Diederik De Cock

Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial

Objectives To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. Methods 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered. Results Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). Conclusions For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile. EudraCT number: 2008-007225-39.

A detailed analysis of treatment delay from the onset of symptoms in early rheumatoid arthritis patients

Objectives: A treatment delay of more than 12 weeks can negatively affect treatment response in rheumatoid arthritis (RA). Our aim was to quantify the different stages of delay before RA treatment in different rheumatology centres and to explore influencing factors. Method: A total of 156 disease-modifying anti-rheumatic drug (DMARD)-naive early RA patients were included from eight practices: one academic hospital, five general hospitals, and two private practices. Eight different types of delay were defined from symptom onset until treatment initiation. Information on the duration of each stage of delay was collected from the patient, their general practitioner (GP), and patient files at the rheumatology practice. Patient/GP demographics and disease activity/severity parameters were recorded. Results: The median total delay from symptom onset until treatment initiation was 23 weeks whereas patient-, GP- and rheumatologist-related median delay was 10, 4, and 7 weeks, respectively. Only 21.6% of the patients had a total delay of less than 12 weeks. The total median delay in private rheumatology practices was less than in academic and general hospitals (p < 0.001). Furthermore, RA patients treated within 12 weeks of symptom onset showed a higher level of disease activity. The duration of rheumatologist-related delay was inversely correlated with disease activity parameters. Patients with morning stiffness were treated, on average, 3 weeks sooner than those without morning stiffness (p < 0.006). Conclusions: In only one out of five early RA patients was treatment initiated within 12 weeks of symptom onset, as recommended. Patient-related delay contributed most to overall delay. Disease activity and type of rheumatology centre are pivotal determinants of delay.

Factors influencing the prescription of intensive combination treatment strategies for early rheumatoid arthritis

Objectives: Despite the availability and demonstrated effectiveness of intensive combination treatment strategies (ICTS) for early rheumatoid arthritis (RA), a discrepancy seems to exist between theoretical evidence and actual prescription in daily practice. The purpose of this study was to explore and identify the factors influencing the prescription of ICTS. Method: This study involved rheumatologists and nurses participating in the Care for Rheumatoid Arthritis (CareRA) trial, a multicentre randomized controlled trial (RCT) comparing different ICTS for early RA with conventional disease-modifying anti-rheumatic drugs (DMARDs) plus step-down glucocorticoids (GCs). A qualitative study was carried out using individual semi-structured interviews. Each interview was recorded, transcribed literally, and analysed thematically. In addition, observations at outpatient clinics were used to clarify the interpretation of the results. Results: We interviewed 26 rheumatologists and six nurses and observed five outpatient visits. Identified facilitators included available scientific evidence, personal faith in treatment strategy, staff support, and low treatment costs. Rheumatologists had no doubts about the value of methotrexate (MTX) but some questioned the value of combination strategy, others the effectiveness and/or the dosage of individual compounds. Additional barriers for prescribing ICTS included need for patient education, fear for patients’ preconceptions, concerns about applicability to the individual patient, difficulties with breaking routine, interference with organizational structures and processes, time constraints, and lack of financial support. Conclusions: A heterogeneous set of factors highlights the complexity of prescribing ICTS for early RA in daily clinical practice. Future improvement strategies should stimulate the facilitators while at the same time addressing the barriers. The generalizability of these findings to other health care systems needs further examination.

Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial

Objectives Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. Methods The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60 mg), COBRA Slim (MTX + prednisone step-down from 30 mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30 mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639). Results 98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals. Conclusions MTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed. Trial registration numbers EudraCT-number 2008-007225-39 and NCT01172639; Results.

Unraveling Patient-Preferred Health and Treatment Outcomes in Early Rheumatoid Arthritis: A Longitudinal Qualitative Study

To unravel the perspective of patients with rheumatoid arthritis (RA) on preferred health and treatment outcomes at 2 time points during the early stage of their disease and treatment.

The optimal combination therapy for the treatment of early rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition traditionally viewed as a severe destructive disease affecting physical health and global wellbeing. The treatment strategies for RA have changed in the last decades from mainly symptomatic towards a more vigorous and targeted approach. Area covered: Reviewing recent literature enhanced by own expertise and research, a case is made for starting early with an intensive combination treatment with glucocorticoids, followed by a treat to target approach in a tight control setting. Implementation issues that need to be addressed to make optimal use of the ‘window of opportunity’ are highlighted. Expert opinion: There is strong evidence in favor of traditional synthetic disease-modifying anti-rheumatic drugs (DMARDs) combined with a remission induction scheme of glucocorticoids to achieve adequate efficacy in controlling early rheumatoid arthritis with good safety and feasibility in daily clinical practice. Furthermore, the most optimal RA treatment should address not only the physician-oriented clinical disease outcomes but also the patient perspective. There is still a need for working on improving implementation of this approach in daily practice in order to provide optimal treatment benefit to more patients.

Pregnancy outcomes in women with rheumatoid arthritis ever treated with rituximab

Hedva Chiu, Samantha Hollingworth, Mieke Van Driel, Parker Magin and Helen Benham School of Medicine, University of Queensland, Herston, School of Pharmacy, University of Queensland, Brisbane, QLD and Discipline of General Practice, University of Newcastle, Callaghan, NSW, Australia Revised version accepted 16 November 2016 Correspondence to: Helen Benham, School of Medicine, University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4012, Australia. E-mail: h.benham@uq.edu.au

A general practice perspective on early rheumatoid arthritis management: A qualitative study from Flanders

ABSTRACT Background: General practitioners (GPs) may play a crucial role in early recognition, rapid referral and intensive treatment follow-up of patients with rheumatoid arthritis (RA). To improve early RA management, perceived barriers in general practice must be addressed. However, the general practice perspective on early RA management remains understudied. Objective: To explore GPs’ experiences, beliefs and attitudes regarding detection, referral, and intensive treatment for early RA. Methods: In 2014, a qualitative study was conducted by means of individual, in depth, face-to-face interviews of a purposive sample of 13 Flemish GPs. Interviews were audio-recorded, transcribed verbatim and coded using the constant comparative method. Results: GPs applied multiple assessment techniques for early RA detection and regularly prescribed non-steroidal anti-inflammatory drugs if they suspected early RA. However, GPs felt unconfident about their detection skills because early RA symptoms are often unclear, diagnostic tests could provide inconclusive results and the incidence is low in general practice. GPs mentioned various approaches and multiple factors determining their referral decision. Perceived referral barriers included limited availability of rheumatology services and long waiting times. GPs considered intensive treatment initiation to be the expertise of rheumatologists. Reported key barriers to intensive treatment included patients’ resistance and non-adherence, lack of GP involvement and unsatisfactory collaboration with rheumatology services. Conclusion: GPs acknowledge the importance of an early and intensive treatment, but experience various barriers in the management of early RA. GPs should enhance their skills to detect early RA and should actively be involved in early RA care.

Extra-cardiac compression and left ventricular inflow obstruction as a complication of a Sengstaken-Blakemore tube.

A 78-year-old man was admitted for a proximal humerus fracture after an accidental fall. On Day 4 after admission, he developed haematemesis. Oesophagogastroscopy revealed oesophageal varices. Bleeding could be initially controlled by an endoscopic ligature of the varices, but 1h later, recurrent haematemesis was seen. A Sengstaken–Blakemore tube was passed down the oesophagus and the gastric balloon was inflated inside the stomach. A traction of 1 …

OP0180 Remission Induction with Dmard Combinations and Glucocorticoids is not Superior to Remission Induction with MTX Monotherapy and Glucocorticoids: Week 52 Results of the High-Risk Group from the Carera Trial

Background To date, intensive DMARD combination therapy with glucocorticoids (GCs) is the most effective treatment approach for the management of early Rheumatoid Arthritis (eRA). The ideal content of the combination and the dose of GCs are however not yet known. Objectives To compare different intensive combination treatment strategies associated with GCs in eRA patients with a poor prognosis at week (W)52 in the CareRA trial. Methods CareRA is a two year prospective investigator-initiated multicenter RCT rooted in daily practice. DMARD naïve eRA patients were stratified into a high or low-risk group based on classical prognostic markers (presence of erosions, rheumatoid factor, anti-cyclic citrullinated protein and DAS28(CRP). High-risk patients (n=290) were randomized to 1 of 3 treatment strategies. 1) Cobra Classic (n=98): Methotrexate (MTX)+Sulphasalazine+60mg prednisone tapered weekly to 7.5mg daily from W7 2) Cobra Slim (n=98): MTX+30mg prednisone tapered to 5 mg daily from W6 3) Cobra Avant-Garde (n=94):MTX+Leflunomide +30mg prednisone tapered to 5 mg daily from W6 From W28, GCs were tapered in all patients and stopped at W34. A predefined treat to target approach was applied. From W40, we aimed for DMARD monotherapy. Efficacy measures were proportions of DAS28(CRP) remission, good EULAR response, clinically meaningful HAQ response, HAQ=0 (ITT analysis). Radiographic progression was measured via the Sharp Van der Heijde score. Adverse events related to therapy (AEs) were registered. Missing data were imputed by last observation carried forward. Results Remission rates were 64.3%, 60.2% and 62.8% in the Classic, Slim and Avant-Garde group respectively (p=0.837). Also no other efficacy outcomes did not differ between groups. 82% of X-ray images were available at baseline. Radiographic progression was minimal. SvH scores were 1.3±2.1, 1.3±2.5 and 1.0±1.4 at baseline and changed over 52 weeks 0.3±0.5, 0.4±1.1 and 0.3±0.6 in the Classic, Slim and Avant-Garde group respectively (p=0.581). The total numbers of AEs were 182 in 65 Classic patients, 125 in 64 Slim patients and 174 in 72 Avant-Garde patients (p=0.026). Serious AEs were reported in 3 Classic, 2 Slim and 3 Avant-Garde patients. Conclusions High rates of remission were achieved at week 52 with csDMARDs and GCs in all remission induction schemes. Cobra Slim showed comparable efficacy with less adverse events compared to DMARD combinations with moderate or high GC dosages. Disclosure of Interest None declared