Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

Management of Specific Clinical Profiles in Axial Spondyloarthritis: An Expert's Document Based on a Systematic Literature Review and Extended Delphi Process.

INTRODUCTION: The management of specific clinical scenarios is not adequately addressed in national and international guidelines for axial spondyloarthritis (axSpA). Expert opinions could serve as a valuable complement to these documents. METHODS: Seven expert rheumatologists identified controversial areas or gaps of current recommendations for the management of patients with axSpA. A systematic literature review (SLR) was performed to analyze the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs (csDMARDs, b/tsDMARDs) in axSpA regarding controversial areas or gaps. In a nominal group meeting, the results of the SLR were discussed and a set of statements were proposed. A Delphi process inviting 150 rheumatologists was followed to define the final statements. Agreement was defined as if at least 70% of the participants voted ≥ 7 (from 1, totally disagree, to 10, totally agree). RESULTS: Three overarching principles and 17 recommendations were generated. All reached agreement. According to them, axSpA care should be holistic and individualized, taking into account objective findings, comorbidities, and patients' opinions and preferences. Integrating imaging and clinical assessment with biomarker analysis could also help in decision-making. Connected to treatments, in refractory enthesitis, b/tsDMARDs are recommended. If active peripheral arthritis, csDMARD might be considered before b/tsDMARDs. The presence of significant structural damage, long disease duration, or HLA-B27-negative status do not contraindicate for the use of b/tsDMARDs. CONCLUSIONS: These recommendations are intended to complement guidelines by helping health professionals address and manage specific groups of patients, particular clinical scenarios, and gaps in axSpA.

Real-World Effectiveness and Treatment Retention of Secukinumab in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: A Descriptive Observational Analysis of the Spanish BIOBADASER Registry.

Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.

Disease activity indexes might not capture the same disease aspects in males and females with ankylosing spondylitis: A real-world nationwide analysis.

Background: To evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS). Methods: Ancillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was "disease control" assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender. Results: We analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02). Conclusion: This study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.

Changes in the use patterns of bDMARDs in patients with rheumatic diseases over the past 13 years.

The better understanding of the safety of biologic DMARDs (bDMARDs), as well as the emergence of new bDMARDs against different therapeutic targets and biosimilars have likely influenced the use patterns of these compounds over time. The aim of this study is to assess changes in demographic characteristics, disease activity and treatment patterns in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who started a first- or second-line biologic between 2007 and mid-2020. Patients diagnosed with RA, PsA or AS included in the BIOBADASER registry from January 2007 to July 2020 were included. According to the start date of a first- or second-line biologic therapy, patients were stratified into four time periods: 2007-2009; 2010-2013; 2014-2017; 2018-2020 and analyzed cross-sectionally in each period. Demographic and clinical variables, as well as the type of biologic used, were assessed. Generalized linear models were applied to study the evolution of the variables of interest over time periods, the diagnosis, and the interactions between them. A total of 4543 patients initiated a first biologic during the entire time frame of the study. Over the four time periods, disease evolution at the time of biologic initiation (p < 0.001), disease activity (p < 0.001), retention rate (p < 0.001) and the use of tumor necrosis factor inhibitors as a first-line treatment (p < 0.001) showed a significant tendency to decrease. Conversely, comorbidities, as assessed by the Charlson index (p < 0.001), and the percentage of patients using bDMARDs in monotherapy (p < 0.001), and corticosteroids (p < 0.001) tended to increase over time. Over the entire period of the study's analysis, 3289 patients started a second biologic. The following trends were observed: decreased DAS28 at switching (p < 0.001), lower retention rates (p = 0.004), and incremental changes to the therapeutic target between the first and second biologic (p < 0.001). From 2007 until now rheumatic patients who started a biologic were older, exhibited less clinical activity, presented more comorbidities, and switched to a different biologic more frequently and earlier.

Association of apolipoprotein B/apolipoprotein A1 ratio and cardiovascular events in rheumatoid arthritis: results of the CARMA study.

OBJECTIVES: To assess the plasma apolipoprotein B/apolipoprotein A1 ratio and its potential association with cardiovascular events (CVE) in patients with rheumatoid arthritis (RA). METHODS: A baseline analysis was made of the CARdiovascular in rheuMAtology Project (CARMA), a 10-year prospective study evaluating the presence of at least one CVE in 775 Spanish patients with RA. Of them, 29 had already experienced CVE prior to the inclusion in the study. We assessed the association between the elevation of the apoB/apoA1 ratio with the presence of CVE according to a logistic regression model for possible confounding factors. We also analysed the main parameters of activity of RA and parameters related to lipid metabolism. RA patients were classified according to treatment: patients treated with disease-modifying anti-rheumatic drugs without biologics and those undergoing biologic therapy (anti-TNF-α, anti-IL-6 receptor, and other biologic agents). RESULTS: The apoB/apoA1 ratio of patients who had experienced CVE was higher than that of patients without previous CVE (0.65 vs. 0.60). However, the difference between both subgroups did not reach statistical significance (p=0.197). It was also the case after the multivariate analysis [OR: 1.48 (95% CI: 0.15-14.4); p=0.735]. RA patients from the group with CVE were more commonly receiving lipid-lowering treatment with statins than those without CVE history (41.4% vs. 20%, p=0.005). High HAQ and high atherogenic index were significantly associated with the presence of CVE. There was no statistical association between the type of biologic therapy used in RA and the presence of CVE. CONCLUSIONS: No association between ApoB/apoA1 ratio and CVE was found at the baseline visit of patients with RA from the CARMA study.

Magnetic resonance imaging assessment in patients with axial spondyloarthritis: development of checklists for use in clinical practice.

The objective of our study was to standardize magnetic resonance imaging (MRI) assessment of spine and sacroiliac joints in patients with axial spondyloarthritis (axSpA) and/or inflammatory spinal pain, by creating checklists and templates based on the opinions of rheumatologists and radiologists. A scientific committee developed a series of questionnaires with multiple items regarding MRI in patients with axial inflammatory pain and/or axSpA. Then an expert panel of rheumatologists and radiologists rated all items in a 9-point Likert scale. Finally, the scientific committee and the expert panel met to create the definitive documents. Several definitive checklists and templates were generated for rheumatologist-requested MRI and for radiologist-requested MRI reports of sacroiliac joint and spinal examinations. A technical requirement protocol was also agreed on. Our results could be useful in increasing understanding between rheumatologists and radiologists regarding MRI in axSpA diagnosis and follow-up.

Relationship between fecal calprotectin, anti-Saccharomyces cerevisiae antibodies and other markers of disease activity in patients with spondyloarthritis. / Relación de calprotectina fecal y anti saccharomyces antisacaromices con otros marcadores de actividad en pacientes con espondiloartritis.

OBJECTIVE: To assess the relationship between the increase of fecal calprotectin, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease markers in a group of patients with spondyloarthritis. METHODS: We evaluated patients who were at least 18-years-old and met the Assessment in Spondyloarthritis International Society (ASAS) criteria for spondyloarthritis or the New York modified criteria. We analyzed activity criteria, physical function, analytical criteria (human leukocyte antigen [HLA] B27, fecal calprotectin, presence of ASCA, among others) and demographic data. RESULTS: We included 33 patients. All but one patient had normal ASCA values. We found statistical significance in the correlation of calprotectin with C-reactive protein (CRP) but not with other parameters. We also found a relationship between calprotectin levels and nonsteroidal anti-inflammatory drug (NSAID) intake (P=.001). We found no relationship between CRP levels and NSAID use. After discontinuation of NSAIDs for one month, we found no significant differences in calprotectin levels (P=.9). CONCLUSION: Fecal calprotectin is elevated in patients with spondyloarthritis and correlates positively with CRP. Level of fecal calprotectin is not altered by NSAID use. The amount of ASCA present does not change and does not correlate with any clinical parameters in the study population.

Spanish Registry of Recent-onset Psoriatic Arthritis (REAPSER study): Aims and methodology. / Registro Español de Artritis Psoriásica de Reciente Comienzo (estudio REAPSER). Objetivos y metodología.

AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis.

Different clinical expression of patients with ankylosing spondylitis according to gender in relation to time since onset of disease. Data from REGISPONSER.

OBJECTIVE: To describe the differential characteristics by gender and time since disease onset in patients diagnosed with ankylosing spondylitis (AS) attending the Spanish rheumatology clinics, including those on the "Spanish Registry of spondyloarthritis" (REGISPONSER), as well as the diagnostic and therapeutic implications that this entails. PATIENTS AND METHODS: This is a transversal and observational study of 1514 patients with AS selected from 2367 spondyloarthritis cases included in REGISPONSER. For each patient, the demographics, epidemiology, geriatric, clinical, laboratory, radiological, and therapeutic aspects were were evaluated and comprehensively recorded under the aegis of REGISPONSER, constituting the Minimum Basic identifying data for the disease. Physical function was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI). Clinical activity was evaluated using erythrocyte sedimentation rate, C reactive protein and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Each patient underwent pelvic anteroposterior, anteroposterior and lateral lumbar spine as well as lateral cervical spine x rays; they were scored according to the Bath Ankylosing Spondylitis Spine Radiographic Index, which measures structural damage. RESULTS: Of the 1514 patients screened, 1131 (74.7%) were men. We found significant differences in age at onset of symptoms as well as in the day of inclusion, between the two groups, being lower in men. We also obtained differences in the duration of the disease, which was lower in women. As for the existence of a history of AS among first-degree relatives, family forms were more common among women. The mean BASDAI score was also higher in women, regardless of time since onset of disease. In contrast, the improvement of pain with the use of NSAID's and radiological severity were higher in men, both reaching statistical significance. CONCLUSIONS: Among the Spanish AS patients, there are some differences in the clinical manifestations, even when the time since onset of disease was controlled; we also found radiological differences by gender; men showing more structural damage, while women were more active. These data suggest that the phenotype of AS differs between genders. This can influence the subsequent diagnostic approach and therapeutic decisions.