Editorial introductions

Objective: to analyze changes of serum calprotectin (CP) concentration, its relationship to the clinical and laboratory parameters of rheumatoid arthritis (RA) activity, and the significance of baseline CP level for predicting therapeutic response in RA patients treated with etanercept (ETC). Subjects and methods. A total of 84 patients with moderate and high RA activity (mean DAS28 6.35±0.92) who had been ineffectively treated with disease-modifying antirheumatic drugs were examined. The patients received ETC 50 mg/week subcutaneously for 34 weeks. To assess RA activity, tender and swollen joint count, pain, patient’s and physician’s assessment of global disease activity on 100-mm visual analogue scale and DAS28 were used. Functional status was evaluated by HAQ and RAPID3. Treatment efficacy was assessed according to the European League against Rheumatism (EULAR) criteria and the American College of Rheumatology (ACR) criteria. Serum concentration of CP was tested before, 12 and 25 weeks after start of therapy. Results and discussion. There was a statistically significant (p < 0.0001) decrease in CP concentrations after 12 weeks of ETC therapy. Later (after 25 weeks) CP level remained essentially unchanged. CP concentration correlated with erythrocyte sedimentation rate, C-reactive protein level, swollen joint count, and DAS28. Baseline CP level was not a predictor for achieving the therapeutic response according to the EULAR and ACR criteria. In a group of patients unresponsive to treatment according to the EULAR criteria, CP levelrose at 25 weeks whereas it fell during clinical improvement. In the patients achieving ACR 50 and 70% response, changes of CP level were significantly better than those in the other patients. Conclusion. ETC therapy caused a considerable reduction of CP level, clinical and laboratory parameters of RA activity. The baseline concentration of CP was not a predictor for achieving the response to ETC treatment.

Editorial introductions

BackgroundSB4 is approved by the European Commission as a biosimilar of the reference etanercept (ETN).ObjectivesTo evaluate the maintenance and improvement in clinical efficacy between week 12 and 24 in patients...

Over the last several years the two pre-eminent professional societies representing rheumatology, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), have been discussing increasing their collaboration in areas of interest to rheumatologists worldwide. These discussions resulted in a letter of agreement in 2008 on the framework whereby the two organisations would work together to develop disease classification criteria as well as recommendations for conducting of clinical trials. To enhance communication between the two organisations, ACR representatives now sit on the EULAR Standing Committee for Clinical Affairs and the EULAR Standing Committee of Epidemiology, and EULAR representatives now sit on the ACR Criteria Subcommittee and Quality of Care Committee. The first result of this effort was the joint publication, in Annals of the Rheumatic Diseases and Arthritis Care & Research , of the recommendations on reporting disease activity in clinical trials of patients with rheumatoid arthritis (RA).1 2 This document was important in that it delineated the minimal standards necessary for clinical trials evaluating new therapeutics in RA. Several collaborative projects are under way on RA, and also on gout, scleroderma, myositis and vasculitis. The positive aspects of developing a consensus between the dominant voices in world of rheumatology are self-evident. The recent initiative to revise the ACR classification criteria for RA3 is the most significant cooperation so far. For the past 2 years rheumatologists on both sides of the Atlantic have been working on this project, and the fruits of their work are …

PMS4 - RHEUMATOID ARTHRITIS TREATED WITH SIX-MONTHS OF FIRST-LINE BIOLOGIC OR BIOSIMILAR THERAPY: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Rheumatology meeting: Efficacy, safety of biologics central focus

Performance of response criteria for assessing peripheral arthritis in patients with psoriatic arthritis: analysis of data from randomised controlled trials of two tumour necrosis factor inhibitors

Anti-cyclic citrullinated peptide antibodies and IL-23p19 in psoriatic arthritis

AB0391 Cardiovascular risk assessment in rheumatoid arthritis patients using the score chart

Etanercept, a fusion protein consisting of the extracellular ligand-binding domain of the 75kD receptor for tumour necrosis factor-alpha and the constant portion of human IgG1, is administered by subcutaneous injection and is the first specific anti-cytokine therapy approved for rheumatoid arthritis. In patients with active rheumatoid arthritis [American College of Rheumatology (ACR) functional class I to III] who had failed to respond to previous treatment with > or = 1 disease-modifying antirheumatic drug (DMARD), etanercept, alone or in combination with methotrexate, produced improvements in all components included in the ACR core set of disease activity measures. A dose-response effect was apparent with etanercept 0.25 to 16 mg/m2 twice weekly in a randomised, double-blind study in 180 patients. The mean number of swollen or tender joints at the end of the 12-week study decreased by >50% in patients treated with etanercept 16 mg/m2 twice weekly and by <25% in patients treated with placebo. In a 24-week multicentre, randomised, double-blind study in 234 patients who were not allowed to use DMARDs, etanercept 10 or 25mg twice weekly had a rapid onset of effect. Significantly more patients treated with etanercept 25mg twice weekly than placebo experienced 20 (ACR 20), 50 (ACR 50) or 70% (ACR 70) improvement in ACR criteria after 3 and 6 months. Limited evidence suggests that the therapeutic effects of etanercept are maintained for up to 2 years. Etanercept 25mg twice weekly produced significant improvement in patients receiving oral or subcutaneous methotrexate 10 to 25 mg/week in a multicentre, randomised, double-blind, placebo-controlled study. A significantly greater proportion of patients treated with etanercept plus methotrexate (71%) than placebo plus methotrexate (27%) achieved the ACR 20 criteria after 6 months. Moreover, 39 and 15% of patients treated with etanercept plus methotrexate, but no placebo plus methotrexate recipients, had achieved the ACR 50 and ACR 70 criteria at this time. Etanercept 0.4 mg/kg twice weekly reduced disease activity in a preliminary, noncomparative study in 69 children aged > or =4 years with refractory juvenile rheumatoid arthritis. Although the overall frequency of infections was similar in patients treated with etanercept or placebo, upper respiratory tract infections were more common in patients treated with etanercept (29%) than placebo (16%). Injection site reactions occurred more frequently in etanercept- than placebo-treated patients, but did not bias the results of any study. When etanercept is administered alone or in combination with methotrexate in patients with refractory rheumatoid arthritis, significant reductions in disease activity occur within 2 weeks and are sustained for at least 6 months. Thus, etanercept appears to be particularly well suited for use in patients who fail to respond to treatment with DMARDs.

Objective: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). Methods: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. Results: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. Conclusion: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

Efficacy of roxithromycin in adult patients with rheumatoid arthritis who had not received disease-modifying antirheumatic drugs: A 3-month, randomized, double-blind, placebo-controlled trial

To examine the association of the American College of Rheumatology (ACR) response criteria (20% improvement [ACR20], ACR50, and ACR70) and the European League Against Rheumatism (EULAR) response criteria with patient-reported improvement in rheumatoid arthritis (RA) activity. Two hundred fifty patients with active RA were studied prospectively, before and after escalation of antirheumatic treatment. Patients were asked to report if they subjectively judged that they had experienced important improvement with treatment, and the proportion of patients who reported improvement was compared with the proportion who met the ACR20, ACR50, ACR70, and EULAR response criteria. Improvement in overall arthritis status was reported by 167 patients (66.8%), while 107 patients (42.8%) had an ACR20 response, 52 (20.8%) had an ACR50 response, 24 (9.6%) had an ACR70 response, and 136 (54.4%) had a EULAR moderate/good response. ACR20 response had a sensitivity of 0.57 and a specificity of 0.85 for clinically important improvement as judged by patients. Sensitivities of the ACR50, ACR70, and EULAR moderate/good responses were 0.30, 0.14, and 0.68, respectively, while their specificities were 0.97, 0.99, and 0.73, respectively. The ACR hybrid score with the highest sensitivity and specificity for important improvement was 19.99. Among patients with active RA, ACR20 responses are highly specific measures of improvement as judged by patients, but exclude a substantial proportion of patients who consider themselves improved. Response criteria are associated with, but not equivalent to, patient-perceived improvement.

arthritis?

Tumor necrosis factor α (TNF-α) inhibitors ranked highest in German pharmaceutical expenditure in 2011. Their most important application is the treatment of rheumatoid arthritis (RA). Our objective is to analyze cost per responder of TNF-α inhibitors for RA from the German Statutory Health Insurance funds' perspective. We aim to conduct the analysis based on randomized comparative effectiveness studies of the relevant treatments for the German setting. For inclusion of effectiveness studies, we require results in terms of response rates as defined by European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) criteria. We identify conventional triple therapy as the relevant comparator. We calculate cost per responder based on German direct medical costs. Direct clinical comparisons could be identified for both etanercept and infliximab compared to triple therapy. For infliximab, cost per responder was 216,392 euros for ACR50 and 432,784 euros for ACR70 responses. For etanercept, cost per ACR70 responder was 321,527 euros. Cost was lower for response defined by EULAR criteria, but data was only available for infliximab. Cost per responder is overestimated by 40 % due to inclusion of taxes and mandatory rebates in German drugs' list prices. Our analysis shows specific requirements for cost-effectiveness analysis in Germany. Cost per responder for TNF-α treatment in the German setting is more than double the cost estimated in a similar analysis for the USA, which measured against placebo. The difference in results shows the critical role of the correct comparator for a specific setting.