methotrexate or various disease-modifying antirheumatic drugs. A total of 66 different synovitis scoring systems were constructed and evaluated, including 11 different joint combinations; data derived from clinical findings, gray-scale US, and power Doppler US (PDUS); and both binary counts and semiquantitative scores.ResultsDue to discontinuation of the trial, only 62 patients, a subset of the initially planned number of patients, were included in this study. Reliability was found to be better for gray-scale US and PDUS than for clinical evaluation of synovitis in patients with stable disease between the screening and baseline visits (range for intraclass correlation coefficient 0.6, 0.95 for gray-scale US and 0.56, 0.93 for PDUS versus 0.31, 0.75 for clinical indices). The median (range) difference in the discriminant capacities of clinical indices versus gray-scale US and versus PDUS was 0.25 (−0.64, 0.96) and −0.025 (−0.59, 0.53), respectively, in the period from baseline to 12 weeks. No relevant differences in metrologic properties were observed regarding the number and composition of joints between the different scoring systems. Our findings suggested that a simplified scoring system referring to gray-scale US and PDUS findings might be sufficient.Conclusion
Our findings indicate that gray-scale US and PDUS have better reliability than generally used clinical indices for evaluating synovitis in RA. PDUS has at least as good discriminant capacity as clinical assessment of synovitis for distinguishing between treatment arms.
[Show abstract][Hide abstract] ABSTRACT: Onset of action is considered to be a key characteristic of the treatment of rheumatoid arthritis. The efficacy of TNF blockers is usually evaluated after 2 to 4 weeks of therapy. EULAR-RAID is a valid patient-reported outcome composite index.
To evaluate the onset of action of etanercept in rheumatoid arthritis patients according to the EULAR-RAID score.
An open-label, single-arm (etanercept 50 mg/week), 12-week study was carried out in patients with active rheumatoid arthritis. Patients were asked to fill in the RAID score questionnaire each day for the first 14 days of the study and at the 4-week and 12-week visits. Onset of action was evaluated by considering: a) changes over time of the EULAR-RAID score; b) the percentage of patients achieving an 'acceptable' condition according to the EULAR-RAID score (e.g. a score ≤3.00).
Of the 120 screened patients, 108 (female: 75%), age 54±13 years, disease duration 8±7 years) were enrolled. At baseline, patients had active rheumatoid arthritis (DAS: 5.4±0.8; CRP: 18.±30mg/l). Eleven patients dropped out of the study. A statistically significant decrease in the EULAR-RAID score was observed by day 1 of therapy. Kaplan-Meier estimates of the proportion of patients achieving an acceptable RAID score were 29.8 [% 95% C.I. 23.8-X42.6], 50 % [95% C.I. 41-60.9], 51.9% [95% C.I. 43.8-63.7], 56% [95% C.I. 49.5-69.1, after 1, 2, 4 and 12 weeks of therapy respectively. The median time to achieve an acceptable EULAR-RAID score was 14.5 days.
This open-label study suggests that patients can perceive a clinically relevant improvement by the first week of etanercept therapy.
No preview · Article · Feb 2012 · Clinical and experimental rheumatology
[Show abstract][Hide abstract] ABSTRACT: Patient global assessment (PGA) is one of the 4 items included in the Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis (RA). We studied the influence of the use of 3 different techniques of PGA on the assessment of disease activity.
We evaluated 3 different DAS28 according to the technique of PGA in 108 patients with active RA before and after 12 weeks of etanercept therapy.
The reliability (intraclass coefficient of correlation) between screening and baseline was very high and similar for the 3 DAS28. The percentage of patients in the different states of disease (from remission to higher disease activity) and the sensitivity to change across the 3 DAS28 scales were very similar.
The different techniques of collection of PGA to be included in the DAS calculation yield similar results. However, an accepted, unequivocal technique should be encouraged in order to reduce heterogeneity in scoring DAS among patients with RA.
No preview · Article · Oct 2011 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: There is limited information regarding the acceptability of injection devices for biological agents.
The primary objective of the study was to investigate patients' perceptions on the acceptability of two devices delivering etanercept. The secondary objectives of the study were to explore whether patients' attributes are associated with preferences.
This was a multicentre, open-label, randomized, parallel-design study. Adult patients with psoriasis were randomized to receive etanercept 50 mg twice-weekly subcutaneously for 12 weeks, either as a pre-filled syringe or as a pre-filled pen. The primary outcome was the patient satisfaction at week 12 with the injection device, as measured on a 0-10-point Likert scale. The study was powered to demonstrate non-inferiority of a pen over a syringe for the primary endpoint.
A total of 421 patients were randomized. Mean patient satisfaction at week 12 was 8.9 (±1.9) points in the pen group and 7.6 (±2.6) points in the syringe group. There was a statistically significant advantage for the pen compared with the syringe. Multiple correspondence analysis showed that very satisfied patients were the oldest and had had psoriasis for a longer duration, while less satisfied patients were the most anxious and depressed. PASI 75 response was achieved by 61% of patients in the pen group and 57% in the syringe group at week 12.
This study showed higher patient satisfaction when injecting etanercept with a pen compared with a syringe. Factors associated with lower satisfaction are younger age, anxiety and depression.
No preview · Article · May 2011 · Journal of the European Academy of Dermatology and Venereology