Early Rheumatoid Arthritis Trial Research Articles

P137 First-line tumour necrosis factor inhibitor (TNFi) treatment is associated with high multi-criteria remission early on compared to treat-to-target in a treatment naïve RA cohort

Abstract Background/Aims In rheumatoid arthritis (RA) disease assessment, SDAI and Boolean remission criteria are known to be more stringent in comparison to DAS28-ESR. Comparing remission rates across multiple assessment indices provides a more comprehensive evaluation of disease control. In an early RA trial cohort, we aimed to investigate stringent and multi-criteria remission (MCR) rates and evaluate their proportional change in response to treatment. Methods The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to first-line etanercept+methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) with escalation to ETN+MTX if not in DAS28-ESR remission at week24. Clinical assessments were completed at baseline, weeks12/24/48 (protocolised phase) up to week96 (standard-of-care). Remission cut-points included: DAS28-ESR ≤2.6, SDAI ≤3.3 and Boolean score for individual components≤1. MCR was defined as patients who were in DAS28-ESR, SDAI and Boolean remission concurrently. Descriptive analyses were undertaken to address the above aims. Results Overall, at week12, 26%(31/120) were in SDAI and 13%(16/120) in Boolean remission. This increased to 41%(49/120) and 23%(28/120) respectively by week48. In the ETN+MTX group at week12, 30%(18/60) were in SDAI and 17%(10/60) in Boolean remission. This increased to 43% (26/60) and 32%(19/60) respectively by week48. Stringent remission rates were lower in MTX-TT compared to ETN+MTX and significantly different for Boolean at week48 (15% vs 32%, odds ratio 2.6, 95% confidence interval 1.1 to 6.5, nominal p < 0.05) (Table 1). Of those in remission by the three different criteria, 36%(14/39) were in MCR at week12, with a greater proportion in ETN+MTX group [42%(10/24) compared to 27%(4/15) in MTX-TT]. MCR remained unchanged up to week48 but improved with treatment by week 96 to 45%(27/60). MCR rates did not converge between the 2 treatment groups at week 96 (ETN+MTX 55%; MTX-TT 38%). Conclusion First-line ETN+MTX is associated with higher rates of stringent remission from week 12 compared to MTX-TT, with improvement gradually over time with both strategies. Significantly higher proportion of patients treated with first line ETN+MTX compared to MTX-TT achieved Boolean and MCR. Early TNFi treatment associates with more complete and better cumulative disease activity profile. Patients not meeting MCR early following treat-to-target approach should be considered for more aggressive treatment strategies. Disclosure R. Shukla: None. D. Plant: None. P. Emery: None. M.H. Buch: None.

Psychosocial Burden Predicts Sustained Remission in Early Rheumatoid Arthritis: Unraveling the Complex Interplay of Well-Being and Disease Activity.

This study investigated how psychosocial aspects of disease affect the probability of achieving sustained remission in early rheumatoid arthritis (RA) and explored the directionality of this relationship. Data were analyzed from the randomized controlled Care in Early RA trial. Sustained remission was defined as a continued Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of <2.6 from weeks 16 to 104. Patients completed the Short Form 36 (SF-36) health survey, Revised Illness Perception Questionnaire (IPQ-R), and the Utrecht Coping List. These psychosocial variables were studied at baseline and at week 16 as predictors of sustained remission with logistic regression. Next, subgroups of patients in remission at week 16 were identified by Latent Profile Analysis based on these psychosocial indicators. Time to first loss of remission was then compared between groups by Cox proportional hazards regression. Finally, directionality of associations between psychosocial indicators and DAS28-CRP was explored with cross-lagged panel models (CLPMs). Sustained DAS28-CRP remission was associated with higher SF-36 scores and less passive coping at baseline and with higher SF-36 scores and more positive IPQ-R outcomes at week 16. Among patients in DAS28-CRP remission at week 16 (n=287), 2 subgroups were identified: a low psychosocial burden group (n=231 of 287) and a high psychosocial burden group (n=56 of 287). The low psychosocial burden group retained remission longer (hazard ratio 0.51 [0.35-0.73]). In the CLPM, temporal relationships between psychosocial well-being and DAS28-CRP were complex, bidirectional, and disease-phase dependent. Suboptimal psychosocial well-being and negative illness perceptions predicted lower probability of sustained remission in an early RA cohort. Illness perceptions appeared to become more clinically relevant with time. Finally, 1 in 5 patients showed worse psychosocial outcomes despite early remission, and these patients tended to lose remission earlier.

P215 In a treatment-naïve, early rheumatoid arthritis cohort, baseline ultrasound power Doppler synovitis and tenosynovitis are highly associated with remission when treated with first line etanercept + methotrexate (MTX) but not MTX alone

Abstract Background/Aims Clinical remission is the treatment target in rheumatoid arthritis (RA). In a treatment-naïve, early RA trial (VEDERA: ‘Very early Etanercept and Methotrexate versus Methotrexate with/without Delayed Etanercept in RA’), we previously reported the presence of ultrasound power Doppler synovitis (PDUS) at diagnosis that improved in the majority with treatment. For this study, we aimed to investigate specifically for an association of baseline PDUS and PD tenosynovitis (PDTS) with subsequent clinical remission (DAS28ESR ≤ 2.6) in VEDERA, also comparing the two treatment groups. Methods The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to either first-line etanercept+methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) regime with escalation to ETN+MTX if not in DAS28ESR remission at week 24. Clinically symptomatic and dominant hand (MCP 1-5, wrist, flexor tendons 1-5 and extensor carpii ulnaris tendon) ultrasound assessments were completed at baseline, weeks 12, 24 and 48. PDUS and PDTS were assessed semi-quantitatively and converted to dichotomous (absent = total score 0, present = total score ≥ 1) for this logistic regression analysis. Results At baseline, 68% (81/120) demonstrated PDUS and 68% also demonstrated PDTS overall. In the MTX-TT group, 63% (38/60) had PDUS and 62% (37/60) had PDTS at baseline. In ETN+MTX group, 72% (43/60) had PDUS and 75% (45/60) had PDTS at baseline. As per randomised trial, there were no differences in baseline demographics, DAS28ESR and HAQ between the groups. Overall, baseline PDUS was associated with week 24 remission and baseline PDTS was associated with week 24 and 48 remission (table 1). Baseline PDUS was particularly associated with week 24 remission in the ETN+MTX group, with a high OR (95% CI) of 6.83(1.2 - 38.91) compared to the MTX-TT group [1.75(0.5 - 6.14)]. Baseline PDTS was also associated with a high OR for week 48 remission in the ETN+MTX group (OR [95% CI] 9.13[1.77 - 47.02]) in contrast to an absence of association in the MTX-TT group. Conclusion Baseline PDUS and PDTS are associated with remission in early RA patients treated with TNF-inhibitor treatment. These measures may be useful to stratify patients early for TNF bDMARD to attain the target of clinical remission in RA. Disclosure R. Shukla: None. R. Hum: Other; R.H holds an Academic Clinical Fellowship funded by the National Institute for Health Research (NIHR) through the Integrated Academic Training (IAT) Programme. P. Ho: None. R.J. Wakefield: None. P. Emery: None. M.H. Buch: None.

P217 Describing the evolution of concordance/discordance between DAS28-ESR and ultrasound power Doppler synovitis in a treatment-naïve early RA cohort

Abstract Background/Aims Discordance between DAS28-ESR and ultrasound (US)-detected power Doppler synovitis (PDUS) can lead to unnecessary DMARD cycling. Using DAS28-ESR and PDUS in an early RA trial cohort, we aimed to identify and describe concordance and discordance at diagnosis and evaluate their proportional change in response to treatment. Methods The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to first-line etanercept + methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) with escalation to ETN+MTX if not in DAS28-ESR remission at week 24. Clinical and US assessments were completed at baseline, weeks 12/24/48. Remission was DAS28-ESR ≤2.6 and active disease was DAS28-ESR &amp;gt;2.6. PDUS presence was defined as total PDUS score ≥ 1. Active concordance was defined as active disease with PDUS while active discordance was defined as active disease without PDUS. Remission concordance was defined as remission without PDUS while remission discordance was defined as remission with PDUS. Descriptive analyses were undertaken to address the above aims. Results At baseline all patients had active disease - 67% (81/120) were concordant and 33% (39/120) were discordant. Baseline DAS28-ESR and individual components were higher in the concordant compared to discordant group. In the active concordant group, from baseline to weeks 24 and 48 respectively, 30% (24/81) and 20% (16/81) persisted, and 26% (22/81) and 38% (31/81) became remission concordant; while 30% (24/81) and 35% (28/81) shifted to active discordance at weeks 24 and 48 respectively and 14% (11/81) and 7% (6/81) became remission discordant. In the active discordant group, from baseline to weeks 24 and 48 respectively, 72% (28/39) and 49% (19/39) persisted and only one and two patients were remission discordant; while 8% (3/39) and 15% (6/39) shifted to active concordance at weeks 24 and 48 respectively and 18% (7/39) and 31% (12/39) became remission concordant. Conclusion Discordance of DAS28 is typically associated with later RA. In this report, a third of patients shifted from active concordance to discordance following DMARD treatment early in the RA pathway. Further study is needed to understand how these patients compare to those that started and persisted with active discordance, and also later discordant RA patients. Disclosure R. Shukla: None. D.A. Selby: None. P. Emery: None. D. Plant: None. M.H. Buch: None.

Treatment response and several patient-reported outcomes are early determinants of future self-efficacy in rheumatoid arthritis

BackgroundSelf-efficacy, or patients’ confidence in their ability to control disease and its consequences, was recently prioritised in EULAR recommendations for inflammatory arthritis self-management strategies. However, it remains unclear which factors influence self-efficacy in early rheumatoid arthritis (RA).MethodsData were analysed from the 2-year RCT Care in early RA (CareRA), which studied remission-induction treatment regimens for early RA. Participants completed the Arthritis Self-Efficacy Scale (ASES), Short-Form 36 (SF-36), Revised Illness Perception Questionnaire (IPQ-R), Utrecht Coping List (UCL), RAQoL and Health Assessment Questionnaire (HAQ). Depending on time to first remission (DAS28-CRP < 2.6) and persistence of remission, treatment response was defined as persistent response, secondary failure, delayed response, late response or non-response. The association between ASES scores and clinical/psychosocial factors was explored with Spearman correlation and multivariate linear mixed models. Baseline predictors of week 104 ASES were identified with exploratory linear regression followed by multiple regression of significant predictors adjusted for DAS28-CRP, HAQ, treatment arm, treatment response, cumulative CRP/SJC28 and demographic/serologic confounders.ResultsAll 379 patients had a recent diagnosis of RA and were DMARD-naïve at study initiation. Most patients were women (69%) and RF/ACPA-positive (66%), and the mean (SD) age was 52 (13) years. For all tested outcome measures, better perceived health correlated with higher self-efficacy. While patient-reported factors (HAQ, SF-36, RAQoL, IPQ-R, pain, fatigue and patient’s global assessment) showed moderate/strong correlations with ASES scores, correlations with physician-reported factors (physician’s global assessment, SJC28), TJC28 and DAS28-CRP were weak.Only more favourable outcomes on patient-reported factors and DAS28-CRP were associated with higher ASES scores at each time point.An earlier, persistent treatment response predicted higher ASES scores at both weeks 52 and 104. Significant baseline predictors of week 104 ASES included HAQ; SF-36 mental component score, vitality, mental health and role emotional; IPQ-R illness coherence, treatment control, emotional representations and consequences; UCL Passive reacting; and the RAQoL.ConclusionsPatient-reported outcomes and treatment response were early determinants of long-term self-efficacy in an early RA trial. These results provide further relevance for the window of opportunity in an early treat-to-target strategy and could help to timely identify patients who might benefit from self-management interventions.Trial registrationEudraCT 2008-007225-39

Two-year cost-effectiveness of different COBRA-like intensive remission induction schemes in early rheumatoid arthritis: a piggyback study on the pragmatic randomised controlled CareRA trial

ObjectivesTo evaluate the cost-effectiveness of treat-to-target strategies among recently diagnosed patients with rheumatoid arthritis (RA) using methotrexate (MTX) and a step-down glucocorticoid (GC) scheme (COBRA Slim) compared with (1) this...

P221 Treatment fidelity in the Gait Rehabilitation in Early Rheumatoid Arthritis Trial (GREAT) feasibility study

Abstract Background Many people with early rheumatoid arthritis (RA) report foot pain and walking disability. Self-reported walking disability two years post-diagnosis is the main predictor of persistent disability. A psychologically informed gait rehabilitation intervention (Great Strides) for early RA was developed to address this, consisting of two compulsory sessions and up to four optional sessions delivered over three months. Physiotherapists and podiatrists received bespoke training to deliver Great Strides, incorporating motivational interviewing (MI) and behaviour change techniques (BCTs), to help patients to complete their walking exercises at home. The aim of this study was to assess fidelity of delivery within the Gait Rehabilitation in Early Arthritis Trial (GREAT) feasibility study. Methods Four physiotherapists and two podiatrists delivered 78 Great Strides sessions across three centres in the UK. All sessions were audio recorded and double coded. The Motivational Interviewing Treatment Integrity (MITI) Rating Scale (scoring ≥4 represents good proficiency) and tailored treatment fidelity measures of the six core elements and 17 BCTs delivered in session 1, five core elements delivered in session 2, and 12 BCTs in session 2-6, were developed to examine fidelity of delivery. Two trained, independent assessors rated audio recordings of Great Strides and assessed the extent to which core elements, aspects of MI and BCTs were delivered across sessions. Results Data from 28 (80%) adult participants across a total of 64 sessions were rated for core components and BCTs and 37 (50%) of sessions were analysed for MI. Relational (score=4.4) and technical (score=4.2) aspects of MI were delivered with good fidelity across the whole sample. The 6 core elements and 7 BCTs in Session 1 were conveyed with high (over 80%) treatment fidelity, but 10 further BCTs were not consistently delivered (range 23-69%). In session 2, the 5 core elements and 3 BCTs were provided with high fidelity, but another 9 BCTs were not reliably delivered (range 11-56%). Sessions 3 and 4 reliably delivered 3 out of 12 BCTs and only one session 5 and 6 was delivered. Inter-rater reliability showed agreement of over 80% was reached between raters for all sessions (range 82-87%). Conclusion Physiotherapists and podiatrists were able to deliver the core elements of GREAT sessions with high fidelity and fidelity assessment methods were appropriate. Results showed a maximum of 4 sessions was sufficient. However, treatment fidelity might be enhanced with further training or greater on-going support, as findings suggested clinicians (physiotherapists) with previous MI experience were more proficient at offering key elements of MI. Additionally, the Great Strides intervention could be amended to improve delivery, as research shows complex interventions should consider mandatory BCTs alongside optional ones, depending on the needs of individual participants. Disclosures E. Godfrey None. M. Sekhon None. G. Hendry None. N.E. Foster None. S. Hider None. M. van der Leeden None. H. Mason None. A. McConnachie None. I. McInnes None. A. Patience None. C. Sackley None. M. Steultjens None. A. Williams None. J. Woodburn None. L. Bearne None.

One in five patients with rapidly and persistently controlled early rheumatoid arthritis report poor well-being after 1 year of treatment

ObjectivesTo identify and characterise a subgroup of patients with early rheumatoid arthritis (RA) reporting not feeling well 1 year after treatment initiation despite achieving optimal disease control according to current...

Patient-Reported Outcome Data From an Early Rheumatoid Arthritis Trial: Opportunities for Broadening the Scope of Treating to Target.

Treating early, intensively, and to target leads to rapid disease control, preventing joint damage and loss of function in early rheumatoid arthritis (RA). We report the effect of such an approach on patient-reported outcomes and explore the contribution of rapid and persistent disease control to well-being after 1 year of treatment. This study is part of the Care in Early RA trial, a prospective, 2-year, investigator-initiated, randomized controlled trial rooted in daily practice and implementing the treat-to-target principle. Short Form 36 (SF-36) health survey and Revised Illness Perception Questionnaire (IPQ-R) data were collected prospectively. We defined 4 clinical response profiles based on speed and consistency of the treatment response within the first year, defined as the Disease Activity Score in 28 joints using the C-reactive protein level <2.6. Linear regression analyses including these response profiles and treatment type were constructed to predict the SF-36 dimensions of vitality, social functioning, role emotional, and mental health, and the IPQ-R illness perception subscales of consequences, treatment control, and illness coherence at year 1. A total of 333 patients were available for the main analyses, including 140 early persistent responders. Variation in each of the psychosocial outcomes at year 1 was explained mostly by baseline values, followed by the clinical response profiles. Patients with an early persistent response reported significantly higher vitality, more positive beliefs about disease consequences and treatment effect. Treatment type did not matter. Rapid and persistent disease control and not treatment type were associated with favorable patient-reported health and illness perceptions at year 1, but baseline psychosocial variables mattered most. Our data indicate opportunities to broaden the scope of the treat-to-target principle in early RA.

Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials

BackgroundThe ACR20 has been validated as the best discriminator of efficacy in placebo-controlled trials, but not in head-to-head trials comparing effective therapies in patients with rheumatoid arthritis (RA). We assessed the most discriminatory ACR response and most discriminatory percent improvement in disease activity measures for Simplified Disease Activity index (SDAI), Clinical Disease Activity index (CDAI), and 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) using different patient populations and trial designs.MethodsData from two placebo-controlled studies in established RA and two head-to-head studies in early RA were analyzed. The numeric ACR response for each treatment and P value for the difference between treatments were calculated at multiple time points to determine the ACR response associated with the lowest P value. Similarly, values for percent improvement from baseline in SDAI, CDAI, and DAS28(CRP) with the most discrimination between treatments were examined.ResultsIn the head-to-head early RA trials, the minimum P value and greatest treatment difference between the active comparator arms at 6 months was achieved at higher ACR rates and greater percent improvements in other disease activity measures. In established RA, lower responses (minimum P value and maximum treatment difference) and smaller improvements in disease activity scores had better discriminatory ability at 6 months.ConclusionsThe most discriminatory ACR response rate and percent improvement in disease activity measures were higher in head-to-head active comparator trials in early RA versus placebo-controlled trials in established RA. This difference should be considered in future clinical trial designs.Trial registrationNCT00195663, NCT00420927, NCT00195702.

Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up

ObjectivesMortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample...

Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial

ObjectivesThe aim of this paper was to analyse the impact of obesity, in addition to known predictors, on disease outcome in early rheumatoid arthritis (RA).MethodsBody mass index (BMI) was available...

Long-term outcome is better when a methotrexate-based treatment strategy is combined with 10 mg prednisone daily: follow-up after the second Computer-Assisted Management in Early Rheumatoid Arthritis trial

ObjectivesIn the second Computer-Assisted Management in Early Rheumatoid Arthritis trial, patients had started with methotrexate and 10 mg prednisone (MTX+pred) or placebo (MTX+plac). After the trial, prednisone was tapered and...

Age affects joint space narrowing in patients with early active rheumatoid arthritis

BackgroundJoint space narrowing (JSN) in rheumatoid arthritis (RA) may be a manifestation of (primary) osteoarthritis becoming more prominent with age. We investigated the severity and predictors of JSN progression among...

089 Co-Morbidities after Daily Concomitant Treatment with 10 Mg Prednisone or Placebo in the 2 Year Computer-Assisted Management in Early Rheumatoid Arthritis Trial II

089 Co-Morbidities after Daily Concomitant Treatment with 10 Mg Prednisone or Placebo in the 2 Year Computer-Assisted Management in Early Rheumatoid Arthritis Trial II

FRI0029 The Impact of Very Early Treatment on Patient Reported Outcomes in Rheumatoid Arthritis

BackgroundDespite substantial advances in the treatment of rheumatoid arthritis (RA), patients continue to report long term limitations. The combination of TNFα antagonists and methotrexate (MTX) in early RA (ERA), defined...

Assessment of combination therapy responses in early rheumatoid arthritis defined by presence or absence of anti-citrullinated protein antibodies

BackgroundUK guidelines recommend that all patients with early active rheumatoid arthritis are offered combination disease-modifying anti-rheumatic drugs (DMARDs) and short-term corticosteroids. This heterogeneous disease has several subsets; one crucial subdivision is defined by the presence or absence of anti-citrullinated protein antibodies (ACPA). These subsets may differ in their treatment responses. We used data from a published randomised controlled trial to assess whether responses to intensive combination treatments in early rheumatoid arthritis differ by ACPA status. MethodsThe Combination Anti-Rheumatic Drugs in Early Rheumatoid Arthritis trial randomised 467 patients with early active disease to receive: methotrexate, methotrexate plus ciclosporin, methotrexate plus prednisolone, or methotrexate plus ciclosporin plus prednisolone in a factorial-design. Patients were assessed 6-monthly for 2 years. In this secondary analysis we assessed 431 patients with available ACPA status. To minimise multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline to 2 years for each outcome (Larsen score, disease activity score in 28 joints [DAS28], health assessment questionnaire, EuroQol, and physical component and mental component summary scores). When a significant interaction was present, mean changes in outcomes were compared between treatment groups at each time-point using t tests stratified by ACPA status. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA. FindingsOf the 431 rheumatoid arthritis cases, 310 (72%) were ACPA-positive and 121 (28%) were ACPA-negative. Effect of treatment on radiological progression differed according to ACPA status, with a significant interactive effect between ACPA and treatment on Larsen score changes observed (p<0·001, ANOVA). ACPA-positive patients had significant reductions in Larsen score progression with all treatments; no effect was seen in ACPA-negative disease. ACPA-positive patients receiving triple therapy had the greatest benefits compared with those on monotherapy (2-year mean Larsen score increase 3·66 [95% CI 2·27–5·05] vs 9·58 [6·76—12·39]; OR for new erosions 0·32 [0·14–0·72], p=0·003). ACPA-negative patients had negligible radiological progression irrespective of treatment (2-year mean Larsen score increase 1·70 [0·29–3·10] with triple therapy vs 2·72 [1·15–4·29] with monotherapy; 7% developed new erosions). The beneficial effects of high-dose corticosteroids on reducing disease activity and improving physical health were confined to ACPA-positive disease. InterpretationIn our study, combination DMARDs and corticosteroids provided radiological, disease activity, and physical health benefits only to patients with ACPA-positive early rheumatoid arthritis. These findings suggest that ACPA is an important biomarker for guiding treatment decisions in rheumatoid arthritis. They indicate that current guidelines advocating combination DMARDs and corticosteroids in all patients with early active disease might require reconsideration. FundingArthritis Research UK, National Institute for Health Research, NIHR Biomedical Research Centre.

FRI0445 The performance of matrix-based risk models for rapid radiographic progression in an observational cohort of established rheumatoid arthritis patients

BackgroundMatrix-based clinical risk prediction models have been proposed as a tool to predict rapid radiographic progression (RRP, defined as 5 or more units change in Sharp score/year) in rheumatoid arthritis...

Changes in Lipoproteins Associated With Methotrexate Therapy or Combination Therapy in Early Rheumatoid Arthritis: Results From the Treatment of Early Rheumatoid Arthritis Trial

ObjectiveTo study changes in lipid profiles at 24 weeks among patients with early rheumatoid arthritis (RA) participating in the Treatment of Early RA (TEAR) trial and randomized to receive methotrexate (MTX) plus etanercept, triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or aggressively titrated MTX monotherapy.MethodsThis TEAR substudy included 459 participants with biologic specimens. Serum levels of total cholesterol, low‐density lipoprotein (LDL) cholesterol, and high‐density lipoprotein (HDL) cholesterol were measured at 0 and 24 weeks.ResultsAt 24 weeks, there were statistically significant increases in mean cholesterol levels in the MTX plus etanercept, triple therapy, and MTX monotherapy arms. The observed increases were 31.4 mg/dl, 28.7 mg/dl, and 30 mg/dl in LDL cholesterol, 19.3 mg/dl, 22.3 mg/dl, and 20.6 mg/dl in HDL cholesterol, and 56.8 mg/dl, 53 mg/dl, and 57.3 mg/dl in total cholesterol (P &lt; 0.0001 versus baseline for each comparison). There was a statistically significant decrease in the ratio of total cholesterol to HDL cholesterol at 24 weeks in all 3 treatment groups versus baseline. There was no difference in any lipid changes between the 3 treatment arms. After multivariable adjustment, change in C‐reactive protein, but not the Disease Activity Score in 28 joints, was associated with change in LDL cholesterol (P = 0.03) and total cholesterol (P = 0.01). Baseline glucocorticoid use was associated with changes in HDL cholesterol (P = 0.03) and total cholesterol (P = 0.02).ConclusionLevels of total cholesterol, LDL cholesterol, and HDL cholesterol increased comparably shortly after initiation of MTX plus etanercept, triple therapy, and MTX monotherapy among patients with early RA with active disease participating in a clinical trial. The clinical relevance of short‐term changes in traditional lipids on cardiovascular outcomes remains to be determined.

Timing the therapeutic window of opportunity in early rheumatoid arthritis: proposal for definitions of disease duration in clinical trials

The effects of treatment in early rheumatoid arthritis (RA) and the consequences of delayed therapy represent important areas for research. The concept of a ‘window of opportunity’ is now well...