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.

OBJECTIVE: 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. METHODS: In a longitudinal, qualitative, explorative study, we individually interviewed 26 patients with early RA (ERA) 4-6 months after the start of initial RA treatment. Fourteen of these participants took part in 1 of 3 focus groups at least 1 year after treatment initiation. Interviews were audiotaped, transcribed verbatim, and analyzed using the constant comparison method. Two patient researchers completed the interdisciplinary research team. RESULTS: Patients with ERA ultimately strive to be normal again, literally and figuratively. Outcome preferences inherent to this urge for normality were related to aspects of disease control, physical aspects, aspects of participation, and mental aspects. Initially, patient outcome preferences in ERA were primarily related to pain relief, medication side effects and burden, and emotional well-being. Patient-preferred outcomes evolved over the ERA disease course, with subtle changes in terminology used by participants and with pain relief staying in the foreground. CONCLUSION: From a patient perspective, normality is the ultimate outcome to target in ERA. Our study produced knowledge for designing more targeted therapeutic interventions aimed at normalizing patients' health and life in all its aspects during a crucial phase of RA.

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

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.

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.

Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial.

INTRODUCTION: Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial. METHODS: Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks. RESULTS: We analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ. CONCLUSION: In patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks. TRIAL REGISTRATION: EU Clinical Trials Register Identifier: EudraCT number 2008-007225-39 . Registered 5 November 2008.

A maximum difference scaling survey of barriers to intensive combination treatment strategies with glucocorticoids in early rheumatoid arthritis.

The objectives of the study were to determine the relative importance of barriers related to the provision of intensive combination treatment strategies with glucocorticoids (ICTS-GCs) in early rheumatoid arthritis (ERA) from the rheumatologists' perspective and to explore the relation between rheumatologists' characteristics and importance scores. A maximum difference scaling (MDS) survey was administered to 66 rheumatologists in Flanders and the Brussels-Capital Region. The survey included 25 barriers, previously being discovered in a qualitative study. The survey included 25 choice sets, each of which contained a different set of four barriers. In each choice situation, respondents were asked to choose the most important barrier. The mean relative importance score (RIS) for each barrier was calculated using hierarchical Bayes modeling. The potential relation between rheumatologists' characteristics and the RIS was examined using Spearman's correlation coefficient, Mann-Whitney U test, and Kruskal-Wallis H test. The three highest ranked barriers included "contraindicated for some patients (e.g., patients with comorbidities, older patients)," "an increased risk of side effects and related complications," and "patients' resistance" with a mean ± SD RIS of 9.76 ± 0.82, 8.50 ± 1.17, and 7.45 ± 1.22, respectively. Comparing the RISs based on rheumatologists' characteristics, a different ranking was found for three barriers depending on the age, university location, and/or frequency of prescribing ICTS-GCs. The dominant barriers hindering ICTS-GCs prescription from a rheumatologists' perspective are patient-related barriers and barriers related to the complexity of prescribing a combination therapy including GCs. A tailored improvement intervention is needed to overcome these barriers and should focus on the familiarity of rheumatologists with ICTS-GC and patient education.

Patient experiences with intensive combination-treatment strategies with glucocorticoids for early rheumatoid arthritis.

OBJECTIVES: To investigate patients' experiences with intensive combination-treatment strategies with glucocorticoids (ICTS-GCs) in the early phase of early rheumatoid arthritis (ERA) treatment. METHODS: We interviewed 26 participants individually, 4-6 months after initiation of ICTS-GCs (t1). Fourteen participants from the same sample took part in one of three focus groups at least 1 year after treatment initiation (t2). Each interview was audio-recorded, literally transcribed and thematically coded. RESULTS: The participants described concerns and feelings about ICTS-GCs that changed over time; for example, a fear of side effects diminished when the treatment effects were beneficial or expected side effects did not materialize. Moreover, participants indicated additional information needs at t1 and t2. The most used sources of information were healthcare professionals, relatives, and the Internet. Furthermore, participants reported on their relationship with healthcare professionals and the need for trust and reassurance, especially at t1. Lastly, participants described their personal self-management strategies. CONCLUSION: Despite their concerns at treatment initiation, most participants had positive experiences with ICTS-GCs. PRACTICE IMPLICATIONS: Healthcare professionals should be aware that, in the early phase of treatment, they can address patients' concerns, they are the most important information source, they need to create a relationship of trust, and guide patients in self-management strategies.

How do patients with uncontrolled diabetes in the Brussels-Capital Region seek and use information sources for their diet?

OBJECTIVE: The aim of this study was to obtain qualitative data to understand how type 2 diabetic patients with unregulated blood glucose levels (HbA1c >140 mg/dL) seek and use information sources for their diet. METHODS: A descriptive, explorative study design was used with focus group interviews in the Brussels-Capital Region. Each interview was recorded, transcribed literally, and analysed thematically using a grounded theory approach. RESULTS: GPs were the most important information source in this study. GPs and other professionals were considered to be reliable sources of information by the patients. All patients received information passively at diagnosis. Patients that actively sought information differed in their search behaviour and reported they were not sufficiently informed. Some information sources remained unknown to the diabetic patients in this study. CONCLUSION: Diabetic patients of the Brussels-Capital Region are not well informed about their diet. The main problem is how patients perceived the accessibility of information. Practice implications Public health strategies are required to promote well-informed, proactive patients supported by healthcare teams.