Clinical and therapeutic management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: RADAR study.

To describe the clinical and therapeutic management of rheumatoid arthritis (RA) patients with biological disease-modifying antirheumatic drugs (bDMARDs), alone or in combination with conventional synthetic DMARDs (csDMARDs), as well as analysing changes over time in bDMARD use. An observational, retrospective, multicentre study was conducted in the rheumatology departments of 10 public Spanish hospitals. Patients with RA treated with bDMARDs at baseline who had medical records available in the data collection period 2013-2016 were included. All visits to rheumatology departments recording any type of bDMARD modification (dose, etc.) were collected. Clinical characteristics, concomitant treatment, resource use, work productivity and quality of life (QoL) were recorded. 128 patients were included: 81 received first-line bDMARD treatment, 28 second-line bDMARD treatment and 19 received third or later lines. Mean study follow-up was 4.1 years. Assessment of DAS28 was available in 54.6% of visits. At baseline, 48.7% of patients had moderate-high disease activity. At final observation, 69.5% of patients continued with the first bDMARD. Tumour necrosis factor blockers were administered to 85.2% of patients in first line, 45.7% in second line and 18.1% in third or later lines. At final observation, 80.2% of patients still felt pain/discomfort. As expected, those with higher disease activity had higher loss of work productivity and lower QoL, as assessed by DAS28, than patients with lower disease activity. Drugs represented 82.6% of the total cost. In this Spanish cohort of 128 patients, most patients remained on the first prescribed bDMARD, despite remaining signs and symptoms.

Geographic Analysis of the Safety and Efficacy of Filgotinib in Rheumatoid Arthritis.

INTRODUCTION: Global clinical trials in rheumatoid arthritis (RA) often do not recruit enough patients from diverse racial and ethnic backgrounds to identify any potential differences in treatment outcome across such groups. To overcome this limitation, using data from five previous clinical trials and two ongoing trial extensions, this study aimed to assess the efficacy and safety of filgotinib in patients with RA across geographic regions. METHODS: This was a post hoc, exploratory analysis of data from male and female patients with RA meeting the 2010 RA criteria as defined by the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology. Data were analyzed from phase 2 (DARWIN 1-2) and phase 3 (FINCH 1-3) clinical trials, as well as two long-term extension studies (DARWIN 3, FINCH 4), of filgotinib. Efficacy endpoints included ACR 20%/50%/70% improvement (ACR20/50/70) responses, disease activity score in 28 joints using C-reactive protein [DAS28(CRP)], Clinical Disease Activity Index scores, Boolean remission, and change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety data were presented as exposure-adjusted incidence rates per 100 patient-years of exposure of treatment-emergent adverse events. RESULTS: Compared with placebo, at week 12 a greater proportion of patients receiving filgotinib 200 mg (FIL200) or 100 mg (FIL100) achieved ACR20 (p < 0.01), with similar outcomes in most regions. Overall, the reduction in HAQ-DI with FIL200 or FIL100 was greater than with placebo (p < 0.05) at week 12. Compared with placebo, at week 24 the proportions of patients achieving DAS28(CRP) ≤ 3.2 were greater for both doses of FIL, as seen in most regions (p < 0.01). Safety outcomes did not indicate regional or ethnic differences in the safety profile of filgotinib. CONCLUSION: Filgotinib efficacy and safety in patients with RA were generally consistent across geographic regions. GOV TRIAL REGISTRATION NUMBERS: NCT02889796; NCT02873936; NCT02886728; NCT03025308; NCT01888874; NCT01894516; NCT02065700.

Clinical trials in rheumatoid arthritis recruit too few patients from diverse ethnic backgrounds to be able to identify differences in treatment outcomes. In adults with moderate-to-severe active rheumatoid arthritis who do not tolerate or have responded poorly to other advanced treatments, the Janus kinase inhibitor filgotinib can be used alone or in combination with the immunosuppressant methotrexate. Using data from 4695 patients with rheumatoid arthritis from five previous clinical trials and two ongoing trial extensions, this paper examined the efficacy and safety of filgotinib in patients with rheumatoid arthritis across geographic locations worldwide.Patients were grouped by region: North America, South and Central America, Western Europe, Eastern Europe, East Asia, South and Southeast Asia, and Other (South Africa, New Zealand, Australia, and Israel). The efficacy of filgotinib in treating the symptoms of rheumatoid arthritis was assessed using several measures of disease activity, with changes in patient quality of life determined using a health assessment questionnaire. Safety data were reported as the rates of side effects experienced by patients.Across different geographic regions, no major differences in filgotinib treatment response were observed. Rheumatoid arthritis disease activity levels were consistently lower in patients receiving filgotinib than in patients receiving placebo. Across the regions examined, quality-of-life scores also improved to a greater degree in patients receiving filgotinib compared with placebo. The rates of side effects, including infections, were similar irrespective of region. The number of deaths was low, mostly resulting from cardiovascular events, infections, and malignancies.This study demonstrates that the efficacy and safety of filgotinib are consistent in patients with rheumatoid arthritis from a broad range of geographic regions and ethnic backgrounds.

Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension.

Objective: Evaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE). Methods: During the 48-week OLE, patients received sarilumab 200 mg subcutaneously once every 2 weeks. Safety (March 2017 cut-off) and efficacy, including patient-reported outcomes, were evaluated. Results: In the double-blind phase, patients receiving sarilumab or adalimumab monotherapy showed meaningful improvements in disease activity; sarilumab was superior to adalimumab for improving signs, symptoms and physical function. Overall, 320/369 patients completing the 24-week double-blind phase entered OLE (155 switched from adalimumab; 165 continued sarilumab). Sarilumab safety profile was consistent with previous reports. Treatment-emergent adverse events were similar between groups; no unexpected safety signals emerged in the first 10 weeks postswitch. Among switch patients, improvement in disease activity was evident at OLE week 12: 47.1%/34.8% had changes ≥1.2 in Disease Activity Score (28 joints) (DAS28)-erythrocyte sedimentation rate/DAS28-C-reactive protein. In switch patients achieving low disease activity (LDA: Clinical Disease Activity Index (CDAI) ≤10; Simplified Disease Activity Index (SDAI) ≤11) by OLE week 24, 70.7%/69.5% sustained CDAI/SDAI LDA at both OLE weeks 36 and 48. Proportions of switch patients achieving CDAI ≤2.8 and SDAI ≤3.3 by OLE week 24 increased through OLE week 48. Improvements postswitch approached continuation-group values, including scores ≥normative values. Conclusions: During this OLE, there were no unexpected safety issues in patients switching from adalimumab to sarilumab monotherapy, and disease activity improved in many patients. Patients continuing sarilumab reported safety consistent with prolonged use and had sustained benefit.

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study.

OBJECTIVES: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). METHODS: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. RESULTS: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. CONCLUSIONS: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal.

Status of private rheumatology in Spain. / Estado de la reumatología privada en España.

INTRODUCTION: Rheumatologic care is offered by the National Health System in Spain. However, more than a quarter of health spending is carried out in private medicine. Currently, there are no data about the number of rheumatologists with private activity in Spain. OBJECTIVES: To evaluate the number of rheumatologists with private activity in Spain and to describe the profile and location of these professionals. MATERIAL AND METHODS: A survey was developed and sent from the SER Commission on Private Practice to all SER active members. Data collection ends in December 2014. A descriptive statistical analysis and comparison of results was done. RESULTS: 759 answers from a total of 980 surveys sent (77.45%) were obtained; 38% of Spanish rheumatologists have private activity; 13% exclusively private practice and 25% private practice shared with his or her public activity. The private practice rheumatologist profile is: male, 49 years old with 19 years of experience after finishing the specialty and with a working day of 42hours per week. There is a clear predominance of private practice in the Autonomous Community of Catalonia with 28% of the total, followed by Madrid 18%, Andalusia 12% and Valencia 8%. CONCLUSIONS: 38% of Spanish rheumatologists are working in private practice. The profile of professionals working in private practice is different from that of those who work exclusively in public health. Private rheumatology is located in all regions, although most private rheumatologists are located in the regions of Catalonia, Madrid, Valencia and Andalusia, representing more than 50% of the total.

REDOSER project: optimising biological therapy dose for rheumatoid arthritis and spondyloarthritis patients.

BACKGROUND: Reducing the dose of biological therapy (BT) when patients with immune-mediated arthritis achieve a sustained therapeutic goal may help to decrease costs for national health services and reduce the risk of serious infection. However, there is little information about whether such a decision can be applied universally. Therefore, the objective of this study was to develop appropriateness criteria for reducing the dose of BT in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and peripheral spondyloarthritis (pSpA). METHODS: The RAND/UCLA appropriateness method was coordinated by experts in the methodology. Five rheumatologists with clinical research experience in RA and/or SpA selected and precisely defined the variables considered relevant when deciding to reduce the dose of BT in the 3 diseases, in order to define patient profiles. Ten rheumatologists with experience in prescribing BT anonymously rated each profile on a scale of 1 (completely inappropriate) to 9 (completely appropriate) after revising a summary of the evidence obtained from 4 systematic literature reviews carried out specifically for this project. FINDINGS: A total of 2,304 different profiles were obtained for RA, 768 for axSpA, and 3,072 for pSpA. Only 327 (14.2%) patient profiles in RA, 80 (10.4%) in axSpA, and 154 (5%) in pSpA were considered appropriate for reducing the dose of BT. By contrast, 749 (32.5%) patient profiles in RA, 270 (35.3%) in axSpA, and 1,243 (40.5%) in pSpA were considered inappropriate. The remaining profiles were considered uncertain. INTERPRETATION: Appropriateness criteria for reducing the dose of BT were developed in 3 inflammatory conditions. These criteria can help clinicians treating these disorders to optimize the BT dose. However, further research is needed, since more than 50% of the profiles were considered uncertain and the real prevalence of each profile in daily clinical practice remains unknown.

Improving inflammatory arthritis management through tighter monitoring of patients and the use of innovative electronic tools.

Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists.

Diagnostic usefulness of synovial vascular morphology in chronic arthritis. A systematic survey of 100 cases.

OBJECTIVES: To assess the diagnostic usefulness of the systematic analysis of synovial vascular morphology in various inflammatory, early, and longstanding arthropathies, and to examine the validity of the vascular patterns in predicting the evolution of a group of patients with undifferentiated arthritis (UA). METHODS: One hundred patients who underwent rheumatologic arthroscopy of a symptomatic joint (85 knees, 11 wrists, 3 elbows, 1 metacarpophalangeal joint) were evaluated. The same observer, blinded to patient diagnosis, analyzed the video recordings of the arthroscopies. Vascular morphology was classified into 3 patterns: straight, tortuous, and mixed. RESULTS: Eighty-one patients had inflammatory arthritis: 35 rheumatoid arthritis (RA), 16 psoriatic arthritis (PsA), 13 spondyloarthropathies (SpA), and 17 UA. Forty-nine percent of patients with RA had a straight pattern, 28% a mixed, and 23% a tortuous one. The sensitivity rate of the straight pattern for RA was 77% and the specificity rate was 70%. Seventy-six percent of RA patients with a straight pattern were rheumatoid factor positive (RF+) against 25% of RA patients with a tortuous pattern. The odds ratio for RA associated to straight compared with tortuous pattern was 57.3 (95% confidence interval, 6.6 to 499.5; P <.001). Patients with PsA and SpA shared the same pattern and were analyzed as 1 group. Ninety-three percent of patients with PsA/SpA had a tortuous pattern, 4% a straight pattern, and 3% a mixed pattern. The sensitivity rate of the tortuous pattern for PsA/SpA was 61% and the specificity rate was 95%. During 2 years of follow-up, 6 of 17 patients with UA were definitely diagnosed: 4 RA (2 RF+ and straight pattern; 2 with a tortuous pattern, 1 with RF+ and HLA-B27+); 1 SpA and 1 PsA, both with a tortuous pattern. No differences in vascular patterns were observed according to disease duration. Our results indicate that vascular patterns are not modified by disease modifying antirheumatic drug (DMARD) treatment. The other 19 patients had osteoarthritis (n = 8) and calcium pyrophosphate dihydrate crystal deposition disease (n = 11) and their predominant vascular pattern was tortuous-like. CONCLUSIONS: Arthroscopic assessment of synovial vascular changes in chronic arthritis may be of diagnostic and pathogenetic interest, although differences between published studies suggest a need for consensus in evaluating vascular patterns. A straight pattern is strongly associated with RF + RA whereas a tortuous pattern is generally associated with PsA or SpA; these associations are independent of disease duration. The vascular pattern likely does not change qualitatively with DMARD therapy. The application of this technique to the diagnosis or prognosis of patients with UA may be a complementary tool for the treatment of these patients, but larger, prospective studies are necessary to confirm this hypothesis.

Quality standards in a rheumatology Day-Care Hospital Unit. The proposal of the Spanish Society of Rheumatology Day Hospitals' Working Group.

BACKGROUND: In recent years, the Rheumatology Day-Care Hospital Units (DHU have undergone extensive development. However, the quality standards are poorly documented and mainly limited to structure items rather than including broad and specific areas of this specialty. OBJECTIVE: To develop specific quality standards for Rheumatology DHU. METHODS: After a systematic review of the literature and related documents, a working group (WG) involving 8 DHU-experienced rheumatologists developed an initial proposal of the quality standards, under the supervision of an expert methodologist. A second round was held by the WG group to review the initial proposal and to consider further suggestions. Once the content was agreed upon by consensus, a final report was prepared. RESULTS: 17 structure standards, 25 process standards and 10 results standards were defined, with special emphasis on specific aspects of the Rheumatology DHU. The proposal includes: 1) essential standards to 2) excellent standards, 3) a Rheumatology DHU services portfolio and 4) performance criteria. CONCLUSIONS: The proposed quality standards are the basis for developing the indicators and other management tools for Rheumatology DHU, thereby ensuring a patient-oriented practice based on both the evidence and the experience.

Effects of smoking on disease activity and radiographic progression in early rheumatoid arthritis.

OBJECTIVE: To analyze the effects of cigarette smoking on disease activity and radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: Study subjects were 156 patients with early RA (< 2 yrs). Disease activity, therapeutic response, and radiographic progression were compared in smokers and nonsmokers at 24 months. RESULTS: At baseline, ever-smokers had earlier disease onset and a closer association with the shared epitope (SE), but not more seropositive disease. No significant differences were observed in disease activity and European League Against Rheumatism therapeutic responses between smokers and nonsmokers. Multivariate analysis showed that baseline Larsen score, the HLA-DRB*04 genotype, being female, and current smoking were associated with radiographic progression. CONCLUSION: In patients with early RA, smoking was associated with earlier disease onset and the SE. Smoking was an independent factor of radiographic progression.