Subcutaneous abatacept for the treatment of rheumatoid arthritis in routine clinical practice in Germany, Austria, and Switzerland: 2-year retention and efficacy by treatment line and serostatus.

INTRODUCTION/OBJECTIVES: The ASCORE study on treatment for rheumatoid arthritis (RA) showed better retention and clinical response rates for abatacept as first-line versus later-line therapy. This post hoc analysis of ASCORE assessed 2-year retention, efficacy, and safety of subcutaneous (SC) abatacept in Germany, Austria, and Switzerland. METHODS: Adults with RA who initiated SC abatacept 125 mg once weekly were assessed. Primary endpoint was abatacept retention rate at 2 years. Secondary endpoints: proportions of patients with low disease activity (LDA)/remission per Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (≤ 3.2), Simplified Disease Activity Index (≤ 11), and Clinical Disease Activity Index (≤ 10). Outcomes were analyzed by treatment line and serostatus. RESULTS: For the pooled cohort, the 2-year abatacept retention rate was 47.6%; retention was highest in biologic-naïve patients (50.5% [95% confidence interval 44.9, 55.9]). Patients seropositive for both anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; + / +) at baseline had a higher 2-year abatacept retention rate than patients with single seropositivity for either APCA or RF or double-seronegativity (- / -), irrespective of treatment line. At 2 years, a higher proportion of patients who were biologic-naïve were in LDA/remission than patients with one or ≥ two prior biologics. CONCLUSION: A higher proportion of patients with + / + RA (compared with - / - RA) had abatacept retention after 2 years. Early identification of patients with seropositive RA may facilitate a precision-medicine approach to RA treatment, leading to a higher proportion of patients in LDA/remission. TRIAL REGISTRATION NUMBER: NCT02090556; date registered: March 18, 2014 (retrospectively registered). Key Points • This post hoc analysis of a German-speaking subset of European patients with RA from the global ASCORE study (NCT02090556) showed that retention of SC abatacept within this subset was 47.6%, with good clinical outcomes after 2 years. • Patients with double-seropositive RA (ACPA and RF positive) had higher retention of abatacept than patients with double-seronegative RA (ACPA and RF negative). Retention and clinical responses were highest for patients who were biologic-naïve compared with patients who had one or ≥ two prior biologic treatments. • These real-world data may be useful for clinicians in informing individualized treatment pathways for patients with RA, and fostering superior disease control and clinical outcomes.

[Lower Back Pain - Specific or Non-Specific?] / Rückenschmerzen.

Lower Back Pain - Specific or Non-Specific? Abstract. Lower back pain is a challenge. A diagnosis that is as accurate as possible is significant for both the treating physician and the patient. With a precise examination, it is often possible to narrow down even the less specific back pain (the so-called "non-specific back pain") and assign it to a clinical syndrome.

Disease activity dynamics in rheumatoid arthritis: patients' self-assessment of disease activity via WebApp.

Objectives: The aim was to evaluate patient self-assessment of RA disease activity in terms of Routine Assessment of Patient Index Data (RAPID) scores via a Web-based smartphone application (WebApp). Methods: In this prospective, multicentre study, adult RA patients were examined by a rheumatologist at baseline and after 3 months. Patients were asked to complete WebApp questionnaires weekly. The time course of patient-assessed RAPID3/4 scores and their correlations with rheumatologist-assessed DAS28, as well as Clinical and Simplified Disease Activity Indices (CDAI/SDAI), were evaluated. Results: Eighty patients were included in the analysis (median RA duration, 4.5 years; age, 57 years; 59% female). At baseline, there was a moderate to strong correlation between RAPID3 and DAS28 (r = 0.63), CDAI (r = 0.65) and SDAI (r = 0.61) scores. Similar or stronger correlations were seen at the 3-month follow-up visit (DAS28 r = 0.66, CDAI r = 0.71 and SDAI r = 0.61). Similar correlations were seen between RAPID4 and rheumatologist assessments. Correlations were not influenced by demographics or RA treatment. In the 3-month period, the RAPID3 score changed into a higher severity category than the category at baseline at least once in 47% of patients. When DAS28 scores were predicted from the RAPID3, 11% of patients had an increase of > 1 DAS28 unit during the 3-month observation period. Conclusion: Web-based patient assessments were strongly correlated with rheumatologist assessments of RA activity and showed considerable variation during follow-up. This provides a rationale for further exploration of their use as cost-effective tools to monitor RA activity between outpatient visits and to optimize tight control strategies.

RAISE - rheumatoid arthritis independent Swiss treatment expectations and outcome: results for the abatacept subpopulation.

QUESTIONS UNDER STUDY: Clinical trials do not necessarily reflect the results obtained in daily clinical practice. By conducting a non-interventional, observational study with biologics in rheumatoid arthritis (RA) patients in Switzerland, we aimed to generate real-world data on reasons for treatment initiation and discontinuation, physicians' expectations for treatment, co-medication, and various treatment outcome parameters. METHODS: Sixty-nine patients with a confirmed diagnosis of RA were included in this non-interventional observational study. Participating physicians used standardised questionnaires to collect data on the use of biologics at three visits over one year. Due to the small sample size of patients receiving biologics other than abatacept, only patients treated with abatacept were considered for analysis. RESULTS: The population receiving intravenously administered abatacept consisted of 56 patients. Of these, 25% received abatacept as a first-line biologic therapy. The retention rate over one year was high (75%) and similar to what has been previously observed in randomised clinical trials. Overall, abatacept was found to be effective in patients irrespective of their baseline disease activity or levels in C-reactive protein and erythrocyte sedimentation rate. Moreover, the use of glucocorticoids was found to be reduced under therapy. There was a tendency for better treatment outcomes and physicians' satisfaction with abatacept the earlier the drug was used in the sequence of biologic therapies. CONCLUSIONS: The present study suggests that abatacept is an effective and well tolerated treatment in RA patients in routine clinical practice, irrespective of disease parameter at baseline.

Development and psychometric properties of a joint protection self-efficacy scale.

INTRODUCTION: Self-efficacy is one of the most powerful determinants of behaviour change. To increase effectiveness of joint protection (JP) education, it may be important to address perceptions of JP self-efficacy directly. The aim of this study was to develop a scale to measure JP self-efficacy (JP-SES) in people with rheumatoid arthritis (RA). METHODS: Instrument development included item generation, construct validity, and reliability testing. Rasch analysis was applied to determine construct validity and the revised JP-SES was tested again to confirm validity and establish test-retest reliability and internal consistency. RESULTS: A total of 46 items were generated by literature review, occupational therapists, and people with RA. After semi-structured interviews and field-testing with RA participants, a 26-item questionnaire draft was constructed and tested. Rasch analysis to determine construct validity reduced the JP-SES to 13 items with good overall fit values. Rasch analysis of confirmatory validity resulted in a final 10-item version of the JP-SES. Test-retest results supported the validity of the scale, with high internal consistency (α = 0.92) and good test-retest reliability (r(s) = 0.79; p < 0.001). CONCLUSIONS: The JP-SES is a valid and reliable scale to assess perceived ability of people with RA to apply JP methods. The JP-SES could help stimulate the use of efficacy-enhancing methods in JP education.

Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis.

BACKGROUND: The excess in cardiovascular risk in patients with rheumatoid arthritis provides a strong rationale for early therapeutical interventions. In view of the similarities between atherosclerosis and rheumatoid arthritis and the proven benefit of angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease, it was the aim of the present study to delineate the impact of ramipril on endothelial function as well as on markers of inflammation and oxidative stress in patients with rheumatoid arthritis. METHODS AND RESULTS: Eleven patients with rheumatoid arthritis were included in this randomized, double-blind, crossover study to receive ramipril in an uptitration design (2.5 to 10 mg) for 8 weeks followed by placebo, or vice versa, on top of standard antiinflammatory therapy. Endothelial function assessed by flow-mediated dilation of the brachial artery, markers of inflammation and oxidative stress, and disease activity were investigated at baseline and after each treatment period. Endothelial function assessed by flow-mediated dilation increased from 2.85+/-1.49% to 4.00+/-1.81% (P=0.017) after 8 weeks of therapy with ramipril but did not change with placebo (from 2.85+/-1.49% to 2.84+/-2.47%; P=0.88). Although systolic blood pressure and heart rate remained unaltered, diastolic blood pressure decreased slightly from 78+/-7 to 74+/-6 mm Hg (P=0.03). Tumor necrosis factor-alpha showed a significant inverse correlation with flow-mediated dilation (r=-0.408, P=0.02), and CD40 significantly decreased after ramipril therapy (P=0.049). CONCLUSIONS: Angiotensin-converting enzyme inhibition with 10 mg/d ramipril for 8 weeks on top of current antiinflammatory treatment markedly improved endothelial function in patients with rheumatoid arthritis. This finding suggests that angiotensin-converting enzyme inhibition may provide a novel strategy to prevent cardiovascular events in these patients.

Glucocorticoid therapy-induced memory deficits: acute versus chronic effects.

Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 +/- 1.0 years, mean +/- SE) with low to moderate doses of prednisone (7.5 +/- 0.8 mg, mean +/- SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.

F-18 FDG whole-body PET for the assessment of disease activity in patients with rheumatoid arthritis.

UNLABELLED: PURPOSE OF REPORT: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used to image synovitis in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate if a simple scoring system based on visual assessment of FDG joint uptake correlates with the clinical assessment of patients with RA undergoing antiinflammatory treatment. MATERIALS AND METHODS: Seven patients with active RA underwent whole-body FDG PET and clinical assessment before and after treatment with the antitumor necrosis factor alpha antibody (infliximab). A PET total joint score, ie, the sum of all scores based on FDG uptake intensity between zero and 4 in 28 joints, was correlated with a total joint score based on the clinical disease activity in the same joints using a Spearman rank correlation. RESULTS: The PET based total joint score was similarly high before onset as was the clinical total joint score. The decrease of FDG joint uptake in the follow-up PET scans correlated significantly with the clinical assessment. Additionally, synovial FDG uptake was found in extraarticular sites such as tendon sheaths and bursae. CONCLUSIONS: Visual assessment of FDG uptake shows a significant correlation with clinical evaluation of disease activity in patients with RA undergoing antiinflammatory treatment.

The effectiveness of anti-tumor necrosis factor therapy in preventing progressive radiographic joint damage in rheumatoid arthritis: a population-based study.

OBJECTIVE: To compare the effectiveness of 3 therapeutic strategies in preventing progressive joint damage, in a population-based cohort. The 3 strategies were infliximab with concomitant disease-modifying antirheumatic drugs (DMARDs), etanercept with concomitant DMARDs, and etanercept alone. METHODS: We used sequential radiographs to assess all patients who were treated with infliximab or etanercept for >10 months. The rates of erosion progression and joint space narrowing (JSN) were analyzed using multivariate regression models for longitudinal data, with adjustment for potential confounders. RESULTS: A total of 372 patients treated with anti-tumor necrosis factor (TNF) therapies met the inclusion criteria. The baseline characteristics of the patients assigned to the 3 strategies were not significantly different, except that, as expected, more patients were receiving combination therapy with infliximab. The combination of infliximab plus DMARDs was significantly more effective than etanercept alone for controlling erosion progression (P < 0.001), but the effectiveness of the 2 combination-treatment strategies was similar (P = 0.07). The combination of infliximab plus DMARDs was also more effective at controlling progressive JSN compared with etanercept alone (P = 0.04) or etanercept plus DMARDs (P = 0.02). Treatment with anti-TNF agents (infliximab or etanercept) plus concomitant DMARDs was more effective than treatment with etanercept alone for controlling erosion progression (P = 0.045). CONCLUSION: When combined with traditional DMARDs, both etanercept and infliximab appear to offer similar protection against progressive structural joint damage, and combination therapy with either of these agents appears to be more effective than treatment with etanercept alone.

Microcirculation abnormalities in patients with fibromyalgia - measured by capillary microscopy and laser fluxmetry.

This unblinded preliminary case-control study was done to demonstrate functional and structural changes in the microcirculation of patients with primary fibromyalgia (FM). We studied 10 women (54.0 +/- 3.7 years of age) with FM diagnosed in accordance with the classification criteria of the American College of Rheumatology, and controls in three groups (n = 10 in each group) - age-matched women who were healthy or who had rheumatoid arthritis or systemic scleroderma (SSc). All 40 subjects were tested within a 5-week period by the same investigators, using two noninvasive methods, laser fluxmetry and capillary microscopy. The FM patients were compared with the healthy controls (negative controls) and with rheumatoid arthritis patients and SSc patients (positive controls). FM patients had fewer capillaries in the nail fold (P < 0.001) and significantly more capillary dilatations (P < 0.05) and irregular formations (P < 0.01) than the healthy controls. Interestingly, the peripheral blood flow in FM patients was much less (P < 0.001) than in healthy controls but did not differ from that of SSc patients (P = 0.73). The data suggest that functional disturbances of microcirculation are present in FM patients and that morphological abnormalities may also influence their microcirculation.

Expression of interleukin-21 receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis.

OBJECTIVE: To determine the role and expression of the cytokine/receptor pair interleukin-21 (IL-21)/IL-21 receptor (IL-21R) in rheumatoid arthritis (RA). METHODS: The expression of IL-21R and IL-21 was analyzed by TaqMan real-time polymerase chain reaction (PCR) and in situ hybridization of synovial biopsy samples from patients with RA and osteoarthritis (OA). Double labeling by immunohistochemistry after in situ hybridization was performed with anti-CD68 antibodies. The expression of IL-21R at the protein level was confirmed by Western blotting. Stimulation experiments were performed with recombinant IL-1beta, tumor necrosis factor alpha (TNFalpha), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGFbeta). The role of IL-21R in cartilage destruction was analyzed in the SCID mouse coimplantation model of RA. RESULTS: IL-21R was found in total RNA extracts and in synovial biopsy samples from RA patients, whereas no expression or only minimal expression was seen in samples from OA patients. Double labeling indicated that both synovial macrophages and synovial fibroblasts expressed IL-21R. Western blotting with anti-IL-21R antibodies confirmed the expression of IL-21R protein in RA synovial fibroblasts (RASFs). Of note, IL-21 was not detectable by real-time PCR and in situ hybridization in the same samples in vivo as in vitro. The level of expression of IL-21R messenger RNA (mRNA) was not altered by stimulation with IL-1beta, TNFalpha, PDGF, or TGFbeta. Interestingly, in the SCID mouse coimplantation model, RASFs did not maintain their expression of IL-21R at sites of invasion into the cartilage. Similarly, IL-21R mRNA was not expressed at sites of invasion into cartilage and bone in RA synovium. CONCLUSION: Our data demonstrate that IL-21R is expressed in RA synovium by RASFs and synovial macrophages. IL-21R is associated with the activated phenotype of RASFs independently of the major proinflammatory cytokines IL-1beta and TNFalpha, but correlates negatively with the destruction of articular cartilage and bone.

Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-alpha in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-alpha antibody infliximab on disease activity and endothelial function in patients with active RA. METHODS AND RESULTS: Eleven RA patients (mean age 46+/-5 years; disease duration 9+/-2 years) with high disease activity despite treatment with stable doses of methotrexate (