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Article ; Online: Biological DMARDs and disease modification in axial spondyloarthritis

Sofia Ramiro / Alexandre Sepriano

RMD Open, Vol 7, Iss

a review through the lens of causal inference

2021 Volume 2

Abstract: Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is ... ...

Abstract	Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Available therapeutic options include biological disease-modifying antirheumatic drugs (bDMARDs), which have been proven effective in suppressing inflammation in several randomised controlled trials (RCT), the gold standard for evaluating causal treatment effects. RCTs are, however, unfeasible for testing structural effects in axSpA mainly due to the low sensitivity to change of the mSASSS. The available literature therefore mainly includes observational research, which poses serious challenges to the determination of causality. Here, we review the studies testing the effect of bDMARDs on spinal radiographic progression, making use of the principles of causal inference. By exploring the assumptions of causality under counterfactual reasoning (exchangeability, positivity and consistency), we distinguish between studies that likely have reported confounded treatment effects and studies that, on the basis of their design, have more likely reported causal treatment effects. We conclude that bDMARDs might, indirectly, interfere with spinal radiographic progression in axSpA by their effect on inflammation. Innovations in imaging are expected, so that placebo-controlled trials can in the future become a reality. In the meantime, causal inference analysis using observational data may contribute to a better understanding of whether disease modification is possible in axSpA.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mentoring for postdoctoral researchers in rheumatology

Sofia Ramiro / Jan Leipe / Polina Putrik / Alexandre Sepriano / James Gwinnutt

RMD Open, Vol 6, Iss

the Emerging EULAR Network (EMEUNET) post-doc mentoring programme

2020 Volume 1

Abstract: ObjectiveThis study aims to (1) assess the perceived need for a postdoctoral (post-doc) mentoring programme in rheumatology, (2) describe the characteristics and organisational aspects of a pilot mentoring programme implemented by the EMerging European ... ...

Abstract	ObjectiveThis study aims to (1) assess the perceived need for a postdoctoral (post-doc) mentoring programme in rheumatology, (2) describe the characteristics and organisational aspects of a pilot mentoring programme implemented by the EMerging European League Against Rheumatism NETwork (EMEUNET) and (3) report mentors’ and mentees’ evaluation of the pilot programme.MethodsAn online survey was conducted among young researchers in rheumatology to evaluate the need and preferred characteristics of a post-doc mentoring initiative. Informed by the survey, a pilot programme was designed and launched. The pilot programme was evaluated with 3-month, 6-moth and 12-month surveys and interviews with mentees and a 12-month survey among mentors, after completion.ResultsFrom 275 responses (43 countries, 86% from Europe) collected, analyses were restricted to the target population (total population=158; post-docs (n=103 (65%)) and PhD students (n=55 (35%))). There was a clear need (99% positive responses) for a post-doc mentoring programme. Discussions about current and new projects, and how to lead projects were ranked as priorities in post-doc mentoring. The most desired mentor attribute was generosity and interest in helping (86%), followed by research experience (68%) and having a well-established network (66%). The pilot programme included four mentees (through competitive application) allocated to three mentors. Evaluation surveys and interviews revealed that the programme organisation and content were well appreciated by mentees and mentors.ConclusionsThe EMEUNET post-doc mentoring programme addresses unmet need for mentoring, is viable and appreciated by mentors and mentees. The programme structure and content are transferable to other fields where there is need for academic career mentoring.
Keywords	Medicine ; R
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 5-year follow-up of spinal and sacroiliac MRI abnormalities in early axial spondyloarthritis

Anna Molto / Pascal Claudepierre / Alexandre Sepriano / Floris A van Gaalen / Queeny Madari / Daniel Wendling

RMD Open, Vol 6, Iss

data from the DESIR cohort

2020 Volume 1

Abstract: ObjectiveTo study changes on MRI of the spine and sacroiliac joint (SIJ) in early axial spondyloarthritis (axSpA) over time.MethodsIn the Devenir des Spondyloarthropathies Indifférenciées Récentes cohort, MRI-spine and MRI-SIJ at baseline and 2 and 5 ... ...

Abstract	ObjectiveTo study changes on MRI of the spine and sacroiliac joint (SIJ) in early axial spondyloarthritis (axSpA) over time.MethodsIn the Devenir des Spondyloarthropathies Indifférenciées Récentes cohort, MRI-spine and MRI-SIJ at baseline and 2 and 5 years were scored by central readers for bone marrow oedema (BME), fatty lesions, erosions, sclerosis, ankylosis and spinal bone spurs. The average mean number of lesions was reported or the agreement of ≥2 out of 3 readers for binary outcomes. Net progression was calculated by subtracting the patients that ‘improved’ from those that ‘worsened’ divided by the total number of patients.ResultsOver 5 years, in 155 patients with axSpA (mean age 33.5 (SD 8.9) years, symptom duration 1.4 (0.8) years, 63% human leucocyte antigen+, 14% modified New York+), BME on MRI-SIJ decreased by a mean Spondyloarthritis Research Consortium of Canada score of 1.4 (SD 6.5) (p=0.009). The largest BME decrease was observed in patients using biological disease-modifying antirheumatic drugs at 5 years. Spinal BME increased by 0.3 (4.6) (p=0.41). Fatty lesions and/or erosions on MRI-SIJ increased by a mean of 1.0 (SD 2.6) (p<0.001). Spinal fatty lesions and/or erosions increased by 0.2 (SD 0.5) (p<0.001). Compared with baseline, at 5 years, 7.3% less patients had BME on MRI-SIJ according to the Assessment of Spondyloarthritis International Society definition, while 6.6% more patients had ≥5 fatty lesions and/or erosions. At 5 years, 0.7% less patients had ≥5 spinal BME lesions and 0.7% less patients had ≥5 spinal fatty lesions.ConclusionOver 5 years, BME on MRI-SIJ decreased and spinal BME remained similar, but numerically, little progression of structural lesions on MRI of the SIJ and spine was seen.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Do fatty lesions explain the effect of inflammation on new syndesmophytes in patients with radiographic axial spondyloarthritis? Results from the SIAS cohort and ASSERT trial

Sofia Ramiro / Robert Landewé / Désirée van der Heijde / Xenofon Baraliakos / Monique Reijnierse / Juergen Braun / Pedro M Machado / Alexandre Sepriano / Floris A van Gaalen / Rosaline van den Berg / Rosalinde Stal

RMD Open, Vol 9, Iss

2023 Volume 3

Abstract: Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive ...

Abstract	Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition.Results Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition.Conclusion In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2023-08-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distinction and prognosis of early arthritis phenotypes

Sofia Ramiro / Robert Landewé / Annette van der Helm-van Mil / Alexandre Sepriano / Bernard Combe / Alison Kent / Dirkjan van Schaardenburg / Bastiaan van Dijk / Elsa Mateus

RMD Open, Vol 9, Iss

an analysis in three European cohorts

2023 Volume 4

Abstract: Objectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade, Etude et Suivi des Polyarthrites Indifférenciées Récentes ( ... ...

Abstract	Objectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade, Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) and Early Arthritis Clinic (EAC)) were analysed. Clinical data were collected up to 24 years. Hands and feet radiographs were scored according to the Sharp van der Heijde (SvdH) method. Latent class analysis was applied to determine the EA phenotypes at baseline. Each class received a label reflecting its most prominent features. Prognostic outcomes included Health Assessment Questionnaire (HAQ), Short Form 36 (SF36) and SvdH score. The association between class membership and outcomes over time was tested in multivariable models.Results In total, 390 (Reade), 798 (ESPOIR) and 3991 (EAC) patients were analysed separately. Two classes with symmetrical polyarthritis emerged; one of these labelled as autoimmune inflammatory polyarthritis (AIPA), had high likelihood of acute phase reactants (APR) elevation and autoantibody positivity, while the other (mild-inflammatory polyarthritis; MIPA) had not. A third class had oligoarthritis of upper limbs (OAUL) and could be subdivided into autoimmune OAUL and mild-inflammatory OAUL. A fifth class had oligoarthritis of lower limbs. The SvdH scores were worse in patients with APR/autoantibodies (AIPA) than in those without (MIPA). No clinically meaningful differences across classes in HAQ or SF36 over time were found.Conclusion Radiographic progression over time primarily occurs in EA patients with APR/autoantibodies. The absence of these markers, however, does not necessarily translate into better long-term function and quality of life. Clinicians should not only aim at preventing joint damage, but look beyond structural progression in order to further improve the lives of people with EA.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Investigator initiated trials in Portuguese rheumatology

Elsa Vieira_Sousa / Alexandre Sepriano / Fernando Pimentel_Santos

Acta Reumatológica Portuguesa, Vol 2016, Iss 2, Pp 101-

2016 Volume 103

Keywords	Internal medicine ; RC31-1245 ; Immunologic diseases. Allergy ; RC581-607
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	Sociedade Portuguesa de Reumatologia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of vertebral corner inflammation and fat deposition on MRI on syndesmophyte development detected on whole spine low-dose CT scan in radiographic axial spondyloarthritis

Sofia Ramiro / Robert Landewé / Désirée van der Heijde / Xenofon Baraliakos / Monique Reijnierse / Alexandre Sepriano / Floris van Gaalen / Rosaline van den Berg / Rosalinde Stal

RMD Open, Vol 8, Iss

2022 Volume 2

Abstract: Objectives To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth.Methods Patients from the ... ...

Abstract	Objectives To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth.Methods Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort underwent MRI (baseline, 1 year and 2 years) and ldCT (baseline and 2 years). MR images were scored by three readers for VCI and VCFD, MRI patterns were defined by presence of VCI and/or VCFD over 2 years. LdCT images were scored by two central readers for presence and size of syndesmophytes and change was calculated for new or new/grown syndesmophytes. Multilevel generalised estimated equations were used to test the associations between VCI and VCFD and syndesmophyte development.Results Fifty radiographic patients with axial spondyloarthritis were included (mean age 49 years, 86% male, 78% HLA-B27+). Absence of both VCI and VCFD protected against syndesmophyte development (ORs 0.36–0.37). Presence of VCI and/or VCFD increased the risk of syndesmophyte development (ORs 1.73–2.60). Out of all corners with a new or new/grown syndesmophyte, 47% of corners according to reader 1 and 44% according to reader 2 had neither VCI nor VCFD preceding the bone formation.Conclusions VCI and VCFD were positively associated with syndesmophyte development. This has been shown for the first time for syndesmophytes detected on ldCT and also in the thoracic spine. However, almost half of all bone formation occurred in corners without VCI or VCFD, suggesting the presence of these lesions in yearly MRIs does not fully clarify the development of syndesmophytes.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lumbar myofascial physical properties in healthy adults

Fernando Pimentel-Santos / Santiago Rodrigues Manica / Alfonse T Masi / João Lagoas-Gomes / Mariana Baptista Santos / Sofia Ramiro / Alexandre Sepriano / Kalyani Nair / Patrícia Gomes-Alves / Júlia Costa / Jaime C Branco

Acta Reumatológica Portuguesa, Vol 2021, Iss 2, Pp 110-

myotonometry vs. shear wave elastography measurements

2021 Volume 119

Abstract: Objective: The human resting myofascial tone maintains the body tone in a neutral posture, the assessment of this and other muscle physical properties (MPP) is relevant, since, it is altered in many pathological states. Patients and methods: Seventeen ... ...

Abstract	Objective: The human resting myofascial tone maintains the body tone in a neutral posture, the assessment of this and other muscle physical properties (MPP) is relevant, since, it is altered in many pathological states. Patients and methods: Seventeen healthy subjects (8 males), between 18-50 years old, were assessed. The MPP of lower lumbar muscles was evaluated on right and left sides during prone resting position using two devices; myotonometry (stiffness, elasticity and tone) and ultrasound-based shear-wave elastography (SWE) (shear modulus). MTM measurements were performed at two anatomic points (ANp), selected by an experienced reader and at an adjacent ultra-sound determined point (USp). Myotonometry measurements of the erector spinae and SWE measurements of multifidus muscles at the L3-4 level were compared between genders and sides. The intra-reader reliability (IRR) for each device and correlations between techniques were analysed. MTM measurements performed at ANp and USp were compared. The intraclass correlation coefficient (ICC) was assessed for both devices. Correlations between stiffness (myotonometry) and shear modulus (SWE) at the respective muscle depths were assessed with Spearman correlation. Results: Males had greater stiffness and tone than females, particularly on the dominant side. MPP assessed by myotonometry were not different between ANp and USp. Good/Excellent IRR was documented for measurements by MTM (ICC≥0.90) and SWE (ICC≥0.85). No correlation in myotonometry stiffness and SWE shear modulus was found. For myotonometry assessments, the addition of ultrasonography was not different from anatomic localizations. No correlation of measurements was found between devices assessing respective L3-4 level muscles. Conclusions: Gender and side differences must be considered when assessing MPP in axial muscles. For MTM assessments, the addition of ultrasonography was not different to anatomic references. No correlation was found between devices.
Keywords	human resting myofascial tone (hrmt) ; myotonometry ; elastography ; myofascial physical properties ; Internal medicine ; RC31-1245 ; Immunologic diseases. Allergy ; RC581-607
Subject code	796
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Sociedade Portuguesa de Reumatologia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The European Portuguese version of the ASAS Health Index for Patients with Spondyloarthritis

Santiago Rodrigues-Manica / Eduardo Cruz / Sofia Ramiro / Sandra Sousa / Renata Aguiar / Alexandre Sepriano / Pedro Machado / Jaime Branco / Uta Kiltz / Fernando Pimentel-Santos

Acta Reumatológica Portuguesa, Vol 2020, Iss 1, Pp 26-

Measurement properties

2020 Volume 33

Abstract: OBJECTIVE: The Assessments of SpondyloArthritis international Society Health Index (ASAS HI), estimates the impact of Spondyloarthritis (SpA) on global functioning and health. This article assesses the construct validity, reliability and responsiveness ... ...

Abstract	OBJECTIVE: The Assessments of SpondyloArthritis international Society Health Index (ASAS HI), estimates the impact of Spondyloarthritis (SpA) on global functioning and health. This article assesses the construct validity, reliability and responsiveness of the Portuguese version of the ASAS HI. PATIENTS AND METHODS: Patients fulfilling ASAS classification criteria for axial (axSpA) or peripheral SpA (pSpA) were included. Construct validity was assessed through Spearman’s correlation analysis with other health outcomes. Discriminant validity was tested comparing the ASAS HI across disease activity and functional states using the Kruskal–Wallis test. Internal consistency was assessed by Cronbach’s α, and test-retest reliability by intraclass correlation coefficients (ICC). Responsiveness was evaluated by the standardized response mean (SRM) in patients with active disease who required therapy escalation. RESULTS: Among the 91 patients included, 67% were male, mean (SD) age 47.2 (12.9) years, 63 patients with axSpA and 28 patients with pSpA. The hypothesis defined a priori to test construct validity were confirmed. The ASAS HI showed ability to discriminate between patients with different disease activity and functional states (p
Keywords	patient-reported outcome measure ; patient reported outcomes ; quality of life ; spondyloarthritis ; Internal medicine ; RC31-1245 ; Immunologic diseases. Allergy ; RC581-607
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Sociedade Portuguesa de Reumatologia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cervical Spine Involvement as Initial Manifestation of Rheumatoid Arthritis

Filipe Araújo / Inês Silva / Alexandre Sepriano / Carla Reizinho / Luís Marques / Patrícia Nero / Jaime Cunha Branco

Acta Reumatológica Portuguesa, Vol 2015, Iss 1, Pp 64-

a case report

2015 Volume 67

Abstract: Rheumatoid arthritis’ synovitis affects mostly small hand and feet joints, although it may compromise any joint with a synovial lining. Cervical involvement occurs usually in longstanding disease in over half of these patients. We report the case of a 35- ...

Abstract	Rheumatoid arthritis’ synovitis affects mostly small hand and feet joints, although it may compromise any joint with a synovial lining. Cervical involvement occurs usually in longstanding disease in over half of these patients. We report the case of a 35-year old male patient who was referred to our outpatient clinic for a 2-year severe and disabling inflammatory neck pain, with incomplete response to intramuscular non-steroidal anti-inflammatory drugs and unremarkable cervical imaging studies. He also mentioned self-limited episodes of symmetric polyarthralgia involving hands, wrists, elbows, knees and feet, which started after his cervical complaints. On laboratorial workup, positive rheumatoid factor and anti-citrullinated peptide antibody and negative HLA-B27 were found. Cervical spine magnetic resonance imaging revealed atlantoaxial subluxation and odontoid process inflammatory pannus and erosions. Rheumatoid arthritis with cervical spine involvement as initial manifestation of disease was the definite diagnosis. The patient was started on methotrexate and prednisone and he was referred to neurosurgery outpatient clinic for cervical spine fixation.
Keywords	rheumatoid arthritis ; cervical spine ; inflammatory pannus ; atlantoaxial subluxation ; Internal medicine ; RC31-1245 ; Immunologic diseases. Allergy ; RC581-607
Subject code	610
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Sociedade Portuguesa de Reumatologia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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