BENEFIT: real-world effectiveness of SB4 after transition from reference etanercept in rheumatoid arthritis and axial spondyloarthritis.

OBJECTIVES: The objective of this non-interventional study was to evaluate the effectiveness and safety of the etanercept biosimilar SB4 (BenepaliTM) following transition from reference etanercept in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). METHODS: Data were collected from clinical records of adult patients with stable RA or axSpA, in France, Germany, Italy and Spain. Key outcomes included the change from transition to 3 and 6 months in Disease Activity Score 28 (DAS28) for RA or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA. RESULTS: In total, 358 patients with RA and 199 patients with axSpA were enrolled. The mean individual change in disease score from transition was -0.02 (95% confidence interval [CI] -0.11, 0.08) at 3 months and 0.01 (95% CI -0.09, 0.11) at 6 months for DAS28, and -0.01 (95% CI -0.24, 0.21) at 3 months and -0.11 (95% CI -0.31, 0.10) at 6 months for BASDAI. In the RA cohort, 19 (5.3%) and 5 patients (1.4%) reported adverse events and serious adverse events (SAEs), respectively. In the axSpA cohort, 12 (6.0%) and 2 patients (1.0%) reported adverse events and SAEs, respectively. One SAE of pneumonia (RA cohort) was considered to be related to SB4 administration. At 6 months post-transition, the SB4 retention rate was 90.8% (95% CI 87.2%, 93.4%) in the RA cohort and 92.4% (95% CI 87.5%, 95.4%) in the axSpA cohort. CONCLUSIONS: Transition from reference etanercept to SB4 is effective and safe in patients with stable RA and axSpA.

Clinical utility of the ASDAS index in comparison with BASDAI in patients with ankylosing spondylitis (Axis Study).

The objective of the study was to study the clinical utility of the Ankylosing Spondylitis Disease Activity Score (ASDAS) for the assessment of disease activity in ankylosing spondylitis (AS) patients, compared to the Bath Ankylosing Spondylitis Activity Index (BASDAI). This was a prospective longitudinal observational study in patients with AS (NY-modified criteria) from 23 Spanish centers. Physical and analytical data; global, lumbar, and nocturnal pain; ASDAS, BASDAI and minimally acceptable clinical status (PASS) were collected. Psychometric characteristics of both indexes were analyzed: construct validity (convergent and divergent), discriminant capacity, criterion validity (global physician and patient assessment), and sensitivity to change. The study involved 127 patients (19.7% attrition). Both BASDAI and ASDAS showed a higher correlation with patient's global assessment (r = 0.76 and 0.70, respectively) than with physician's global assessment (r = 0.67 and 0.57). Both scores allowed discriminating patients with an acceptable clinical status, although BASDAI to a greater extent than ASDAS (Cohen δ 1.72 vs 0.88 for the medical PASS). Both scores showed sensitivity to change in patients who changed from an unacceptable symptomatic state to acceptable according to PASS criteria (physician and patient) and by BASDAI 50 response criteria (Cohen δ > 0.80). BASDAI showed better criterion validity than ASDAS, both for the patient PASS (AUC 0.85 vs 0.79) and for the physician's (AUC 0.90 vs 0.79). ASDAS shows adequate performance for disease activity in patients with AS; however, in this study, its psychometric properties do not present advantages over BASDAI in terms of criterion validity, sensitivity to change or discriminative capacity; replacement of BASDAI by ASDAS is not supported by the data.

Prevalence of fractures in women with rheumatoid arthritis and/or systemic lupus erythematosus on chronic glucocorticoid therapy.

BACKGROUND: Glucocorticoid (GC) therapy is associated with an increased risk of fractures. The main objective of this study was to determine the prevalence of undiagnosed vertebral fractures in women chronically using GC therapy for autoimmune disorders. We also determined the prevalence of non-vertebral fractures, and investigated whether factors such as quality-of-life and future fracture risk are associated with vertebral/non-vertebral fractures. METHODS: This was a multicenter cross-sectional study conducted in Spain. All women had rheumatoid arthritis (RA) and/or systemic lupus erythematosus (SLE). Radiological morphometric vertebral fractures were evaluated centrally (Genant semiquantitative method), whereas non-vertebral fractures were not assessed by radiography. Before radiography, patients were asked whether they had vertebral/non-vertebral fractures, hereafter referred to as 'self-reported' fractures. Assessment tools included the Disease Activity Score (DAS28), the SF-36 questionnaire, and FRAX®. RESULTS: Complete data were obtained for 576 outpatients with RA and/or SLE (83.3 % had RA); mean [SD] age 59.6 [15] years. Of all patients, 6.4 % had self-reported vertebral fractures, whereas 18.9 % had morphometric vertebral fractures (RA: 7.1 % self-reported vs. 20.0 % morphometric; SLE: 3.2 % self-reported vs. 13.7 % morphometric). Non-vertebral fractures were self-reported by 9.8 % of RA and 5.3 % of SLE patients. Low physical functioning was associated with morphometric vertebral fractures (mean [SD] SF-36 score 18.8 [6.0] when present vs. 20.1 [5.9] when absent; p = 0.028) and self-reported non-vertebral fractures (16.7 [5.2] when present vs. 20.1 [5.9] when absent; p < 0.001). Mean [SD] DAS28 was higher (p = 0.013) when any self-reported fractures were present (4.0 [1.3]) than absent (3.6 [1.3]). Based on FRAX® analysis, patients with vs. without morphometric vertebral fractures had higher 10-year probabilities of major osteoporotic fractures (mean [SD] 17.9 [12.9]% vs. 9.9 [9.6]%; p < 0.001) and hip fractures (11.0 [11.7]% vs. 4.6 [8.1]%; p < 0.001). CONCLUSIONS: Morphometric vertebral fractures were detected in 18.9 % of patients, i.e. 3-times more frequently than verbally reported by patients. Patients with vs. without fractures had worse quality-of-life and increased fracture risk. Accordingly, it is of utmost importance that women chronically using GCs are assessed for fractures, including morphometric vertebral fractures.

Real-world apremilast use in biologic-naïve psoriatic arthritis patients. Data from Spanish clinical practice.

INTRODUCTION: Apremilast is approved for treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on apremilast effectiveness in clinical practice is limited. METHODS: Observational study enrolling adult patients, across 21 Spanish centres, who had initiated apremilast in the prior 6 (±1) months and were biologic naive. Data were collected at routine follow-up visits 6 and 12 months after apremilast initiation. Primary outcome was 6 and 12-month persistence to apremilast. Secondary outcomes included Disease Activity for PsA (DAPSA), joint erosions, enthesitis, dactylitis, and patient-reported quality of life (QoL, measured using the PsA impact of disease [PsAID] questionnaire). RESULTS: We included 59 patients. Most had oligoarticular PsA, moderate disease activity, and high comorbidity burden. Three-quarters were continuing apremilast at 6 months and two-thirds at 12 months; mean (SD) apremilast treatment duration was 9.43 (1.75) months. DAPSA scores showed improved disease activity: one-third of patients in remission or low activity at apremilast initiation versus 62% and 78% at 6 and 12 months, respectively. Eleven of 46 patients with radiographic assessments had joint erosions at apremilast initiation and none at month 12. Median (Q1, Q3) number of swollen joints was 4.0 (2.0, 6.0) at apremilast initiation versus 0.0 (0.0, 2.0) at 12 months. Incidence of dactylitis and enthesitis decreased between apremilast initiation (35.6% and 28.8%, respectively) and month 12 (11.6% and 2.4%, respectively). Over two-thirds of patients had a PSAID-9 score <4 (cut-off for patient-acceptable symptom state) at month 12. CONCLUSIONS: In Spanish clinical practice, two-thirds of PsA patients continued apremilast at 12 months, with clinical benefits at the joint level, no radiographic progression of erosions, and a positive impact on patient-reported QoL. Trial registration number Clinicaltrials.gov: NCT03828045.

SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 1: Epidemiology, risk factors and prognosis.

OBJECTIVE: To develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. RESULTS: Six PICO questions were selected, three of which analysed the incidence and prevalence of RA-ILD, associated risk factors, and predictors of progression and mortality. A total of 6 specific recommendations on these topics, structured by question, were formulated based on the evidence found and/or expert consensus. CONCLUSIONS: We present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions and facilitate decision-making for patients.

SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 2: Treatment.

OBJECTIVE: To develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. RESULTS: Six PICO questions were selected, three of which analysed the safety and effectiveness of glucocorticoids, classical synthetic disease-modifying anti-rheumatic drugs (DMARDs) and other immunosuppressants, biological agents, targeted synthetic DMARDs, and antifibrotic therapies in the treatment of this complication. A total of 12 recommendations were formulated based on the evidence found and/or expert consensus. CONCLUSIONS: We present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions, reduce clinical healthcare variability, and facilitate decision-making for patients.

Update of the Position Paper of the Spanish Society of Rheumatology on Biosimilar Drugs. / Actualización del Documento de posicionamiento de la Sociedad Española de Reumatología sobre fármacos biosimilares.

In 2015 the Spanish Society of Rheumatology (Sociedad Española de Reumatología [SER]) published its position paper on biosimilar drugs. In this update, the SER, continues to manifest its unequivocal commitment to the sustainability of the health system of our country and is aligned with the measures that, without reducing quality of care, are aimed at ensuring its continuity. Since the publication of the previous position paper, the European Commission has authorized new biosimilar drugs, which provides an excellent opportunity to advance the efficiency of health care. In this new scenario of increased therapeutic offer of biologics, the SER considers it crucial to preserve the freedom of prescription of physicians who prescribe drugs based exclusively on the characteristics and individual circumstances of each patient, without forgetting the economic aspects there of.

SER recommendations on the use of biological drugs in primary Sjögren's syndrome. / Recomendaciones SER sobre la utilización de fármacos biológicos en el síndrome de Sjögren primario.

OBJECTIVE: To formulate SER recommendations for the use of biological agents in primary Sjögren's syndrome (pSS). METHODS: Relevant clinical research questions were identified on the use of biological agents in pSS. The clinical questions were reformulated into 4PICO questions. A search strategy was designed and a review of the scientific evidence of studies published until May 2017 was carried out. The scientific evidence available was systematically reviewed. The overall level of scientific evidence was assessed using the SIGN evidence levels. After that, specific recommendations were made. RESULTS: Rituximab is recommended as the biological agent of choice for extraglandular manifestations refractory to conventional treatment. The use of anti-TNF agents is discouraged. The scientific evidence with belimumab and abatacept is scarce, so they should be considered only in cases refractory to rituximab. CONCLUSIONS: Rituximab is the biological agent of choice in severe extraglandular manifestations of pSS. Belimumab or abatacept may be useful in selected cases.

Position paper from the Spanish Society of Rheumatology on biosimilar drugs.

A biosimilar (BS) is a biological drug that contains a version of the active substance of an already authorized original biological product. The BSs are marketed after patent period of the original drug has ended and once it has been demonstrated that the differences regarding the innovative medicine have no relevant effect on its safety or clinical efficacy. The Spanish Society of Rheumatology, in line with the European Medicines Agency, considers that because of its nature and complexity of production, a BS cannot be considered to be the same as a generic drug. The Spanish Society of Rheumatology expresses an unequivocal commitment to the sustainability of the health system in our country and our steadfast alignment with all measures designed to ensure continuity, without reducing the quality of care. Therefore, we believe that the advent of BSs will likely facilitate access of patients with rheumatic diseases to the biological drugs. This article reviews the European Medicines Agency requirements for authorization, the Spanish legal framework and controversies on BS and presents the position paper of the Spanish Society of Rheumatology on these drugs.

[Soft-tissue infections]. / Infección de partes blandas.

One of the soft-tissue infections with a large clinical relevance is necrotizing fascitis produced by Streptococcus pyogenes and skin infections produced by Staphylococcus aureus, particularly due to the evermore frequent methylcillin (MRSA) resistant varieties. In necrotizing fascitis the diagnostic delay as well as the delay in the indication for surgical debridement influence both the prognosis and a high mortality related to these infections. Two clinical forms have been described: Type I caused by at least one anaerobic species in combination with facultative anaerobes, more frequent in diabetics or patients with peripheral vascular disease; type II, monomicrobial, produced by group A beta hemolytic Streptococcus and with a lesser frequency by Staphylococcus aureus. Among the recognized risk factors diabetes mellitus, peripheral vascular disease, chronic renal failure, alcoholism, cancer, malnutrition, steroid and/or immunosuppressant treatment and the use of intravenous parenteral drugs are widely recognized. Therapeutics is based on hemodynamic support, antibiotic therapy and an early surgical approach with the elimination of all of the necrotic and devitalized tissue. Infections frequently associated to community-acquired MRSA are those present in skin and soft-tissue. Some population groups have been described as at-risk, but there is also an increase in the number of patients with no risk factors. Also, national and international registries of anti-TNF therapies have demonstrated the increase of soft-tissue infections in patients with rheumatoid arthritis treated with these agents. Other biologic drugs such as rituximab, abatacept or anakinra do not seem to be associated to an increase in these infections.